p38MAPK信号通路在清热解毒通腑液保护大鼠脓毒症心肌损伤中的作用

目的探讨清热解毒通腑中药液对脓毒症大鼠心肌损伤的作用及其可能机制。方法采用盲肠结扎穿孔法（CLP）制备脓毒症动物模型。180只雄性wistar大鼠，随机分为对照组（control）60只、脓毒症组（sepsis）60只、治疗组（treatment）60只。治疗组从造模前96小时（96h）开始按10ml/（kg-1·d-1）灌胃给予清热解毒通腑中药液，脓毒症组及对照组按相同方法予等量0.9％氯化钠注射液。分别于造模后3h ，6h ，12h ，24h ，48h ，72h六个时间点检测各亚组大鼠心功能、血清炎症因子（TNF-a、IL-6、IL-10）、心肌p38丝裂原活化蛋白激酶（p38mitogen-activated protein kinase ，p38MAPK ）等指标。结果与对照组比较，脓毒症组在造模后3h心肌p38MAPK磷酸化水平出现升高并达高峰（ P＜0.01）；血清炎症因子在3h出现升高（ P＜0.05），其中TNF-a在造模后3h达高峰（ P＜0.01），IL-6于造模后12h达高峰（ P＜0.01）；心功能指标从3h即出现下降（ P＜0.05），至12h下降最明显（ P＜0.01）。与脓毒症组比较，治疗组各项指标均有所改善（ P＜0.05）。结论清热解毒通腑中药液对脓毒症大鼠心肌损伤具有保护作用，其作用机制可能是通过p38MAPK信号途径，调控机体免疫炎症反应，从而对脓毒症大鼠心肌损伤起到保护作用。

Effects of p38MAPK on Heat_clearing and Detoxicating Drug in Septic Rats with Myocardial Injury

Objective To investigate the effects of p38MAPK on heat-clearing and detoxicating drug in septic rats with myocardial in-jury and the possible mechanism.Methods Male adult rats were subjected to sepsis by cecal ligation and puncture （CLP）.Total 180 male adult wistar rats were randomly divided into control group （n=60） ,sepsis group（n=60） and treatment group（n=60）.The rats in treatment group were pretreated with decoction by 10ml/（kg-1 ·d-1 ） 96h before CLP ,and rats in other two groups were pretreated with normal saline in the same way.Cardiac function was assessed at 3h ,6h ,12h ,24h ,48h and 72h after CLP or sham surgery ,and the detections of the level of phosphorylation of p38MAPK、the level of inflammatory cytokines （TNF-a ,IL-6 ,IL-10） were tested re-spectively. Results Compared with control group ,the expression of p38MAPK protein are increased significantly and peaked 3h after the surgery （ P〈0.01 ） ,cardiac function in sepsis group decreased significantly since 3h after the surgery ,while a remarkable de-crease could be observed at post-challenge of 12h（ P〈0.01）;serum inflammatory factors including TNF-a ,IL-6 in sepsis group in-creased significantly since 3h after the surgery. TNF-a reached peaked at 3h （ P〈0.01 ） ,the IL-6 reached peaked at 12h （ P〈0.01） . Compared with sepsis group , cardiac function ,the level of inflammatory cytokines and the level of phosphorylation of p38MAPK were all improved in treatment group. Conclusions Heat-clearing and detoxicating drug may decrease myocardial injury in septic rats.Further ,p38MAPK signaling pathway may play an important role through regulating the inflammation reaction during sepsis .