美托洛尔对脓毒症大鼠心肌细胞凋亡的影响

目的:探讨美托洛尔对脓毒症大鼠心肌细胞凋亡的抑制作用及机制。方法:72只大鼠随机分为对照组(n=24)、脓毒症组(n=24)及治疗组n=24,脓毒症模型基础上美托洛尔0.05mg冲击量后0.2mg/(kg·h)静脉泵入]。于术后3、6、12、24h测定血清肿瘤坏死因子-α(TNF-α),心肌髓过氧化物酶(MPO)和半胱氨酸天冬氨酸酶-3(caspase-3)活性,TUNEL法检测心肌细胞凋亡,光镜下观察心肌组织病理改变。结果:脓毒症组和治疗组大鼠各时点血浆TNF-α,心肌MPO、caspase-3活性、心肌细胞凋亡指数均较对照组显著升高(P<0.05),以术后12h最显著。应用美托洛尔后,上述指标与脓毒症组各时点相比均有不同程度降低,其中血浆TNF-α和心肌MPO活性在12、24h有统计学差异(P<0.05),心肌caspase-3活性和心肌细胞凋亡指数在6、12和24h有统计学差异(P<0.05),且心肌损害病理改变较脓毒症组显著减轻。结论:美托洛尔具有对抗脓毒症大鼠心肌细胞凋亡的作用,可能与抑制细胞因子、减轻心肌炎症反应、降低caspase-3活性有关。

Inhibition of metoprolol on myocardial apoptosis in rats with sepsis

Objective To investigate the role and mechanisms of metoprolol on myocardial apoptosis in rats with sepsis.Methods Seventy-two rats were randomly divided into control group(n=24),sepsis group (n=24) and treatment group (for sepsis models,intravenous pump infusion with metoprolol 0.2 mg/(kg·h),n=24).At 3,6,12,24 h after the operation,the serum TNF-α,cardiomyocytes activity of MPO and caspase-3 were tested,cardiomyocytes apoptosis index and myocardial pathomorphology by optical microscope were assessed.Results The serum TNF-α,activity of MPO and caspase-3,cardiomyocytes apoptosis index were increased significantly in the sepsis group and treatment group as compared with the control group (P<0.05),especially at the 12 h.After using metoprolol,the serum TNF-α and the activity of MPO at the 12 and 24 h,the activity of caspase-3 and the cardiomyocytes apoptosis index at the 6,12 and 24 h decreased significantly as compared with the sepsis group(P<0.05),meanwhile myocardial pathomorphology damage was alleviated in treatment group.Conclusions Metoprolol can inhibit myocardial apoptosis in rats with sepsis.The decreases in cytokine,myocardial inflammatory reaction and the activity of caspase-3 are probably the mechanism of anti-apoptosis.