【摘要】 目的探讨线粒体分裂抑制剂(Mdivi-1)在海马神经元缺氧复氧损伤中的保护作用及机制。方法将体外培养的大鼠海马神经元采用随机数字表法分为正常细胞组(N组)、赋形剂组(V组)、缺血/再灌注组(I/R组)、Mdivi-1组(M组),利用氧糖剥夺法建立海马神经元缺氧复氧模型,缺氧6 h后复氧20 h,测定海马神经元线粒体内钙离子浓度、线粒体分裂相关蛋白(Drp1、Bcl-2、Bax、Cyt C)的表达含量及细胞凋亡率。结果 4组海马神经元线粒体内钙离子浓度比较,差异有统计学意义(P<0.05)。N组、V组海马神经元线粒体内钙离子浓度比较,差异无统计学意义(P>0.05);I/R组海马神经元线粒体内钙离子浓度高于N组、V组(P<0.05)。M组海马神经元线粒体内钙离子浓度低于I/R组(P<0.05)。4组Drp1、Bcl-2、Bax、Cyt C表达量比较,差异有统计学意义(P<0.05)。N组、V组Drp1、Bcl-2、Bax、Cyt C表达量比较,差异无统计学意义(P>0.05)。I/R组Drp1、Bax、Cyt C表达量高于N组、V组,Bcl-2表达量低于N组、V组(P<0.05)。M组Drp1、Bax、Cyt C表达量低于I/R组,Bcl-2表达量高于I/R组(P<0.05)。4组细胞凋亡率比较,差异有统计学意义(P<0.05)。N组、V组细胞凋亡率比较,差异无统计学意义(P>0.05);I/R组细胞凋亡率高于N组、V组(P<0.05)。M组细胞凋亡率低于I/R组(P<0.05)。结论Mdivi-1可降低海马神经元线粒体内钙离子浓度,调控Drp1、Bax、Cyt C、Bcl-2表达,抑制线粒体分裂,降低细胞凋亡,从而起到脑保护作用。更多还原

【Abstract】 Objective To investigate protective effect and mechanism of mitochondrial mitosis inhibitors on hypoxiareoxygenation injury of hippocampal neurons.Methods Rat hippocampal neurons cultured in vitro were randomly divided into normal cell group(N group),excipient group(V group),ischemia/reperfusion group(I/R group) and Mdivi-1 group(M group).The hypoxia-reoxygenation model of hippocampal neurons was established by oxygen-glucose deprivation method.The concentration of calcium ion in mitochondria of hippocampal neurons was measured after 6 hours of hypoxia and 20 hours of reoxygenation.The expression of mitochondrial division-related proteins(Drp1,Bcl-2,Bax,Cyt C) and the apoptotic rate were measured.Results There was significant difference in calcium concentration in mitochondria of hippocampal neurons among the four groups(P<0.05).There was no significant difference in the concentration of calcium in mitochondria of hippocampal neurons between N group and V group(P>0.05);the concentration of calcium in mitochondria of hippocampal neurons in group I/R was higher than N group and V group(P<0.05).The concentration of calcium in mitochondria of hippocampal neurons in M group was lower than I/R group(P<0.05).The expression levels of Drp1,Bcl-2,Bax and Cyt C among the four groups were significantly different(P<0.05).There was no significant differences in the expression levels of Drp1,Bcl-2,Bax and Cyt C between N group and V group(P>0.05).The expression levels of Drp1,Bax and Cyt C in I/R group were higher than N group and V group,and the expression levels of Bcl-2 were lower than N group and V group(P<0.05).The expression levels of Drp1,Bax and Cyt C in M group were lower than I/R group,and the expression levels of Bcl-2 were higher than I/R group(P<0.05).There was significant difference in apoptotic rate between the four groups(P<0.05).There was no significant difference in the apoptotic rate between N group and V group(P>0.05);the apoptotic rate of I/R group was higher than N group and V group(P<0.05).The apoptotic rate of M group was lower than I/R group(P<0.05).Conclusion Mdivi-1 can decrease the concentration of calcium ion in mitochondria of hippocampal neurons,regulate the expression of Drp1,Bax,Cyt C and Bcl-2,inhibit mitochondrial division and reduce apoptosis,thus playing a protective role in brain.更多还原