p38MAPK抑制剂SB203580对脓毒症大鼠心功能的影响及机制探讨

Effect of p38MAPK inhibitor SB203580 on cardiac function of rats with sepsis

目的探讨丝裂原活化蛋白激酶p38MAPK抑制剂SB203580对脓毒症大鼠心功能的影响及其机制。方法 30只雄性SD大鼠随机分为对照组、模型组、干预组,各10只。模型组和干预组采用盲肠结扎穿刺术(CLP)制备脓毒症大鼠模型。干预组给予p38MAPK抑制剂SB203580干预。干预后1、3、6、12、24 h检测各组血清肿瘤坏死因子α(TNF-α)、IL-6水平,24 h后行心脏彩超检测各组大鼠的左室射血分数(EF)及短轴缩短率(FS);并分离左室心肌采用Western blot方法检测p38MAPK蛋白表达。结果模型组、干预组术后血清TNF-α、IL-6水平迅速升高,于24 h到达高峰,但干预组升高幅度小于模型组(P均<0.05)。术后24 h模型组、干预组左心室EF和FS较对照组显著降低(P均<0.05)。干预组左心室EF和FS下降程度小于模型组(P均<0.05)。与对照组比较,术后24 h模型组、干预组心肌组织中p38MAPK蛋白相对表达量升高,干预组低于模型组(P均<0.05)。结论 p38MAPK抑制剂SB203580对脓毒症大鼠心功能有保护作用,降低TNF-α、IL-6水平可能为其主要机制。

Objective To investigate the effect of mitogen-activated protein kinase p38MAPK inhibitor SB203580 on cardiac function of rats with sepsis and its mechanism.Methods Thirty male SD rats were randomly divided into the control group,model group and intervention group,10 in each group.Rat models of sepsis in the model and intervention groups were established by cecal ligation and puncture （CLP）,and the intervention group was given p38MAPK inhibitor SB203580.The levels of tumor necrosis factor-α （TNF-α） and IL-6 were determined at 1,3,6,12 and 24 h after the intervention.At 24 h after successful modeling,the left ventricle ejection fraction （LVEF） and fractional shortening （LVFS） were evaluated by echocardiography,and the myocardium of the left ventricle was isolated to examine the expression of the p38MAPK by using Western blotting.Results The serum levels of TNF-α and IL-6 increased rapidly,reached a peak at 24 h in the model group and intervention group,but the intervention group increased less than the model group （all P ＜ 0.05）.At 24 h after successful modeling,the left ventricular EF and FS of the model group and intervention group significant reduced as compared with those of the control group （all P ＜ 0.05） ; the protein expression of p38MAPK in myocardial tissue of the model group and intervention group progressively increased as compared with that of the control group,and the intervention group was lower than the model group （all P ＜0.05）.Conclusion p38MAPK inhibitor SB203580 has a protective effect on cardiac function of rats with sepsis,and the decrease of TNF-α and IL-6 levels is considered as its main mechanism.