摘要
目的探讨线粒体缝隙连接蛋白43(Cx43)和活性氧及蛋白激酶Cε(PKCε)信号通路在缺血后处理中的心脏保护作用。方法将40只雄性SD大鼠建立心脏缺血再灌注(IR)损伤模型,随机分为假手术组(Sham组)、IR组、IPC组和IPC+N-乙酰半胱氨酸(NAC)组(腹腔注射NAC 150mg/kg,15min后IPC处理),每组10只。应用伊文思蓝/TTC双染色检测心肌梗死面积,检测乳酸脱氢酶(LDH)及肌酸激酶同工酶(CK-MB)活性,TUNEL检测心肌细胞凋亡,荧光探针测定心肌线粒体活性氧水平,Western blot检测心肌线粒体总Cx43、磷酸化Cx43和PKCε蛋白表达。结果与IR组比较,IPC组心肌梗死面积显著降低[(27.97±4.26)%vs (46.78±3.32)%],心肌酶LDH及CK-MB、心肌细胞凋亡率及线粒体活性氧生成下降;上调线粒体总Cx43、磷酸化Cx43和PKCε蛋白表达。IPC+NAC组大鼠心肌梗死面积、LDH及CK-MB、心肌细胞凋亡较IPC组显著升高(P<0.05),心肌线粒体PKCε蛋白表达较IPC组显著下调(P<0.05)。结论活性氧信号介导IPC心脏保护,该保护作用与线粒体Cx43及PKCε密切相关,Cx43和活性氧及PKCε信号通路在IPC的心脏保护中发挥重要作用。
Objective To study the role of mitochondrial Cx43/ROS/PKC signaling pathway and IPC in protecting heart against IR injury.Methods A rat cardiac IR injury model was established and IPC and NAC (150mg/kg)were administered.Fourty male SD rats were divided into sham operation group,IR injury group,IPC group,and IPC+NAC group (10in each group).The size of myocardial infarction (MCI)was measured with Evans bhe/TTC staining.The activity of LDH and CK-MB was assayed using a biochemical analyzer.The apoptosis of cardiomyocytes was detec- ted with TUNEL staining.Results The size of MCI was significantly smaller,the activity of LDH,CK-MB and m{tochondrial ROS and the apoptosis rate of cardiomyocytes were significantly lower while the protein levels of mitochondrial total and phosph Cx43and PKCε were significant- ly higher in IPC group than in IR injury group.The size of MCI was significantly larger,the activ- ity of LDH,CK-MB and mitochondrial ROS and the apoptosis rate of cardiomyocytes were signifi- cantly higher while the protein level of mitochondrial PKCε was significantly lower in IPC+NAC group than in IPC group (P<0.05).Conclusion The Cx43/ROS/PKCε signaling pathway plays an important role in IPC protecting heart against IR injury.
作者
涂荣会
钟国强
曾志羽
文宏
黄政
黎庆捷
张馨月
蒙健军
Tu Ronghui;Zhong Guoqiang;Zeng Zhiyu;Wen Hong;Huang Zheng;Li Qingjie;Zhang Xinyue;Meng Jianjun(Department of Geriatric Cardiology,First A filiated Hospital of Guangxi Medical University,Nanning 530000,Guangxi Zhuang Autonomous Region,China)
出处
《中华老年心脑血管病杂志》
CAS
北大核心
2018年第12期1302-1306,共5页
Chinese Journal of Geriatric Heart,Brain and Vessel Diseases
基金
国家自然科学基金(81560068)
广西自然科学基金(2015GXNSFAA139198)
关键词
线粒体
连接蛋白类
活性氧
蛋白激酶C
mitochondria
connexins
reactive oxygen species
protein kinase C