Protective effect of necrostatin-1 on myocardial tissue in rats with acute myocardial infarction
Protective effect of necrostatin-1 on myocardial tissue in rats with acute myocardial infarction
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DOI：
10.4238/gmr.15027298
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发表时间：
2016-01-01
影响因子：
0.4
通讯作者：
Xu, H. M.
中科院分区：
文献类型：
--
作者：
Liu, Y. R.;Xu, H. M.
本研究旨在探讨necrostatin-1对急性心肌梗死（AMI）大鼠心肌组织的保护作用，为necrostatin-1治疗急性心肌梗死提供依据。通过结扎左冠状动脉前降支建立AMI大鼠（45只）。将大鼠随机分为模型组和necrostatin-1低剂量组和高剂量组。对照组大鼠（15只）进行假手术。 necrostatin-1低剂量组和高剂量组大鼠分别经尾静脉注射1 mg/kg necrostatin-1和4 mg/kg。对照组和模型组大鼠注射等量二甲亚砜，每日1次，连续3天。采用实时聚合酶链反应和蛋白质印迹法检测大鼠心肌组织中RIP1和RIP3 mRNA及磷酸化蛋白的水平。采用氯化四唑检测心肌梗死面积。与对照组相比，模型组、necrostatin-1低剂量组、高剂量组大鼠心肌组织中RIP1、RIP3 mRNA及磷酸化蛋白水平均显着升高。 necrostatin-1低剂量组和高剂量组大鼠心肌组织中RIP1、RIP3 mRNA及磷酸化蛋白水平均较模型组显着降低（P < 0.05）。高剂量组大鼠心肌中RIP1、RIP3 mRNA水平显着低于低剂量组（P < 0.05）。模型组、低剂量组和高剂量组大鼠心肌梗塞面积显着增加。 necrostatin-1治疗后低剂量组和高剂量组心肌细胞凋亡水平明显降低，但仍高于对照组（P < 0.05）。综上所述, necrostatin-1能够抑制急性心肌梗死大鼠心肌组织凋亡和坏死, 对心肌组织具有保护作用。
The aim of this study was to investigate the protective effect of necrostatin-1 on myocardial tissue of acute myocardial infarction (AMI) rats and to provide a basis for necrostatin-1 for the treatment of acute myocardial infarction. AMI rats (45) were established by ligating the anterior descending branch of the left coronary artery. The rats were randomly divided into the model group and necrostatin-1 low-dose and high-dose groups. The control group rats (15) underwent the sham operation. The rats in the necrostatin-1 low-dose and high-dose groups were injected with 1 and 4 mg/kg necrostatin-1, respectively, via the tail vein. The rats in the control and model groups were injected with isometric dimethyl sulfoxide, once daily, for 3 consecutive days. The levels of RIP1 and RIP3 mRNA and phosphorylated protein in the myocardial tissue of rats were detected by real time polymerase chain reaction and western blot. The myocardial infarct size was detected by tetrazolium chloride. Compared with that in the control group, the levels of RIP1 and RIP3 mRNA and phosphorylated protein significantly increased in the myocardial tissue of model group rats, necrostatin-1 low-dose group, and high-dose group. The levels of RIP1 and RIP3 mRNA and phosphorylated protein in the myocardial tissue of rats in the necrostatin-1 low-dose and high-dose groups decreased significantly compared with that in the model group (P < 0.05). The levels of RIP1 and RIP3 mRNA in the myocardium of the high-dose group rats were significantly lower than those of the low-dose group rats (P < 0.05). The myocardial infarct sizes significantly increased in model, low-dose, and high-dose group rats. The apoptotic level of myocardial cells significantly decreased in the low-dose group and high-dose group after treatment with necrostatin-1 but was still higher than that of the control group (P < 0.05). In conclusion, necrostatin-1 can inhibit myocardial tissue apoptosis and necrosis in acute myocardial infarct rats and has a protective effect on myocardial tissue.