环孢素A对高糖状态下七氟醚后处理大鼠心肌细胞保护作用的影响  

Cyclosporin A on Cardioprotective Effect of Sevoflurane Postconditioning under High Glucose Concentration in Rat

作　　者：俞瑾[1] 詹海婷[1] 程虎[1] 李玉倩 郑宏[1] YU Jin;ZHAN Hai-ting;CHENG Hu;LI Yu-qian;ZHENG Hong(Department of Anesthesiology the First Affiliated Hospital of Xinjiang Medical University,Urumqi 830054,China)

机构地区：[1]新疆医科大学第一附属医院麻醉科,乌鲁木齐830054

出　　处：《实验动物与比较医学》2018年第5期329-335,共7页Laboratory Animal and Comparative Medicine

基　　金：国家自然科学基金地区科学基金项目(31760327)

摘　　要：目的明确环孢素A(CsA)能否通过抑制线粒体通透性转换孔(mPTP)开放,并维持线粒体形态恢复七氟醚后处理(SPostC)对高糖培养心肌细胞的保护作用。方法原代培养SD乳鼠心肌细胞,分别在低糖与高糖浓度下培养48 h后接受缺氧复氧损伤。缺氧前给予CsA或者再灌注前给予SPostC,或二者联合应用,观察心肌细胞复氧后的死亡率、乳酸脱氢酶(LDH)水平、线粒体形态改变及线粒体膜电位变化。结果 SPostC与CsA均降低了缺氧/复氧损伤后的LDH水平与细胞死亡率,增加了缺氧/复氧损伤后的线粒体平均面积/周长比与线粒体膜电位水平(P<0.05),二者联合并未进一步增强保护作用。高糖(35 mmol/L)加剧了心肌细胞缺氧/复氧损伤,高糖浓度下,上述保护作用均消失。与高糖组相比,SPostC、CsA及二者联合均未能降低缺氧/复氧损伤后的LDH水平与细胞死亡率(P>0.05),线粒体平均面积/周长比与线粒体膜电位水平变化差异也无统计学意义。结论 CsA和SPostC均能够通过调节线粒体形态抵抗缺氧/复氧损伤,高糖时保护作用消失,联合CsA无法恢复其保护效应。Objective To evaluate whether cyclosporin A（CsA） restore the cardioprotective effect of sevoflurane postconditioning （SPostC） against hypoxia/reoxygenation（H/R） injury in rat under high concentration of glucose through inhibiting mitochondrial permeability transition pore opening and main taining mitochondrial morphology. Methods Primary cultures of neonatal rat cardiomyocytes in low and high concentrations of glucose for 48 h were subjected to HR（3 hr hypoxia followed by 3 hr reoxygenation）, treated with SPostC before perfusion or CsA before gypoxia, or combined use of these two interventions were performed before hypoxia. Cell death, lactate dehydrogenase （LDH） level, mitochondrial morphology and mitochondrial membrane potential were measured after H/R injury.Results Both SPostC and CsA decreased cell death, LDH level, increased mitochondrial interconnectivity and mitochondrial membrane potential following H/R（P〈0.05）, combination of these two interventions did not further enhance the protective effects. High concentration of glucose（35 mmol/L） eliminated the cardioprotective effect mentioned above. As compared with high glucose group, SPostC or CsA,or combined use of these two interventions did not affect the cell death, LDH level, mitochondrial interconnectivity and mitochondrial membrane potential following H/R（P〈0.05）. Conclusion Both SPostC and CsA can protect cardiomyocytes against H/R injury through maintaining mitochondrial morphology. High concentration of glucose eliminates the cardioprotective effect, and CsA can not restore the cardioprotective effect of SPostC under high concentration of glucose.

关 键 词：环孢素A(CsA) 七氟醚后处理(SPostC) 高糖 原代心肌细胞 缺氧/复氧损伤 

分 类 号：Q95-33[生物学—动物学]