p38 MAPK抑制剂对脓毒症大鼠肝损伤的保护作用

The protection of p38 MAPK inhibitor against hepatic injury in septic rats

目的探讨脓毒症肝损害的原因及p38丝裂原活化蛋白激酶(MAPK)抑制剂的保护作用。方法采用盲肠结扎并穿刺(CLP)来制作脓毒症模型。在不同时相点观察大鼠肝功能[谷丙转氨酶(ALT)]、血清肿瘤坏死因子-α(TNF-α)、白介素-1β(IL-1β)浓度。结果CLP术后血清TNF-α、IL-1β进行性升高,ALT也显著升高。血清ALT、TNF-α、IL-1β呈显著正相关。应用p38MAPK抑制剂SB203580后,血清TNF-α、IL-1浓度显著降低,同时血ALT减低。结论TNF-α、IL-1的大量释放是脓毒症肝损害的原因之一,通过调控p38MAPK信号通路可对脓毒症鼠肝损害起保护作用。

Objective To investigate the reason of hepatic injury and the protection of p38 MAPK inhibitor against hepatic injury in sepsis. Methods The cecal ligation and puncture was adopted to build sepsis model The level of serum ALT,TNF - alpha and IL - 1beta at different time points were observed. Results The level of ALT, TNF - alpha and IL - 1 beta increased progrossively after the CLP operation. The level of TNF - alpha and IL - 1 beta have a significant correlation with ALT. After administering p38MAPK inhibitor, SB203580, the level of TNF - alpha and IL - 1 beta were found to decrease evidently, and the hepatic injury was alleviated. Conclusion TNF - alpha and IL - 1 beta secreted exces- sively are the main cause of hepatic injury in sepsis. The regnlation of the p38MAPK pathway may protect hepatic injury in sepsis.