不同类型β受体阻滞剂对脓毒症大鼠早期心肌损伤的影响

Effect of different beta-adrenergic blockers on the early myocardial damage in septic rats

目的 探讨不同类型β受体阻滞剂对脓毒症大鼠早期心肌损伤的影响及其可能机制.方法 96只健康雄性SD大鼠随机分为假手术组（Sham组）、脓毒症组（CLP组）、美托洛尔治疗组（M组）、普萘洛尔治疗组（P组）四组.采用盲肠结扎穿孔（CLP）法建立脓毒症模型,分别采用生理盐水或美托洛尔、普萘洛尔注射液于术后2 h腹腔注射,并于术后3、6、12、24 h（每个时相点6只大鼠）取腹主动脉血及左室心肌,测定血清心肌肌钙蛋白I（cTnI）及心肌组织匀浆上清液中超氧化物歧化酶（SOD）、丙二醛（MDA）水平,观察心肌组织病理改变;采用DNA切口末端标记法（TUNEL）染色检测心肌细胞凋亡,共聚焦显微镜观察心肌细胞凋亡.结果 与Sham组比较,CLP组大鼠血清cTnI、心肌细胞凋亡指数（AI）、心肌组织匀浆上清液MDA显著升高,SOD显著降低（P〈0.05）;与CLP组比较,M、P组除SOD显著升高（P〈0.05）外,其余指标均显著降低（P〈0.05）;P组较M组 SOD显著增高,MDA显著降低（P〈0.05）.结论 β受体阻滞剂对脓毒症早期心肌损伤具有保护作用,这种有益效应与拮抗交感神经活性、减少心肌细胞凋亡及减轻心肌细胞氧化应激损伤有关,且非选择性β受体阻滞剂普萘洛尔在抗氧化应激方面优于选择性β1受体阻滞剂美托洛尔.

Objective To investigate the interventionaJ effect and it＇s possible mechanism of different beta - adrenergic blockers on the early myocardial damage in septic rats. Methods 96 male Sprague - Dawley （SD） rats were randomly divided into 4 groups ： the sham group （ n = 24）, the cecal ligation and puncture group （ CLP group, n = 24 ）, the metoprolol group （ M group, n = 24 ）, the propranolol group （ P group, n = 24 ）. Cecal ligation and puncture （CLP） was adopted to reprnduce animal model of sepsis. The contents of serum cTnI and TNF - ct were detected in each group at 3, 6, 12, 24 hours after the operation, as well as activities of SOD and MDA in myocardium from the left ventricle. The changes of myocardial pathomorphology by HE and myocardial cells apoptosis by TUNEL were observed through the microscope. The myocardial cells apoptosis was detected by con_focal microscopy. Results The level of serum cTnI and the apoptosis index of myocardial in sepsis group was much higher than that in sham group at each point time after CLP （ P 〈 0.05 ）. At the same time, the activity of MDA in myocardium in sepsis group was much higher than that in sham group （ P 〈 0.05 ）, hut the activities of SOD was much lower （ P 〈 0.05 ）. In the M and P groups, the indexes above - mentioned were lower than CLP group （ P 〈 0.05 ）, except that activity of SOD was higher （ P 〈 0.05 ）.The level of SOD in P group was much higher than that in M group at each time point after CLP （ P 〈 0. 05 ）, but the level of MDA was much lower （ P 〈 0.05 ）. Conclusion The beta - adrenergic blockers of metoprolol and propranolol can protect myocardium from the damage resulted from sepsis in a rat model, probably by decreasing myocardial apoptosis and depressing activity of sympathetic nervous. In addition, an extra cardioprotection role of the beta - adrenergic blockers may be also associated with their antioxidant effects. Propranolol （non -selective beta- adrenergic blocker） has a better protective effect of antioxidation than metoprolol （β1 -selective beta- adrenergic blocker）.