丝裂原活化蛋白激酶p38的激活在四逆汤预处理诱导大鼠心肌延迟预适应中的作用

Pretreatment with Sini decoction induces delayed preconditioning in rat heart and role of p38 MAP kinase

目的 :探讨四逆汤能否诱导心肌延迟预适应及其机制。方法 :SD大鼠分为正常对照组、假手术组、缺血再灌注 (I/R)组、延迟缺血预处理组、四逆汤预处理组。延迟缺血预处理组采用经典大鼠冠脉结扎 ,缺血 5min ,再灌 5min ,反复循环 3次 ,2 4h后缺血 1h ,再灌 1h。四逆汤预处理组给予四逆汤灌胃 (5mL·kg-1·d-1)连续 3d ,末次灌药 2 4h后缺血 1h ,再灌 1h。以心肌梗死面积、心肌酶为评价指标 ,测定心肌中NO2 -/NO3 -的含量并通过免疫组化检测大鼠心肌p38MAPK及PKC的表达。结果 :延迟缺血预处理组及四逆汤预处理组心肌梗死面积、血清CK、LDH的值明显少于I/R组 ,NO2 -/NO3 -含量显著高于I/R组 ,p38MAPK和PKC发生转位且蛋白表达明显高于I/R组。结论 :四逆汤能诱导心肌延迟预适应 ,其机制与p38MAPK的激活可能有关。

AIM: The present study was designed to determine whether Sini decoction (SND), a traditional Chinese medicine, induces delayed preconditioning-like effect in rat heart and the possible mechanism by which ischemia myocardium is protected. METHODS: Sprage-Dawleyt rats underwent three 5 min episodes of preconditioning ischemia 24 h prior to the global ischemia and reperfusion in ischemic preconditioning/second window of protection (IPC/SWOP) group or were pretreated with Sini decoction (5 mL·kg -1 ·d -1 for 3 days, the last treatment 24 h before global ischemia and reperfusion) in SND group. Myocardial infarct size, CK, LDH and NO were examined. p38 MAPK and PKC were determined by immunohistochemisty. RESULTS: Myocardial infarct size was significantly decreased, CK and LDH were decreased in the serum, NO 2 -/NO 3 - was increased in myocardial tissue in SND group as well as in IPC/SWOP group (there was no difference between the two groups). The expression of p38 MAPK and PKC were upregulated in myocardial tissue in SND and IPC/SWOP groups. CONCLUSION: These results suggest that Sini decoction induces delayed preconditioning-like effect in the rat heart, possibly via inducing p38 MAPK activation.