瑞舒伐他汀对脓毒症大鼠心肌自噬的影响

Effect of Rosuvastatin on Myocardial Autophagy in Sepsis Rats

目的:观察脓毒症心肌损伤大鼠超敏肌钙蛋白Ⅰ(High-sensitivity troponinⅠ,hsTnⅠ)、心肌过氧化物酶体增殖物激活受体γ辅激活因子1α(peroxisome proliferators-activated receptor-7coactivator-1α,PGC-1α)、微管相关蛋白1轻链3-Ⅱ(microtubule-associated protein l light chain 3B,LC3-Ⅱ)、雷帕霉素靶蛋白(mechanistic target of rapamycin,mTOR)及自噬效应蛋白Beclin-1的水平,探讨瑞舒伐他汀影响脓毒症心肌细胞自噬及减轻心肌损伤的机制。方法:24只清洁级健康雄性Wistar大鼠随机分成假手术组(Sham组)、脓毒症心肌损伤模型组(CLP组)、瑞舒伐他汀给药组(ROS组),每组8只。于手术后24 h分别检测hsTnⅠ、PGC-1α、LC3-Ⅱ、mTOR及Beclin-1浓度,光镜观察心肌组织病理变化。结果:三组术后24h hsTnⅠ、PGC-1α、LC3-Ⅱ、mTOR及Beclin-1浓度间有显著差异(P<0.05);与Sham组比较,术后24 h CLP、ROS组hsTnI [(1524.00±93.97 vs 309.50±31.80 pg/mL)(696.7.±52.61 vs 309.50±31.80 pg/mL)]、PGC-1α[(63.56±9.27 vs 15.92±4.49)(39.18±6.08 vs 15.92±4.49]、LC3-Ⅱ[(33.09±1.42 vs 17.83±1.47)(40.47±2.55 vs 17.83±1.47)]、mTOR[(29.72±2.15 vs17.33±1.13)(24.12±1.29 vs 17.33±1.13)]及Beclin-1[(30.48±1.86 vs 20.58±1.68)(41.09±3.22 vs 20.58±1.68)]浓度均升高,差异有统计学意义(P<0.01);与CLP组同期比较,ROS组hsTnⅠ(696.7±52.61 vs 1 524.00±93.97 pg/mL)、PGC-1α(39.18±6.08 vs 63.56±9.27)及mTOR (24.12±1.29 vs 29.72±2.15)浓度均明显下降,LC3-Ⅱ(40.47±2.55 vs 33.09±1.42)及Beclin-1 (41.09±3.22 vs 30.48±1.86)浓度升高,差异亦有统计学意义(P<0.05);光镜下CLP组和ROS组存在心肌损害,ROS组较CLP组心肌损伤有所减轻。结论:瑞舒伐他汀通过影响脓毒症心肌损伤时自噬因子水平,从而减轻心肌损伤。

Objective: To observe the levels of High-sensitivity troponin I(hsTnI), peroxisome proliferators-activated receptor-γcoactivator-1α(PGC-1α), microtubule-associated protein l light chain 3 B(LC3-II), mechanistic target of rapamycin(mTOR)and Beclin-1 released in septic rats, and to explore the mechanism of Rosuvastatin(ROS) on myocardial autophagy and the mechanism of reducing septic myocardial injury. Methods: A total of 24 male Wistar rats of clean grade were randomly divided into the sham-operation group(Sham), the sepsis model group(CLP), and the rosuvastatin treatment group(ROS), 8 rats in each group. Concentrations of hsTnI, PGC-1α, LC3-II, mTOR and Beclin-1 expression were detected in each group at 24 h after operation. Pathological changes of myocardium were observed under light microscope. Results: Concentrations of hsTnI, PGC-1α, LC3-II, mTOR and Beclin-1 at 24 h after operation were significantly different in the Sham, CLP and ROS group(P<0.05). Concentrations of hsTnI [(1524.00±93.97 vs 309.50±31.80 pg/mL)(696.7±52.61 vs 309.50±31.80 pg/mL)], PGC-1α [(63.56±9.27 vs 15.92±4.49)(39.18±6.08 vs 15.92±4.49)], LC3-II [(33.09±1.42 vs 17.83±1.47)(40.47±2.55 vs 17.83±1.47)], mTOR [(29.72±2.15 vs 17.33±1.13)(24.12±1.29 vs 17.33±1.13)] and Beclin-1 [(30.48±1.86 vs 20.58±1.68)(41.09±3.22 vs 20.58±1.68)] at 24 h after operation were significantly higher in the CLP and ROS group than those in the Sham group(P<0.01). Concentrations of hsTnI(696.7±52.61 vs1524.00±93.97 pg/mL), PGC-1α(39.18±6.08 vs 63.56±9.27) and mTOR(24.12±1.29 vs 29.72±2.15) at 24 h after operation were significantly lower, Concentrations of LC3-II(40.47±2.55 vs 33.09±1.42) and Beclin-1(41.09±3.22 vs 30.48±1.86) were significantly higher in the ROS group than in the CLP group(P<0.05). Myocardial injury occurred in the CLP and the ROS group under light microscope. And this injury was less severe in the ROS group than in the CLP group. Conclusion: Rosuvastatin could infect autophagic factor levels and reduce myocardial damage in septic rats.