العنوان البديل: Hypoxic postconditioning protects myocardium by regulating autophagy in aging cardiomyocytes through piRNA-005854.

المؤلفون: 迟宏扬^1,2, 杨慧霞^1,2, 郝银菊³, 杨安宁^2,4, 白志刚^2,5, 焦 运^2,6, 熊建团^2,4, 马胜超^2,4, 姜怡邓^2,4

المصدر: Chinese Journal of Tissue Engineering Research / Zhongguo Zuzhi Gongcheng Yanjiu. 5/8/2024, Vol. 28 Issue 13, p2054-2060. 7p.

مصطلحات موضوعية: *LACTATE dehydrogenase, *ISCHEMIC postconditioning, *REPERFUSION injury, *MYOCARDIAL injury, *WESTERN immunoblotting, *GALACTOSE, *CREATINE kinase

الملخص (بالإنجليزية): BACKGROUND: Ischemic postconditioning is one of the effective ways to reduce ischemia-reperfusion injury and has been more and more widely used in clinical practice in recent years, but its specific molecular mechanism has yet to be studied. OBJECTIVE: To investigate the role and mechanism of piRNA-005854 in the aging cardiomyocytes caused by hypoxic postconditioning. METHODS: In vitro, cardiomyocytes were administered 8 mg/mL D-galactose for 9 days to induce their aging. β-Galactosidase staining was used to observe the aging of cardiomyocytes. Senescent cells were treated with hypoxia/reoxygenation and hypoxic postconditioning. ELISA was utilized to detect changes in myocardial injury markers creatine kinase isoenzyme MB and lactate dehydrogenase levels. Western blot assay was applied to detect the expression changes of autophagy-related proteins LC3II, p62, ULK1 and phosphorylated ULK1 in aging cardiomyocytes. qRT-PCR was employed to determine the expression level of piRNA-005854. piRNA-005854 inhibitor and piRNA-005854 mimics were transferred into aging cardiomyocytes and followed with hypoxic postconditioning. Western blot assay was used to examine the expression of LC3II, p62, ULK1 and phosphorylated ULK1. RESULTS AND CONCLUSION: (1) D-galactose induced obvious senescence of cardiomyocytes 9 days later. (2) Compared with the normoxia group, creatine kinase isoenzyme MB and lactate dehydrogenase levels increased in the hypoxia/reoxygenation group (P < 0.01); LC3 II/I expression was increased; p62 expression was decreased; ULK1 phosphorylation level was increased, and piRNA-005854 expression was increased (P < 0.01). (3) Compared with the hypoxia/ reoxygenation group, creatine kinase isoenzyme MB and lactate dehydrogenase levels significantly reduced in the hypoxic postconditioning group (P < 0.01); LC3 II/I expression significantly decreased (P < 0.05); p62 expression increased (P < 0.01); ULK1 phosphorylation level decreased (P < 0.05), and piRNA-005854 expression decreased (P < 0.01). (4) After transfection of piRNA-005854 inhibitor, LC3II/I expression was decreased (P < 0.01); the expression of p62 was increased significantly (P < 0.05); the phosphorylation level of ULK1 was decreased significantly (P < 0.01). After transfection of piRNA-005854 mimics, LC3II/ I expression was increased significantly; the expression of p62 was decreased, and the phosphorylation level of ULK1 was increased significantly (P < 0.01). (5) The results show that piRNA-005854-mediated reduction of ULK1-dependent autophagy level is a possible mechanism that hypoxic postconditioning exerts its protective effect on aging cardiomyocytes. [ABSTRACT FROM AUTHOR]

Abstract (Chinese): 背景：缺血后处理是减轻缺血再灌注损伤的有效方式之一, 近年来被越来越广泛地应用于临床实践, 但其具体分子机制还有待研究。 目的：探讨piRNA-005854在衰老心肌细胞缺氧后处理中的作用及机制。 方法：体外给予心肌细胞8 mg/mL D-半乳糖9 d诱导其衰老, β-半乳糖苷酶染色观察心肌细胞的衰老情况；衰老后细胞给予缺氧/复氧处 理和缺氧后处理, ELISA检测心肌损伤标志物肌酸激酶同工酶MB以及乳酸脱氢酶水平；Western blot检测衰老心肌细胞中自噬相关蛋白 LC3Ⅱ、p62和ULK1及其磷酸化ULK1的表达；qRT-PCR检测piRNA-005854的表达水平；进一步用piRNA-005854 inhibitor及piRNA-005854 mimics 转染衰老心肌细胞并进行缺氧后处理, Western blot检测LC3Ⅱ、p62和ULK1及其磷酸化ULK1的表达。 结果与结论：①D-半乳糖诱导9 d后心肌细胞出现明显衰老；②与正常氧组比较, 缺氧/复氧组肌酸激酶同工酶MB以及乳酸脱氢酶水平增 加(P < 0.01)；LC3Ⅱ/Ⅰ表达升高、p62表达降低、ULK1磷酸化水平升高、piRNA-005854表达升高(P < 0.01)；③与缺氧/复氧组比较, 缺氧后 处理组肌酸激酶同工酶MB以及乳酸脱氢酶水平明显减少(P < 0.01)；LC3Ⅱ/Ⅰ表达明显降低(P < 0.05)、p62表达升高(P < 0.01)、ULK1磷酸化 水平降低(P < 0.05)、piRNA-005854表达降低(P < 0.01)；④转染piRNA-005854 inhibitor后, LC3Ⅱ/Ⅰ表达降低(P < 0.01), p62表达明显升高(P < 0.05), ULK1磷酸化水平明显降低(P < 0.01)；转染piRNA-005854 mimics后, LC3Ⅱ/Ⅰ表达显著升高, p62表达降低, ULK1磷酸化水平明显增 加(P < 0.01)；⑤结果表明, piRNA-005854介导的ULK1依赖性自噬水平降低是衰老心肌细胞缺氧后处理发挥保护作用的可能机制。 [ABSTRACT FROM AUTHOR]

العنوان البديل: Role of LncRNA MALAT1 in myocardial autophagy reduction in aging rats after ischemic postconditioning.

المؤلفون: 杨慧霞^1,2, 揭育祯^1,2, 白志刚^2,3, 焦 运^2,4, 杨 勇^2,3, 马天龙^2,5, 马胜超^2,5, 姜怡邓^2,5

المصدر: Chinese Journal of Tissue Engineering Research / Zhongguo Zuzhi Gongcheng Yanjiu. 7/18/2023, Vol. 27 Issue 20, p3173-3179. 7p.

مصطلحات موضوعية: *LINCRNA, *ISCHEMIC postconditioning, *SPRAGUE Dawley rats, *REPERFUSION injury, *PROTEIN expression

الملخص (بالإنجليزية): BACKGROUND: Ischemic postconditioning can alleviate myocardial ischemia-reperfusion injury, but the specific mechanism is not clear. OBJECTIVE: To investigate the mechanism of long non-coding RNA (lncRNA) MALAT1 in the reduction of autophagy levels in aging myocardium induced by ischemic postconditioning. METHODS: Twenty-seven Sprague-Dawley rats aged 22-24 months were randomly divided into three groups, with nine rats in each group: sham operation, ischemia-reperfusion, and ischemic postconditioning groups. Morphological changes of myocardial tissue were observed by hematoxylin-eosin staining and Masson staining. Rat myocardial cells (H9C2) were induced in vitro with 8 mg/mL D-galactose for 9 days and then divided into normoxia, hypoxia-reoxygenation, and hypoxia postconditioning groups. Western blot was used to detect the protein expression levels of LC3II/I and p62. Fluorescence quantitative PCR was used to detect the expression of lncRNA MALAT1 in aging myocardium and aging cardiomyocytes. Autophagy double-labeled adenovirus (RFP-GFP-LC3) was used to observe the changes of autophagic flux in aging cardiomyocytes. lncRNA MALAT1 interference fragment and overexpression plasmid were transfected into aging cardiomyocytes and the protein expression levels of LC3II/I and p62 were detected by western blot. RESULTS AND CONCLUSION: Compared with the ischemia-reperfusion group, the myocardial tissue structure of the ischemic postconditioning group was basically clear, the nucleus was intact, and the deposition of blue collagen fibers in the myocardial tissue was reduced. Compared with the ischemia-reperfusion group, the expression of LC3II/I was decreased and the expression of p62 was increased in the ischemic postconditioning group (P < 0.05). Compared with the hypoxia-reperfusion group, the expression of LC3II/I was decreased (P < 0.01) and the expression of p62 was increased (P < 0.05) in the hypoxia postconditioning group, and the number of intracellular autophagosomes and autophagolysosomes was decreased (P < 0.05). Compared with the ischemiareperfusion group, the expression of MALAT1 in the aging myocardial tissue was decreased the ischemic postconditioning group (P < 0.01); compared with the hypoxia-reperfusion group, the expression of MALAT1 in aging cardiomyocytes was decreased in the hypoxic postconditioning group (P < 0.01). Compared with the hypoxia postconditioning+si-NC group, the expression of LC3II/I was decreased and the expression of p62 was increased in the hypoxia postconditioning +si-lncRNA MALAT1 (P < 0.01); compared with the hypoxia postconditioning+ad-NC group, the expression of LC3II/I was increased and the expression of p62 was decreased in the hypoxia postconditioning+ad-lncRNA MALAT1 group (P < 0.01). To conclude, the lncRNA MALAT1 mediated reduction of autophagy levels is an important mechanism underlying the protective effect of ischemic postconditioning in aging myocardium. [ABSTRACT FROM AUTHOR]

Abstract (Chinese): 背景：缺血后处理可缓解心肌缺血再灌注损伤，但是其具体机制尚不清楚。 目的：探讨lncRNA MALAT1在缺血后处理所引起衰老心肌自噬水平降低中的作用。 方法： 27只22-24月龄SD大鼠随机分为3组：假手术组、缺血再灌注组和缺血后处理组，每组9只，采用苏木精-伊红染色和Masson染色 观察心肌组织形态学变化； 体外使用8 mg/mL D-半乳糖诱导大鼠心肌(H9C2)细胞9 d后，分为正常氧组、缺氧复氧组和缺氧后处理组。 Western blot检测衰老心肌组织及衰老心肌细胞中LC3Ⅱ/Ⅰ和p62蛋白的表达；采用qRT-PCR检测衰老心肌组织和衰老心肌细胞中MALAT1相 对表达；转染自噬双标腺病毒(RFP-GFP-LC3)观察衰老心肌细胞自噬流的变化；衰老心肌细胞转染MALAT1干扰片段和过表达质粒，Western blot检测各组细胞中LC3Ⅱ/Ⅰ和p62蛋白的表达。 结果与结论： 与缺血再灌注组比较，缺血后处理组心肌组织结构基本清晰，细胞核完整，心肌组织间蓝色胶原纤维沉积减少； 与缺 血再灌注组比较，缺血后处理组LC3Ⅱ/Ⅰ表达降低且p62表达增高(P < 0.05)； 与缺氧复氧组比较，缺氧后处理组LC3Ⅱ/Ⅰ表达降低(P < 0.01)且p62表达增加(P < 0.05)，细胞内自噬体和自噬溶酶体数量均减少(P < 0.01)； 与缺血再灌注组比较，缺血后处理组衰老心肌组织的 MALAT1表达降低(P < 0.01)；与缺氧复氧组比较，缺氧后处理组衰老心肌细胞的MALAT1表达降低(P < 0.01)； 衰老心肌细胞转染MALAT1 干扰片段和过表达质粒后，与缺氧复氧+si-NC组比较，缺氧复氧+si-MALAT1组LC3Ⅱ/Ⅰ表达降低且p62表达增加(P < 0.01)；与缺氧后处理+ ad-NC组比较，缺氧后处理+ad-MALAT1组LC3Ⅱ/Ⅰ表达增加且p62表达降低(P < 0.01)； 结果表明：lncRNA MALAT1介导的自噬水平降低是 衰老大鼠心肌缺血后处理发挥保护作用的重要机制。 [ABSTRACT FROM AUTHOR]

المؤلفون: MAO Yikun, WANG Shilei, WU Xiuyun, ZHAO Qin, LI Yu

المصدر: 精准医学杂志, Vol 39, Iss 2, Pp 125-129 (2024)

مصطلحات موضوعية: sevoflurane, ischemic postconditioning, brain ischemia, reperfusion injury, nf-e2-related factor 2, signal transduction, rats, sprague-dawley, Medicine

الوصف: Objective To investigate the protective effect of sevoflurane postconditioning against cerebral ischemia/reperfusion (I/R) injury in rats and its mechanism of action. Methods A total of 80 specific pathogen-free healthy adult male Sprague-Dawley rats were selected and randomly divided into sham-operation group (S group), cerebral I/R group (I/R group), cerebral I/R+sevoflurane postconditioning group (ISP group), and cerebral I/R+sevoflurane postconditioning+nuclear factor ery-throid 2-related factor 2 (Nrf2) inhibitor group (ISPB group), with 20 rats in each group. All rats except those in the S group were used to establish a rat model of cerebral I/R injury using the suture method for occlusion of the middle cerebral artery for 2 h, followed by reperfusion for 24 h, and for the rats in the S group, threading was performed below the middle cerebral artery without ligation. The rats in the ISP group were given inhalation of 3% sevoflurane immediately after reperfusion for 30 min, and those in the ISPB group were given intraperitoneal injection of the Nrf2 inhibitor brusatol (2 mg/kg) at 30 min before ischemia in addition to the treatment in the ISP group. After successful modeling, neurological deficit score was used to eval-uate the degree of neurological impairment. Left ventricular blood samples and pathological sections of brain tissue were obtained, and 2,3,5-triphenyltetrazolium chloride staining was used to determine the percentage of cerebral infarct volume; enzyme-linked immunosorbent assay was used to measure the serum levels of inflammatory factors (interleukin-1β [IL-1β] and tumor necrosis factor-α [TNF-α]) and oxidative stress-related factors (malondialdehyde [MDA] and superoxide dismutase [SOD]); Western blotting was used to mea-sure the expression of apoptosis-related proteins (B-cell lymphoma-2 [Bcl-2], Bcl-2 related x [Bax], and Caspase-3) and Nrf2 signaling pathway-related proteins (Nrf2 and heme oxygenase-1 [HO-1]) in brain tissue; immunofluorescence assay was used to measure the expression of Nrf2 inside and outside the nucleus of brain tissue cells. Results Compared with the I/R group, the ISP group had significant reductions in neurological deficit score, the percentage of cerebral infarct volume, the serum levels of IL-1β, TNF-α, and MDA, and the levels of Bax and Caspase-3 in brain tissue (t=5.76-18.39,P

وصف الملف: electronic resource

العلاقة: https://jpmed.qdu.edu.cn/fileup/2096-529X/PDF/1716285328057-1573026655.pdfTest; https://doaj.org/toc/2096-529XTest

الوصول الحر: https://doaj.org/article/f83728471d6d43ad91e3718fd3c76a42Test

العنوان البديل: Ischemic post-conditioning inhibits lung ischemia/reperfusion-induced pyroptosis in rats via ROS-TXNIP-NLRP3-GSDMD pathway. (English)

المؤلفون: 王新雨, 徐俊鹏, 王肖婷, 宋正阳, 王万铁

المصدر: Chinese Journal of Pathophysiology; 2023, Vol. 39 Issue 6, p1005-1013, 9p

مصطلحات موضوعية: NLRP3 protein, THIOREDOXIN-interacting protein, ERYTHROCYTES, ISCHEMIC postconditioning, REACTIVE oxygen species

الملخص (بالإنجليزية): AIM: To evaluate the role of nucleotide-binding oligomerization domain-like receptor protein 3 （NLRP3） inflammasome-mediated pyroptosis in rat lung ischemia/reperfusion injury （LIRI） and the intervention effects of ischemic post-conditioning （I-post-C） treatment. METHODS: Twenty SPF grade male SD rats aged 6 to 8 weeks were randomly divided into 4 groups: control group, LIRI group, I-post-C group, and INF39+LIRI group. After the experiment, the rats were sacrificed, and tissue samples from the left lung were harvested. The morphological changes of the lung tissues were examined by ordinary light microscopy. The level of reactive oxygen species （ROS） was evaluated by dihydroethidium staining. The changes of oxidative stress indicators malondialdehyde（ MDA）, glutathione（ GSH） and myeloperoxidase（ MPO）, as well as the level of caspase-1, were detected using commercially available kits. The levels of interleukin-1β （IL-1β） and IL-18 in the lung tissue were detected by ELISA. The mRNA levels of NLRP3, IL-1β, IL-18 and thioredoxin-interacting protein （TXNIP） were detected by RT-qPCR. The protein levels of NLRP3, N-terminal fragment of gasdermin D （GSDMD-N）, cleaved caspase-1 and TXNIP were detected by Western blot. The TXNIP expression was also detected by immunofluorescence. RESULTS: The surface of the left lung in LIRI group was interspersed with dark red and light red, with brittle texture, obvious rupture of the alveolar wall, deformation and collapse of the alveoli, infiltration of neutrophils and red blood cells, and interstitial edema. The LIRI caused the production of a large number of ROS （P<0. 01）. Compared with control group, LIRI group showed significant increases in MDA content of and MPO activity, and a significant decrease in GSH content （P<0. 01）. The mRNA and protein levels of TXNIP were significantly up-regulated （P<0. 05）. The mRNA levels of IL-1β and IL-18 in the lung tissue were noticeably increased （P<0. 01）, and the mRNA and protein levels of NLRP3 were significantly increased （P<0. 05）. The protein levels of GSDMD-N and cleaved caspase-1 were significantly increased, and the activity of caspase-1 in the lung tissue was dramatically increased （P< 0. 01）. Compared with LIRI group, lung tissue injury in I-post-C group was significantly attenuated. The ROS accumulation was significantly reduced, the MDA content and MPO activity in I-post-C group were decreased （P<0. 05）, and the content of GSH was increased significantly （P<0. 01）. The mRNA and protein levels of TXNIP were down-regulated （P< 0. 05）. Compared with LIRI group, the mRNA level and tissue content of IL-1β and IL-18 in the lung tissue of I-post-C and INF39+LIRI groups were significantly decreased （P<0. 05）. The NLRP3 mRNA and protein levels in the lung tissue were significantly down-regulated, and the protein levels of GSDMD-N and cleaved caspase-1 were significantly decreased （P<0. 05）. CONCLUSION: The I-post-C alleviates LIRI in rats, and its mechanism may be related to the regulation of ROS-TXNIP-NLRP3-GSDMD signaling pathway. [ABSTRACT FROM AUTHOR]

Abstract (Chinese): 探讨核苷酸结合寡聚化结构域样受体蛋白3（nucleotide-binding oligomerization domain-like receptor protein 3, NLRP3）炎症小体介导的细胞焦亡在大鼠肺缺血/再灌注损伤（lung ischemia/reperfusion injury, LIRI）中的作用及缺血后处理（ischemic post-conditioning, I-post-C）的干预效果。方法: 将20只6~8周龄SPF级雄性 SD大鼠随机分为4组: 对照（control）组、LIRI组、I-post-C组和INF39（细胞焦亡抑制剂）+LIRI组。实验结束后处死大 鼠, 取左肺组织;普通光镜下观察肺组织形态;采用二氢乙啶染色评价肺组织活性氧簇（reactive oxygen species, ROS）水平;采用试剂盒检测肺组织氧化应激指标丙二醛（malondialdehyde, MDA）、谷胱甘肽（glutathione, GSH）和 髓过氧化物酶（myeloperoxidase, MPO）的变化及caspase-1活性;用ELISA 评估白细胞介素1β（interleukin-1β, IL- 1β）和IL-18水平;RT-qPCR检测NLRP3、IL-1β和IL-18的mRNA表达水平;Western blot检测NLRP3、gasdermin D N 端片段（N-terminal fragment of gasdermin D, GSDMD-N）、cleaved caspase-1和硫氧还蛋白相互作用蛋白（thioredoxininteracting protein, TXNIP）的蛋白水平;用免疫荧光染色法检测TXNIP的表达。结果: LIRI组肺组织表面呈暗红色 与淡红色相间, 质实较脆, 有明显的肺泡壁破裂、肺泡变形塌陷、中性粒细胞和红细胞浸润以及间质性水肿。与control组相比, LIRI引起大量ROS产生（P<0. 01）, LIRI组肺组织中MDA含量和MPO活性显著增加（P<0. 01）, GSH含 量显著减少（P<0. 01）, TXNIP的mRNA及蛋白表达显著上调（P<0. 05）, 肺组织中IL-1β和IL-18的mRNA及蛋白表 达显著增加（P<0. 01）, NLRP3的mRNA及蛋白水平显著上调（P<0. 05）, GSDMD-N和cleaved caspase-1的蛋白水平 显著升高（P<0. 01）。与LIRI组相比, I-post-C组肺组织损伤明显减轻, 肺组织中ROS的累积显著减少（P<0. 01）, MDA含量和MPO活性显著降低（P<0. 05）, GSH含量显著增加（P<0. 01）, TXNIP的mRNA及蛋白表达显著下调（P< 0. 05）。与LIRI组相比, I-post-C和INF39+LIRI组肺组织中IL-1β、IL-18和NLRP3的mRNA及蛋白水平显著降低（P< 0. 05）, GSDMD-N和cleaved caspase-1的蛋白水平显著降低（P<0. 05）。结论: 缺血/再灌注可激活细胞焦亡并引起 大鼠肺损伤, I-post-C可减轻大鼠LIRI, 其机制可能与ROS-TXNIP-NLRP3-GSDMD通路有关. [ABSTRACT FROM AUTHOR]

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المؤلفون: 张苗苗, 毛雯, 仝其广, 于海奕, 高炜

المساهمون: 煤炭总医院心内科, 北京,100028, 北京大学第三医院心内科

المصدر: CSCD ; 万方 ; http://d.g.wanfangdata.com.cn/Periodical_zhxxgb201607012.aspxTest

مصطلحات موضوعية: 心肌再灌注损伤, 缺血后适应, Myocardial reperfusion injury, Ischemic postconditioning

الوصف: 目的 探讨缺血后适应对在体大鼠缺血再灌注损伤后心肌梗死面积和血液动力学指标的影响及其机制.方法 将30只雄性SD大鼠按照随机数字表法分为假手术组、缺血再灌注组(IR组)和缺血后适应组(PC组),每组10只.通过结扎左冠状动脉前降支近段30 min,再灌注2h建立大鼠缺血再灌注模型(IR组).PC组为在再灌注开始瞬间实施再灌注30 s、缺血30 s,共3个循环,随后恢复再灌2h.通过颈动脉插管测定不同组大鼠的血液动力学指标;采用伊文思蓝和氯化三苯基四氮唑染色法测定缺血面积和梗死面积;分别通过Western blot和实时定量PCR检测各组大鼠再灌注2h缺血心肌预测的靶基因Bcl-2家族促凋亡蛋白之一Bim蛋白及微小RNA (miR)-214的表达水平.结果 (1)各组大鼠血液动力学的检测结果:IR组和PC组大鼠左心室收缩压(LVSP)、左心室内压最大上升速率(+dp/dtmax)及最大下降速率(-dp/dtmax)和心率均较假手术组低,左心室舒张末压(LVEDP)较假手术组高,差异均有统计学意义(P均＜0.05).PC组大鼠LVSP、+dp/dtmax和-dp/dtmax均较IR组高,LVEDP较IR组低,差异均有统计学意义(P均＜0.05).(2)各组大鼠心肌缺血和梗死范围的检测结果:PC组大鼠心肌缺血区面积(AAR)占左心室面积(LV)的比例(AAR/LV)与IP组比较差异无统计学意义[(27.00±7.55)％比(26.67±11.68)％,P＞0.05],梗死面积(IS)占AAR的比例(IS/AAR)则低于IR组[(30.67±3.51)％比(48.67±4.62)％,P＜0.05].(3)各组大鼠缺血心肌Bim蛋白表达的检测结果:IR组大鼠缺血区心肌组织中Bim蛋白表达水平高于假手术组(2.34 ±0.15比0.75 ±0.05,P＜0.05).PC组大鼠缺血区心肌组织中Bim蛋白表达水平则低于IR组(1.25 ±0.14比2.34 ±0.15,P＜0.05).(4)各组大鼠缺血心肌miR-214表达的检测结果:IR组大鼠缺血心肌组织中miR-214表达水平低于假手术组(0.20±0.04比1.00,P＜0.01),PC组大鼠缺血心肌组织中miR-214表达水平则高于IR组(0.85±0.20比0.20±0.04,P＜0.01),PC组与假手术组比较差异无统计学意义(P＞0.05).结论 缺血后适应处理可减少在体大鼠心肌梗死面积,改善缺血再灌注损伤后血液动力学,改善大鼠心肌缺血再灌注损伤.缺血后适应可降低Bim蛋白表达,Bim可能参与了缺血后适应的心肌保护作用,而其下调机制可能与miR-214表达升高有关. ; Objective This study is designed to observe the effect of ischemic postconditioning in rats underwent acute myocardial ischemia/reperfusion injury and to investigate the related mechanism.Methods A total of 30 SD rats were randomly divided into sham operation group (control group,n =10),ischemia/reperfusion group (IR group,n =10) and ischemic postconditioning group (PC group,n =10) based on random number table.Rats in IR group underwent 30 minutes myocardial ischemia by occlusion of the proximal portion of left anterior descending (LAD) coronary artery followed by 2 hours reperfusion.In control group,there was no IR intervention.In PC group,at the start of reperfusion,three cycles of 30 seconds reperfusion and 30 seconds LAD reocclusion preceded the 2 hours of reperfusion.The hemodynamic values were measured via a cannula inserted into the right common carotid artery.The area at risk was assessed by ...

العلاقة: 中华心血管病杂志.2016,44(7),616-620.; 1447259; http://hdl.handle.net/20.500.11897/494356Test

الإتاحة: https://doi.org/20.500.11897/494356Test
https://doi.org/10.3760/cma.j.issn.0253-3758.2016.07.012Test
https://hdl.handle.net/20.500.11897/494356Test

المؤلفون: Xiao-feng LAI, Kang-hua MA, Chun-chang QING, Zhen-yu ZHOU, Qiao WU

المصدر: Medical Journal of Chinese People's Liberation Army, Vol 36, Iss 8, Pp 808-812 (2011)

مصطلحات موضوعية: pharmacological postconditioning； ischemic postconditioning； ischemia-reperfusion； apoptosis, lcsh:R5-920, lcsh:R, lcsh:Medicine, lcsh:Medicine (General)

الوصف: Objective To compare the protective effect of insulin-like growth factor-1(IGF-1) and ischemic postconditioning on ischemia-reperfusion myocardium apoptosis,and explore the possible mechanisms of inhibition of apoptosis of myocardial cells.Methods Forty eight SD rats were randomly divided into 4 groups(12 each): sham-operation group(sham),ischemic/reperfusion group(I/R),ischemic postconditioning group(I-POST) and IGF-1 postconditioning group(IGF-1-POST).The rat model was established by repeated ligation.Except the sham group,rats in the other three groups subjected to 45min of ischemia followed by 120min of reperfusion.During the first 30min of the reperfusion period,the cardiac electrical activity was recorded.In the 120th minute of the reperfusion,the hemodynamic parameters were monitored.The serous TNF-α,IL-6 and IL-10 levels were detected by ELISA.The degree of myocardial damage was observed by HE staining.Apoptosis was detected by TUNEL,and the expressions of Pser-133-CREB and Bcl-2 protein were monitored by Western blotting and immunohistochemical methods.Results Compared with that in I/R group,the cardiac function of rats in I-POST group and IGF-1-POST group was improved;the serous TNF-α and IL-6 levels were lower while IL-10 level was higher;the elevation degree of ST segment,the ventricular premature beats and the duration of ventricular arrhythmia decreased at the same time;the degree of myocardial damage lessened and the number of apoptosis cells increased;the expressions of Pser-133-CREB and Bcl-2 protein increased significantly(P < 0.05).In comparison with the I-POST group,TNF-α decreased but IL-10 increased significantly in IGF-1-POST group(P < 0.05);the elevation degree of ST segment,the ventricular premature beats and the duration of ventricular arrhythmia increased significantly(P < 0.05).As the other aspects mentioned above,no statistical difference was found between the two groups(P > 0.05).Conclusions IGF-1 may play a protective effect on ischemia-reperfusion myocardium in a similar extent to that of ischemic postconditioning.The anti-apoptosis effect of IGF-1 and ischemic postconditioning may be related with the high expressions of Pser-133-CREB and t Bcl-2 protein.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doajarticles::5056ddc90dd493ef5964aa8e2160506dTest
http://www.plamj.org/index.php/plamj/article/view/192Test

المؤلفون: 程怡, 王强, 薛富善, 李瑞萍, 崔昕龙, 王世玉, 廖旭, 刘建华

المساهمون: 北京协和医学院,整形外科医院麻醉科,中国医学科学院,100144, 北京大学人民医院麻醉科

المصدر: 万方 ; http://d.g.wanfangdata.com.cn/Periodical_gwyx-mzxyfsfc201402004.aspxTest

مصطلحات موضوعية: 心肌缺血/再灌注损伤, 炎症反应, 迷走神经电刺激后处理, 肢体远隔缺血后处理, Myocardial ischemia/reperfusion injury, Inflammatory response, Vagal nerve electrical stimulation postconditioning, Limb remote ischemic postconditioning

الوصف: 目的 比较迷走神经电刺激后处理(postconditioning with vagus nerve electrical stimulation,POES)和肢体远隔缺血后处理(limb remote ischemic postconditioning,LRIPOC)对大鼠心肌缺血/再灌注损伤(ischemia/reperfusion injury,I/RI)中炎症反应的影响.方法 雄性SD大鼠80只,体重290 g～320 g,采用随机数字表法分为4组(每组20只):假手术组(S组)、缺血/再灌注(ischemia/reperfusion,I/R)组、POES组和LRIPOC组.监测I/R期间的心率(heart rate,HR)和平均动脉压(meanartery perssure,MAP),并计算HR和收缩压乘积(rate pressure product,RPP)作为心肌氧耗指数.各组随机取10只大鼠,于再灌注30、60 min和120 min时采集颈动脉血样,采用酶联免疫吸附测定法(enzyme-linked immunosorbent assay,ELISA)检测血清心肌肌钙蛋白Ⅰ(cardiac troponin Ⅰ,cTnⅠ)、肌酸激酶心肌型同工酶(myocardial-bound creatine kinase,CK-MB)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、高迁移率组蛋白1(high mobility group box i protein,HMGB-1)、细胞间黏附分子i(intercellular adhesion molecule-1,ICAM-1)、白介素(interleukin,IL)-1、IL-6和IL-10的浓度；于再灌注120 min颈动脉采血后,采用伊文蓝和氯化三苯基四氮唑双重染色法测定心肌梗死体积.各组随机取10只大鼠,于再灌注120 min处死后分别取缺血区和非缺血区心肌组织,采用ELISA法检测心肌TNF-α、HMGB-1、ICAM-1、IL-1、IL-6和IL-10的含量.结果 S组、I/R组、POES组和LRIPOC组的心肌梗死体积分别为0％、(72±9)％、(46±12)％和(57±9)％,血清cTnI浓度分别为(0.29±0.06)、(0.99±0.14)、(0.40±0.08) μg/L和(0.54±0.07)μg/L.与I/R组比较,POES组和LRIPOC组的心肌梗死体积、血清cTnI和CK-MB浓度,再灌注30 min和60 min时血清TNF-α浓度,再灌注120 min时血清、缺血区与非缺血区心肌组织内TNF-α、HMGB-1、ICAM-1、IL-1和IL-6的含量均显著降低,而POES组缺血区与非缺血区心肌组织内IL-10的含量则显著升高.与POES组比较,LRIPOC组的心肌梗死体积和血清cTnI浓度,再灌注60 min时血清TNF-α浓度、再灌注120 min时血清HMGB-1、ICAM-1、IL-1和IL-6的浓度,缺血区心肌组织内ICAM-1、IL-1和IL-6含量,非缺血区心肌组织内HMGB-1、ICAM-1、IL-1和IL-6含量均显著升高,而缺血区心肌组织内IL-10的含量则显著降低.结论 POES减轻大鼠心肌I/RI中炎症反应的作用强于LRIPOC,这可能是POES对心肌I/RI保护作用强于LRIPOC的原因之一. ; Objective To compare the effects of vagus nerve electrical stimulation postconditioning with limb remote ischemia postconditioning on inflammatory response during myocardial ischemia/reperfusion (I/R) in rat in vivo.Methods Eighty male Sprague-Dawley rats weighing 290 g-320 g were randomly allocated into four groups (n=20):sham (S) group,I/R group,postconditioning with vagus nerve electrical stimulation (POES) group and limb remote ischemia postconditioning (LRIPOC) group.In the groups other than the sham group,the myocardial ischemia reperfusion model was preparated by ligation of left ...

العلاقة: 国际麻醉学与复苏杂志.2014,35,(2),110-115.; 1156254; http://hdl.handle.net/20.500.11897/271149Test

الإتاحة: https://doi.org/20.500.11897/271149Test
https://doi.org/10.3760/cma.j.issn.1673-4378.2014.02.04Test
https://hdl.handle.net/20.500.11897/271149Test

المؤلفون: 王宁, 王贵松, 于海奕, 米琳, 郭丽君, 高炜

المساهمون: 北京大学第三医院心内科,卫生部心血管分子生物学与调节肽重点实验室,分子心血管学教育部重点实验室,北京100191, 北京大学国际医院心内科,北京102206

المصدر: 万方 ; 知网 ; http://d.g.wanfangdata.com.cn/Periodical_bjykdxxx201406004.aspxTest

مصطلحات موضوعية: 缺血后适应 心肌梗死 经皮冠状动脉介入治疗 心肌再灌注损伤 Ischemic postconditioning Myocardial infarction Percutaneous coronary intervention Myocardial reperfusion injury

الوصف: 目的:评价肢体远隔缺血后适应在急性ST段抬高型心肌梗死(ST-segment elevation myocardial infarction,STEMI)患者行直接经皮冠状动脉介入治疗(percutaneous coronary intervention,PCI)术中的心肌保护作用.方法:选择2014年1月至4月在北京大学第三医院心内科接受直接PCI治疗的急性STEMI患者46例,随机分为远隔缺血后适应组(n=23)和常规PCI组即对照组(n=23).远隔缺血后适应组在PCI术前于左下肢绑缚无创血压袖带,术中第一次球囊扩张或血栓抽吸而恢复血流后1 min内开始充气加压阻断左下肢血流,充气5 min,放气5 min,交替3个循环.比较两组酶学心肌梗死面积、术后1 hST段完全回落率、梗死相关动脉(infarct-related artery,IRA)、校正TIMI(thrombolysis in myocardial infarction)帧数(corrected TIMI frame count,CTFC)的差异以及直接PCI术前、术后血浆丙二醛(malondialdehyde,MDA)、内皮素-1(endothelin-1,ET-1)、肿瘤坏死因子α(tumor necrosis factor α,TNFα)水平的变化.结果:两组酶学心肌梗死面积比较差异无统计学意义(P＞0.05);远隔缺血后适应组PCI术后1 hST段完全回落率高于对照组(60.9％ vs.30.4％,P=0.04);PCI术后CTFC在远隔缺血后适应组有降低趋势(28 ±11 vs.33±11,P=0.10),在前壁STEMI患者远隔缺血后适应组显著低于对照组(25±9vs.39±10,P=0.01).远隔缺血后适应组血浆MDA、ET-1、TNFα水平于直接PCI术后不同时间点显著低于对照组(P＜0.05).结论:肢体远隔缺血后适应可改善急性STEMI患者直接PCI术后心肌组织灌注水平,减轻缺血再灌注损伤,其机制可能与减轻氧化应激、保护内皮功能、抑制炎症反应等因素有关. ; 国家自然科学基金; the National Natural Science Foundation of China ; 中文核心期刊要目总览(PKU) ; 中国科技核心期刊(ISTIC) ; 中国科学引文数据库(CSCD) ; 0 ; 6 ; 838-843 ; 46

العلاقة: 北京大学学报（医学版）.2014,46,(6),838-843.; 833644; http://hdl.handle.net/20.500.11897/225473Test

الإتاحة: https://doi.org/20.500.11897/225473Test
https://doi.org/10.3969/j.issn.1671-167X.2014.06.004Test
https://hdl.handle.net/20.500.11897/225473Test

المؤلفون: 王强, 李瑞萍, 薛富善, 程怡, 崔昕龙, 王世玉, 廖旭, 刘建华

المساهمون: 100044,北京大学人民医院麻醉科, 中国医学科学院 北京协和医学院整形外科医院麻醉科

المصدر: 万方 ; http://d.g.wanfangdata.com.cn/Periodical_zhmzxzz98201308024.aspxTest

مصطلحات موضوعية: 心肌再灌注损伤 1-磷脂酰肌醇3-激酶 蛋白质丝氨酸苏氨酸激酶 蛋白激酶B STAT转录因子类 迷走神经 电刺激 后肢 缺血后处理 Myocardial reperfusion injury 1-Phosphatidylinositol 3-kinase Protein-serine-threonine kinases STAT franscription factors Vagus nerve Electrical stimulation Hind limb Ischemic postconditioning

الوصف: 目的 探讨磷酸肌醇3激酶(PI3K)/蛋白激酶B(Akt)和Janus蛋白酪氨酸激酶(JAK)/信号转导与转录激活因子(STAT)信号转导通路在迷走神经电刺激后处理、肢体远隔缺血后处理以及迷走神经电刺激后处理联合肢体远隔缺血后处理减轻大鼠心肌缺血再灌注损伤中的作用.方法 雄性SD大鼠20只,8周龄,体重290 ～ 320 g,采用随机数字表法,将其分为4组(n=5):缺血再灌注组(1/R组)、迷走神经电刺激后处理组(EVSP组)、肢体远隔缺血后处理组(RLIP组)、迷走神经电刺激后处理联合肢体远隔缺血后处理组(EVSP-RLIP组).采用结扎冠状动脉左前降支30 min再灌注60 min的方法制备心肌缺血再灌注模型.EVSP组和EVSP-RLIP组在心肌缺血15 min时对右侧迷走神经干实施电刺激30 min,参数设置:波宽1 ms,频率10 Hz、刺激电流随大鼠HR进行调整,以保持HR较刺激前降低10％.RLIP组和EVSP-RLIP组在心肌缺血20 min时采用止血带结扎双后肢10 min后恢复血流灌注行肢体远隔缺血后处理.缺血再灌注期间记录血流动力学指标.再灌注60 min时采集颈静脉血样,采用酶联免疫吸附法检测血清肌钙蛋白I(cTnI)和MB型肌酸激酶同工酶(CK-MB)的浓度；处死动物,取缺血区和非缺血区心肌组织,采用Western blot法检测磷酸化Akt(p-Akt)和磷酸化STAT3(p-STAT3)蛋白的水平；采用RQ-PCR法检测Akt和STAT3 mRNA的表达水平.结果 与IR组比较,POES组、LRIP组和POES-LRIP组缺血再灌注期间HR降低,血清cTnI和CK-MB浓度降低,缺血区和非缺血区心肌p-Akt和p-STAT3蛋白表达上调,EVSP-LRIP组缺血区和非缺血区心肌Akt和STAT3的mRNA表达上调(P＜0.05).与EVSP组和LRIP组比较,EV SP-LRIP组血清CK-MB浓度降低,缺血区和非缺血区心肌p-Akt、p-STAT3蛋白表达及Akt和STAT3的mRNA表达上调(P＜0.05).结论 PI3K/Akt和JAK/STAT信号转导通路激活后介导了迷走神经电刺激后处理、肢体远隔缺血后处理和两者联合应用时减轻大鼠心肌缺血再灌注损伤的作用. ; 国家自然科学基金面上资助项目; 北京协和医学院协和青年科研基金 ; 中文核心期刊要目总览(PKU) ; 中国科技核心期刊(ISTIC) ; 中国科学引文数据库(CSCD) ; 0 ; 8 ; 997-1002 ; 33

العلاقة: 中华麻醉学杂志.2013,33,(8),997-1002.; 1207152; http://hdl.handle.net/20.500.11897/282851Test

الإتاحة: https://doi.org/20.500.11897/282851Test
https://doi.org/10.3760/cma.j.issn.0254-1416.2013.08.024Test
https://hdl.handle.net/20.500.11897/282851Test

المؤلفون: 王强, 李杉, 薛富善, 袁玉静, 熊军, 程怡, 李瑞萍, 廖旭, 刘建华

المساهمون: 北京大学人民医院麻醉科,100044, 中国医学科学院北京协和医学院整形外科医院麻醉科

المصدر: 万方 ; http://d.g.wanfangdata.com.cn/Periodical_gwyx-mzxyfsfc201303008.aspxTest

مصطلحات موضوعية: 心肌缺血/再灌注损伤, 炎症反应, 缺血预处理, 肢体远隔缺血后处理, Myocardial ischemia/reperfusion injury, Inflammatory response, Ischemic preconditioning, Limb remote ischemic postconditioning

الوصف: 目的 比较缺血预处理(ischemic preconditioning,IPC)和肢体远隔缺血后处理(limb remote ischemic postconditioning,LRIPOC)对大鼠心肌缺血/再灌注损伤(ischemia/reperfusion injury,I/RI)中炎症反应的影响. 方法 雄性SD大鼠80只,体重250 g～350 g,采用随机数字表法将其随机分为4组(每组20只):假手术组(S组)、缺血/再灌注组(I/R组)、IPC组和LRIPOC组.监测缺血/再灌注期间的心率(HR)和平均动脉压(MAP),并计算HR和收缩压乘积(rate pressure product,RPP)作为心肌氧耗指数.各组随机取10只大鼠,于再灌注30、60、120 min时采集颈静脉血样,采用ELISA法检测血清心肌肌钙蛋白(cardiac troponin I,cTnI)、磷酸肌酸激酶同工酶(creatine kinase-MB,CK-MB)、肿瘤坏死因子(tumor necrosis factor,TNF)-α、高迁移率组蛋白-1(high mobility group box-1 protein,HMGB-1)、细胞间黏附分子-1(intercellular adhesion molecule-1,ICAM-1)、白介素(interleukin,IL)-1、IL-6和IL-10的浓度；于再灌注120 min颈静脉采血后,采用伊文蓝和TTC双重染色法测定心肌梗死体积.各组随机取10只大鼠,于再灌注120 min处死后分别取缺血区和非缺血区心肌组织,采用ELISA法检测心肌TNF-α 、HMGB-1、ICAM-1、IL-1、IL-6和IL-10含量. 结果 I/R组、IPC组和LRIPOC组的心肌梗死体积值分别是(72±9)％、(36±13)％和(57±9)％,3组的血清cTnI浓度分别是(0.99±0.14)(0.37±0.08)、(0.54±0.07) μg/L,而3组的血清CK-MB浓度分别是(110±13)、(38±8)、(45±6) μg/L.与I/R组比较,IPC组和LRIPOC组心肌梗死体积、血清cTnI和CK-MB浓度显著降低,IPC组再灌注30、60、120 min时血清TNF-α 浓度、再灌注60、120 min时血清HMGB-1浓度、再灌注120 min时血清ICAM-1、IL-1和IL-6浓度显著降低,缺血区心肌组织内TNF-α 、HMGB-1、ICAM-1、IL-1和IL-6含量显著降低,非缺血区心肌组织内TNF电、ICAM-1、IL-1和IL-6含量显著降低(P＜0.05)；LRIPOC组再灌注30、60、120 min时血清TNF-α 浓度、再灌注120 min时血清HMGB-1、ICAM-1、IL-1和IL-6浓度显著降低,缺血区与非缺血区心肌组织内 TNF-α、HMGB-1、ICAM-1、IL-1和IL-6的含量显著降低(P＜0.05).与IPC组比较,LRIPOC组的心肌梗死体积、血清cTnI和CK-MB浓度显著升高,再灌注60 min时血清TNF-α 浓度、再灌注120 min时血清HMGB-1和ICAM-1浓度显著升高,缺血区心肌组织内TNF-α 、ICAM-1、IL-1和IL-6含量显著升高,非缺血区心肌组织内ICAM-1、IL-1和IL-6含量显著升高(P＜0.05). 结论 IPC减轻大鼠心肌I/RI中炎症反应的作用强于LRIPOC,这可能是IPC对心肌I/RI保护作用强于LRIPOC的原因之一. ; Objective To compare the effects of ischemic preconditioning with limb remote ischemic postconditioning on inflammatory response during myocardial ischemia/reperfusion injury (I/RI) in rat in vivo.Methods Eighty male Sprague-Dawley rats weighing 250 g-350 g were randomly allocated into four groups (n=20 in each group):sham group (S group); ischemia reperfusion group (I/R group); ischemic preconditioning group (IPC group) and limb remote ischemic postconditioning group (LRIPOC group).In the groups other than the sham group,the ...

العلاقة: 国际麻醉学与复苏杂志.2013,34,(3),224-229.; 1263701; http://hdl.handle.net/20.500.11897/135895Test

الإتاحة: https://doi.org/20.500.11897/135895Test
https://doi.org/10.3760/cma.j.issn.1673-4378.2013.03.008Test
https://hdl.handle.net/20.500.11897/135895Test