摘要
目的探讨丙泊酚后处理(propofol postconditioning,P-Post C)在高糖环境下对H9c2心肌细胞缺血/复氧诱导的凋亡和自噬的改善作用。方法2023年4月于上海市奉贤区中心医院开展实验,将大鼠心脏来源的H9c2细胞暴露于高糖48 h,然后在不存在或存在不同浓度的P-Post C后处理的情况下,在缺氧/复氧(hypoxia/reoxygenation,H/R)。细胞分组:NC组、HG组、NC+H/R组、HG+H/R组、HG+H/R+P12.5组、HG+H/R+P25组、HG+H/R+P50组、HG+H/R+P100组和HG+H/R+P25+Brusatol组。确定丙泊酚的浓度后,在使用或不使用Nrf2/HO-1通路抑制剂的情况下,对H9c2细胞进行H/R和P-Post C处理,以探索它们在P-Post C介导的高糖下对凋亡和自噬细胞死亡的保护中的作用。结果结果显示,含或不含H/R的高糖降低了H9c2细胞的活力,增加了乳酸脱氢酶的释放和活性氧的产生,所有这些都被P-Post C显著逆转,尤其是在25μmol/L(P25)浓度下(P<0.05)。此外,发现丙泊酚(P25)降低H9c2细胞的凋亡和自噬,同时增加Nrf2和HO-1的表达(P<0.05)。丙泊酚(P25)对H/R损伤的保护作用通过使用Nrf2/HO-1通路抑制剂而逆转(P<0.05)。结论P-Post C通过上调高糖状态下的Nrf2/HO-1通路活性,减轻了H/R损伤诱导的H9c2心脏细胞凋亡和自噬。
Objective To investigate the effect of propofol postconditioning(P-PostC)on apoptosis and autophagy induced by ischemia/reoxygenation in H9c2 cardiomyocytes under high glucose environment.Method In Fengxian District Central Hospital of Shanghai in April 2023,Rat heart-derived H9c2 cells were exposed to high glucose for 48 h,and then subjected to hypoxia/reoxygenation(H/R)in the absence or presence of different concentrations of P-PostC postconditioning.The cells were divided into groups as:NC group,HG group,NC+H/R group,HG+H/R group,HG+H/R+P12.5 group,HG+H/R+P25 group,HG+H/R+P50 group,HG+H/R+P100 group and HG+H/R+P25+Brusatol group.After the concentration of propofol was determined,H/R and P-PostC treatments were performed on H9c2 cells with or without Nrf2/HO-1 pathway inhibitors to explore their role in the protection of apoptosis and autophagic cell death under P-PostC-mediated high glucose.Results The results showed that high glucose with or without H/R decreased the viability of H9c2 cells,increased the release of lactate dehydrogenase and the production of reactive oxygen species,all of which were significantly reversed by P-PostC,especially at 25μmol/L(P25)concentration(P<0.05).In addition,it was found that propofol(P25)reduced the apoptosis and autophagy of H9c2 cells and increased the expression of Nrf2 and HO-1(P<0.05)meanwhile.The protective effect of propofol(P25)on H/R injury was reversed by using Nrf2/HO-1 pathway inhibitors(P<0.05).Conclusion P-PostC would reduce H/R-induced apoptosis and autophagy in H9c2 heart cells by up-regulating the activity of Nrf2/HO-1 pathway in the high glucose state.
作者
曹炜炜
张欢
张月梅
刘建军
CAO Wei-wei;ZHANG Huan;ZHANG Yue-mei;LIU Jian-jun(Department of Anesthesiology,Fengxian Central Hospital,Shanghai 201299,China;Department of Emergency,Fengxian Central Hospital,Shanghai 201299,China)
出处
《中国心血管病研究》
CAS
2024年第2期185-192,共8页
Chinese Journal of Cardiovascular Research
基金
上海市卫生系统优秀青年医学人才培养项目(PWRq2021-1012)。
