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Title: [Role of mitochondrial permeability transition pore in mediating the effect of endomorphin-1 postconditioning against myocardial ischemia-reperfusion injury in rats].
Author: Huang YP, Yang TH, Jin ZY, Wang Y, Ye HW, Gao Q, Li ZH.
Journal: Nan Fang Yi Ke Da Xue Xue Bao; 2018 May 20; 38(5):547-553. PubMed ID: 29891450.
Abstract:
OBJECTIVE: To investigate the role of mitochondrial permeability transition pore (MPTP) opening in mediating the effect of endomorphine-1 postconditioning to alleviate myocardial ischemia-reperfusion (IR) injury in rats. METHODS: Forty-five male SD rats were randomized equally for sham operation, myocardial IR injury, endomorphin-1 postconditioning, atractyloside (a MPTP opener) postconditioning, or endomorphin-1 + atractyloside postconditioning. The hemodynamic param-eters of the rats were monitored in real time via carotid artery cannulation to the left ventricle. After reperfusion, plasma samples were collected for biochemical analyses. The size of myocardial infarct area was detected using Evans blue and TTC double staining, and the myocardial expressions of apoptosis-related proteins Bax, Bcl-2 and cleaved caspase-3 were analyzed using Western blotting. RESULTS: Myocardial IR injury resulted in significantly decreased heart rate and blood pressure in the rats (P<0.05). Compared with those in IR group, the rats with endomorphin-1 postconditioning showed significantly increased heart rate and blood pressure (P<0.05), lowered contents or activities of LDH, CK-MB, cTnI, IL-6, TNF-α, Cyt-C and MDA in the plasma (P<0.05), increased plasma SOD activity (P<0.05), reduced size of myocardial infarction, decreased myocardial expression of Bax and cleaved caspase-3 protein (P<0.05), and increased myocardial expression of Bcl-2 protein (P<0.05). All these changes induced by endomorphin-1 were obviously reversed by atractyloside postconditioning (P<0.05). CONCLUSION: Endomorphin-1 postconditioning protects against myocardial IR injury in rats probably by inhibiting the opening of MPTP and reducing cardiac myocyte apoptosis via down-regulating cleaved caspase-3 expression. 目的: 探讨线粒体通透性转换孔(MPTP)的开放对内吗啡肽-1后处理减轻心肌缺血再灌注损伤的作用。方法: 将45只雄性SD大鼠随机分为5组(n=9/组):假手术组(S组)、缺血再灌注组(IR组)、内吗啡肽-1后处理组(EM50组)、线粒体通透性转换孔开放剂苍术苷后处理组(Atr组)和内吗啡肽-1+苍术苷后处理组(EM50+Atr组)。建立大鼠在体心肌缺血再灌注模型, 通过经颈动脉插管至左心室实时监测血流动力学, 记录各组大鼠的血流动力学指标, 再灌结束后采集大鼠血浆, 检测乳酸脱氢酶、肌酸激酶、心肌肌钙蛋白I、白介素-6、肿瘤坏死因子-α, 氧化应激指标超氧化物歧化酶和丙二醛, 细胞色素C等生化指标, 大鼠心肌组织HE染色, 采用Evans blue和TTC双染色法检测心肌梗死面积, Western blot检测心肌组织中凋亡相关蛋白Bax、Bcl-2和cleaved caspase-3的表达。结果: 与S组比较, IR组心率和血压降低(P < 0.05);与IR组比较, EM50组心率和血压有所增高(P < 0.05);血浆中乳酸脱氢酶、肌酸激酶、心肌肌钙蛋白I、白介素-6、肿瘤坏死因子-α、丙二醛、细胞色素C含量或活性下降(P < 0.05), 氧化应激指标超氧化物歧化酶活性增加(P < 0.05);心肌梗死面积减少(P < 0.05); Bax和cleaved caspase-3蛋白表达量降低(P < 0.05), Bcl-2蛋白表达量升高(P < 0.05);与EM50组比较, EM50+Atr组心率和血压降低(P < 0.05);血浆中乳酸脱氢酶、肌酸激酶、心肌肌钙蛋白I、白介素-6、肿瘤坏死因子-α、丙二醛、细胞色素C含量或活性增加(P < 0.05), 超氧化物歧化酶活性降低(P < 0.05);心肌梗死面积增加(P < 0.05); Bax和cleaved caspase-3蛋白表达量升高(P < 0.05), Bcl-2蛋白表达量降低(P < 0.05)。结论: 内吗啡肽-1后处理可能通过抑制MPTP的开放, 减少线粒体中Cyt-C的释放, 下调凋亡相关蛋白cleaved caspase-3的表达, 减少心肌细胞凋亡, 减轻大鼠心肌缺血再灌注损伤, 发挥心肌保护作用。

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