蛋白酶体抑制剂MG-132对心肌梗死后心衰大鼠心功能及心肌肌钙蛋白Ⅰ的影响

来源 :第三军医大学学报 | 被引量 : 0次 | 上传用户:wuhaozzu
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目的探讨泛素蛋白酶体系统对心肌梗死后心衰大鼠心功能及心肌肌钙蛋白Ⅰ的影响。方法将制作成功的心肌梗死后心衰大鼠模型纳入研究,45只大鼠随机分为:①MG-132组:结扎左冠状动脉前降支,腹腔内注射MG-1320.1 mg/(kg.d)(溶于2 ml生理盐水);②心肌梗死(MI)组:结扎左冠状动脉前降支,腹腔内注射2 ml/d生理盐水;③假手术(Sham)组:手术过程同心肌梗死组,但只穿线通过左冠状动脉前降支不打结,腹腔内注射2 ml/d生理盐水。所有腹腔内注射持续7周后,检测各组大鼠心脏血流动力学及血清脑钠肽水平,电镜检测心肌肌小节结构变化,Real-time PCR及Western blot方法检测心肌cTnI的mRNA水平和蛋白质表达。结果与MI组相比,MG-132组大鼠心衰所致死亡率有降低趋势(0vs20%),LVPS及+dp/dtmax升高(分别为[85.69±14.65)vs(71.22±7.89)mmHg,P<0.05;(2 327.57±597.96)vs(1 047.20±168.65)mmHg/s,P<0.01],LVEDP下降[(16.85±2.05)vs(23.40±6.08)mmHg,P<0.01],NT-proBNP水平降低[(1 474.15±702.61)vs(3 920.56±1 919.04)pg/ml,P<0.001];MG-132还改善了肌小节结构,上调cTnI的mRNA及蛋白质表达[分别为(2.4±1.1)vs(0.6±0.2),P<0.01;(0.83±0.07)vs(0.63±0.10),P<0.05]。结论 MG-132改善了肌小节结构,与上调cTnI的mRNA及蛋白质表达有关。 Objective To investigate the effect of ubiquitin proteasome system on cardiac function and cardiac troponin Ⅰ in rats with heart failure after myocardial infarction. Methods The successful rat models of heart failure after myocardial infarction were included in the study. 45 rats were randomly divided into: ① MG-132 group: MG-1320.1 mg / (kg · d) (Dissolved in 2 ml of normal saline); ② myocardial infarction (MI) group: ligation of left anterior descending coronary artery, intraperitoneal injection of 2 ml / d saline; ③ sham group: But only through the left anterior descending coronary artery do not tie knot, intraperitoneal injection of 2 ml / d saline. All rabbits were intraperitoneally injected for 7 weeks. The hemodynamics and serum brain natriuretic peptide of the rats in each group were measured. The changes of myocardial muscle structure were detected by electron microscopy. The mRNA and protein levels of cTnI in myocardium were detected by Real-time PCR and Western blot. expression. Results Compared with MI group, the death rate of heart failure in MG-132 group was decreased (0 vs. 20%) and LVPS and + dp / dtmax were increased (85.69 ± 14.65 vs 71.22 ± 7.89 mmHg (P <0.01), P <0.05; (2 327.57 ± 597.96) vs (1047.20 ± 168.65) mmHg / s, P <0.01] MG-132 also improved the structure of the myotubes and up-regulated the mRNA and protein expression of cTnI [(2.4 ± 0.06 ± 0.06, P <0.001) 1.1) vs (0.6 ± 0.2), P <0.01; (0.83 ± 0.07) vs (0.63 ± 0.10), P <0.05]. Conclusion MG-132 can improve the structure of myotubes, which is related to the up-regulation of cTnI mRNA and protein expression.
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