【摘要】 目的:观察依托咪酯对心肌缺血再灌注(MI/R)大鼠心功能相关指标的影响。方法:将健康清洁级SD大鼠分为假手术组、MI/R组、依托咪酯低剂量组和依托咪酯高剂量组，每组15只。采用冠状动脉结扎法制备MI/R大鼠模型。依托咪酯低剂量组和依托咪酯高剂量组分别腹腔注射10、20 mg/kg依托咪酯，假手术组和MI/R组注射等体积生理盐水，每日1次，持续14 d。治疗结束后，观察各组大鼠心功能变化，酶联免疫吸附法(ELISA)检测血清肌酸激酶同工酶(CK-MB)、心肌肌钙蛋白I(cTnI)、乳酸脱氢酶(LDH)含量；苏木精-伊红(HE)染色检测心肌组织病理变化；末端脱氧核苷酸转移酶介导的dUTP缺口末端标记(TUNEL)染色检测心肌细胞凋亡情况，蛋白免疫印迹法(Western Blot)检测自噬相关蛋白表达，并测定各组大鼠脂代谢功能指标总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白胆固醇(HDL-C)含量及脂蛋白脂酶(LPL)、肝脂酶(HL)活性。结果:与假手术组比较，MI/R组大鼠射血分数(EF)和缩短分数(FS)降低，左室收缩末期内径(LVESD)、左室舒张末期内径(LVEDD)和CK-MB、cTnI、LDH含量升高，心肌组织出现明显的病理变化，TUNEL阳性细胞比例升高，Beclin-1蛋白表达上调，LC3-Ⅱ/LC3-Ⅰ比值升高，p62蛋白表达下调，TC、TG浓度升高，HDL-C浓度、LPL和HL含量降低，差异均有统计学意义(P<0.05)。与MI/R组比较，依托咪酯低剂量组、依托咪酯高剂量组EF和FS、HDL-C浓度、LPL和HL含量均升高，LVESD和LVEDD、TC、TG浓度和CK-MB、cTnI、LDH含量及TUNEL阳性细胞比例均下降，心肌组织病变得到明显改善，Beclin-1蛋白表达下调，LC3-Ⅱ/LC3-Ⅰ比值下降，p62蛋白表达上调，差异均有统计学意义(P<0.05)。结论:依托咪酯可改善大鼠MI/R损伤后心功能及脂代谢，减轻心肌损伤，其机制可能与抑制细胞过度自噬相关。更多还原

【Abstract】 Objective: To observe the effects of etomidate on cardiac function in rats with myocardial ischemia/reperfusion(MI/R) injury.Methods: The experiment was set up the sham group, MI/R group, etomidate low-dose group and etomidate high-dose group, with 15 rats in each group.The MI/R rat model was prepared by coronary artery ligation.The etomidate low-dose group and etomidate high-dose group were injected intraperitoneally with 10 mg/kg and 20 mg/kg etomidate, respectively, and the sham group and MI/R group were injected with equal volume of saline once a day for 14 days.After treatment, cardiac function changes were observed in each group of rats, and serum creatine kinase isoenzyme(CK-MB),cardiac troponin I(cTnI),and lactate dehydrogenase(LDH) were detected by enzyme-linked immunosorbent assay(ELISA);myocardial histopathological changes were detected by hematoxylin-eosin(HE) staining; terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling(TUNEL) staining was used to detect cardiomyocyte apoptosis; Western Blot was used to detect the expression of autophagy-related proteins, and the levels of total cholesterol(TC),triacylglycerol(TG),high-density lipoprotein cholesterol(HDL-C),the activities of lipoprotein lipase(LPL),and hepatic lipase(HL) were detected in rats of each group.Results: Compared with the sham group, the ejection fraction(EF) and shortening fraction(FS) of rats in the MI/R group decreased, the contents of left ventricular end-systolic diameter(LVESD),left ventricular end-diastolic diameter(LVEDD),CK-MB,cTnI and LDH increased.The myocardial tissue showed obvious pathological changes, and the proportion of TUNEL positive cells increased.Beclin-1 protein expression up-regulated, LC3-Ⅱ/LC3-Ⅰ ratio increased, p62 protein expression down-regulated, TC and TG increased, and HDL-C concentration, LPL and HL contents decreased(P<0.05).Compared with MI/R group, EF and FS,HDL-C concentrations, LPL and HL contents increased in the etomidate low-dose group and etomidate high-dose group, while LVESD and LVEDD,TC,TG concentrations and CK-MB,cTnI,LDH contents decreased, and the proportion of TUNEL positive cells significantly improved.Beclin-1 protein expression down-regulated, LC3-Ⅱ/LC3-Ⅰ ratio decreased, and p62 protein expression up-regulated(P<0.05).Conclusion: Etomidate could improve cardiac function and lipid metabolism after myocardial ischemia-reperfusion injury in rats, and alleviate myocardial injury.The mechanism might be related to inhibiting excessive autophagy of cells.更多还原