阻断p38MAPK信号通路对肝脏缺血再灌注损伤保护作用的机制研究

Research about the protection of blocking p38MAPK pathway to the liver ischemia reperfusion injury

目的探讨P38丝裂原活化蛋白激酶(p38MAPK)特异性活性抑制剂(FR167653)对大鼠肝脏缺血再灌注损伤保护作用的机理。方法利用封闭群SD大鼠肝脏部分缺血再灌注模型,将实验动物分假手术组、对照组、治疗组。分别在各个时间点按照相应程序采集标本检测肝组织髓过氧化物酶(MPO)活性、免疫组化检测黏附分子表达及肝组织诱生型一氧化氮合酶i NOS m RNA表达测定。结果肝脏缺血再灌注损伤后,对照组肝脏组织中MPO活性增高,而治疗组肝脏组织MPO活性明显低于对照组(t分别=3.30、3.10、4.10、2.90,P均<0.05);同时在治疗组中炎性趋化因子的表达也较对照组明显减低(t分别=3.70、4.30、4.60、4.90、3.50、4.00,P均<0.05)。免疫组化结果显示对照组肝组织内可见P-选择素(P-selectin)及细胞间黏附分子-1(ICAM-1)在肝组织中表达,而治疗组表达阳性率明显低于对照组;i NOS的m RNA表达水平在3 h和6 h时治疗组明显低于对照组(t分别=4.50、5.70,P均<0.05)。结论 FR167653能在多个环节、多个层次对缺血再灌注肝脏起着保护作用。

Objective To research the protection of p38MARK inhibitor FR167653 to the liver ischemia reperfusion in-jury in rats. Methods Liver ischemic reperfusion injury models of SD rats were structured and divided into sham operation group, control group and treatment group. Samples were harvested and used for detecting immunohistochemistry, activity of MPO and iNOS mRNA. Results After liver ischemic reperfusion injury, the activity of MPO in control group increased which was significantly higher than that in treatment group （t=3.30, 3.10,4.10,2.90,P〈0.05）. Meanwhile, the expression of chemokine in treatment group was significantly lower than control group （t=3.70, 4.30, 4.60,4.90,3.50,4.00,P〈0.05）. P-selectin and ICAM-1 were expressed dispersedly in the hepatic tissue after ischemic reperfussion injury in control group which were significantly higher than treatment group. In the control group, the expression of iNOS mRNA at 3-hour and 6-hour were significantly higher than treatment group（t=4.50,5.70,P〈0.05）. Conclusion FR167653 can protect liver from ischemia reperfusion injury.