Propofol post‐conditioning alleviates hepatic ischaemia reperfusion injury via BRG1‐mediated Nrf2/HO‐1 transcriptional activation in human and mice
| العنوان: | Propofol post‐conditioning alleviates hepatic ischaemia reperfusion injury via BRG1‐mediated Nrf2/HO‐1 transcriptional activation in human and mice |
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| المؤلفون: | Qianqian Zhu, Yi Jin, Weifeng Yao, Dongdong Yuan, Mian Ge, Huixin Chen, Ziqing Hei, Chaojin Chen, Jun Cai |
| المصدر: | Journal of Cellular and Molecular Medicine |
| بيانات النشر: | John Wiley and Sons Inc., 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, Male, medicine.medical_treatment, Cell, Pharmacology, Liver transplantation, medicine.disease_cause, Antioxidants, post‐conditioning, Hepatitis, chemistry.chemical_compound, Mice, Hypnotics and Sedatives, Prospective Studies, Propofol, chemistry.chemical_classification, reactive oxygen species, medicine.diagnostic_test, liver transplantation, Liver Neoplasms, Nuclear Proteins, respiratory system, Middle Aged, medicine.anatomical_structure, Liver, Reperfusion Injury, Molecular Medicine, Original Article, Female, medicine.drug, Adult, Adolescent, NF-E2-Related Factor 2, Cell Line, 03 medical and health sciences, Lactate dehydrogenase, medicine, Animals, Humans, Aged, Reactive oxygen species, DNA Helicases, Drug Repositioning, Cell Biology, Original Articles, medicine.disease, nuclear‐related factor 2, Mice, Inbred C57BL, Oxidative Stress, 030104 developmental biology, chemistry, Gene Expression Regulation, ischaemia reperfusion injury, Hepatocytes, Liver function tests, Reperfusion injury, Oxidative stress, Brahma‐related gene 1, Heme Oxygenase-1, Transcription Factors |
| الوصف: | To explore the effects of propofol post‐conditioning (PPC) on hepatic ischaemia/reperfusion injury (HIRI) and the potential mechanisms that might be involved in the interaction of Brahma‐related gene1(BRG1) and Nuclear‐related factor 2(Nrf2). Patients were randomized into PPC(n = 16) and non‐PPC(NPC)( n = 21) groups. Propofol(2 mg/kg) was infused within 10 min. of the onset of liver reperfusion during liver transplantation in the PPC group. Liver function tests, as well as Brg1, Nrf2, Heme oxygenase‐1(HO‐1) and NADPH:quinone oxidoreductase1(NQO1) expression levels were evaluated. CMV‐Brg1 mice were designed to investigate the role of Brg1 overexpression during HIRI. Brg1 and Nrf2 siRNA were used to examine the relationship between Brg1 and Nrf2/HO‐1 pathways in propofol‐mediated effects in a human hepatocyte(L02) hypoxia/reoxygenation(H/R) model. In patients, PPC attenuated both donor liver pathological and function injury, and reducing oxidative stress markers, compared to the NPC group, 24 hrs after surgery. PPC increased liver Brg1, Nrf2, HO‐1 and NQO1 expression. In mice, PPC reduced HIRI by decreasing liver oxidative stress and activating Nrf2/HO‐1 pathway, accompanied by up‐regulation of BRG1 expression. BRG1 overexpression activated Nrf2/HO‐1 transcription in CMV‐BRG1 mice during HIRI. In vitro, PPC significantly elevated expression of Nrf2, HO‐1 and NQO1, resulting in a reduction of cell DCFH‐DA and 8‐isoprostane levels and decreased lactate dehydrogenase levels, leading to an overall increase in cell viability. Moreover, the protective effects of propofol were partially abrogated in Nrf2‐knock‐down or BRG1‐knock‐down hepatocytes. Nrf2‐knock‐down drastically reduced protein expression of HO‐1 and NQO1, while Brg1‐knock‐down decreased HO‐1 expression. Propofol post‐conditioning alleviates HIRI through BRG1‐mediated Nrf2/HO‐1 transcriptional activation. |
| اللغة: | English |
| تدمد: | 1582-4934 1582-1838 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::53c247a25a7bd303b77b245ff05c5ba3Test http://europepmc.org/articles/PMC5706583Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....53c247a25a7bd303b77b245ff05c5ba3 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15824934 15821838 |
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