乌司他丁和胸腺肽α1对脓毒症大鼠心肌的保护作用

The protective effect of ulinastatin and thymosin α1 against myocardial damage in septic rats

目的探讨乌司他丁和胸腺肽α1单独及联合用药对脓毒症大鼠心肌的保护作用。方法 40只雄性SD大鼠采用盲肠结扎穿刺法制造脓毒症模型后,随机分为4组,分别为联合治疗组、胸腺肽组、乌司他丁组及对照组,制模成功后分别给予乌司他丁联合胸腺肽α1、乌司他丁单独、胸腺肽α1单独和生理盐水处理。通过心脏彩超观察大鼠心功能变化,取心肌组织分别检测各组磷酸化p38丝裂原活化蛋白激酶(p38 MAPK)、肿瘤坏死因子-α(TNF-α)、一氧化氮(NO)水平,组织切片行HE及Hoechst 33258染色观察细胞形态及凋亡数量。结果相比对照组,乌司他丁和胸腺肽α1单独、联合使用均能降低脓毒症大鼠心肌细胞磷酸化p38 MAPK、TNF-α、NO水平,增加心脏EF值,降低凋亡细胞比例,差异具有统计学意义(P<0.05),其中联合用药效果最强。结论乌司他丁和胸腺肽α1联合用药可能通过抑制p38 MAPK途径减轻脓毒症大鼠心肌损害,减少细胞凋亡,效果较单独用药增强。

Objective To investigate the effect of ulinastatin combined with thymosin α1, ulinastatin alone and thy-mosin α1 alone against myocardial damage in septic rats. Methods Forty male SD rats were randomized into four groups, ulinastatin combined with thymosinα1 group, thymosinα1 group, ulinastatin group and control group. Cecal ligation and punc-ture operation were performed on the four groups to produce animal model of sepsis. Thymosin α1 combined with ulinastatin, thymosin α1 alone, ulinastatin alone and normal saline were given to the four groups after the operation respectively. Echocar-diography was performed to evaluate the indexes of cardiac function. The tissues of myocardium were harvested and the tissular concentration of the activated p38 mitogen-activated protein kinases, tumor necrosis factor-α and nitric oxide were measured. After HE and Hoechst 33258 stain, tissue sections were observed to evaluate the change of histomorphology and the proportion of apoptotic cells (P<0.05). Results In the ulinastatin combined with thymosin α1 group, thymosin α1 group and ulinastatin group, the concentrations of the activated p38 mitogen-activated protein kinases, tumor necrosis factor-α and nitric oxide were lower than those in the control group. In those groups, the EF values were higher and proportions of apoptotic cells were lower than those in the control group. The difference was statistically significant (P<0.05). The combinative therapy of two drugs was the most effective. Conclusion Ulinastatin combined with thymosinα1 may prevent myocardial damage induced by sepsis through inhibiting the p38 MAPK pathway, reduce cell apoptosis, it is more effective than the single drug therapy.