瓜蒌-薤白对异丙肾上腺素诱导心肌缺血大鼠MAPKs信号通路的影响

Effect of Trichosanthis Fructus and Allium Macrostemonis Bulbus on Myocardial Ischemia Induced by Isoproterenol in Rats via MAPKs Signaling Pathways

目的:探讨瓜蒌-薤白对心肌缺血损伤的保护作用机制。方法:SD大鼠分为6组:正常组,模型组,瓜蒌25 g·kg-1组,薤白12.5 g·kg-1组,瓜蒌-薤白37.5 g·kg-1组,阳性对照(普萘洛尔)0.02 g·kg-1组,每组9只,连续给药14 d。心肌缺血模型完成后,开始给药,采用连续6 d腹腔注射异丙肾上腺素0.04 mg·kg-1制造大鼠心肌缺血模型,给药14 d后,分离血清检测超氧化物歧化酶(SOD)活性、丙二醛(MDA)以及血清肌酸激酶(CK)、乳酸脱氢酶(LDH)含量。采用Western blotting法观测瓜蒌-薤白对有丝分裂原活化蛋白激酶(MAPKs)家族3个主要信号分子C-Jun氨基端激酶(JNK)、细胞外信号调节激酶(ERK)、p38磷酸化水平的影响。结果:与正常组相比,模型组大鼠血清中LDH,CK和MDA水平明显升高,SOD活性显著下降(P<0.05,P<0.01),与正常组相比,模型组P-p38 P-JNK P-ERK明显上调(P<0.05,P<0.01)。与模型组比较瓜蒌,薤白,瓜蒌-薤白能显著降低血清中MDA,CK,LDH含量,瓜蒌-薤白降幅最大,与瓜蒌,薤白组比较有显著性差异(P<0.01)。瓜蒌-薤白组P-p38,P-JNK,P-ERK水平显著降低。结论:瓜蒌-薤白对心肌缺血损伤有保护作用,其机制可能是通过清除氧自由基、减轻氧化反应而抑制p38,JNK,ERK蛋白磷酸化以减轻缺血损伤,对心肌具保护作用。

Objective：To explore the protective of Trichosanthis Fructus and Allium Macrostemonis Bulbus on myocardial ischemic injury and its mechanism in rats.Method：Sprague Dawley rats were divided into 6 groups.The models of chronic myocardial ischemia was established by intraperitoneal injection of isoproterenol.After two weeks,activity of superoxide dismutase （SOD）,levels of lactate dehydrogenase （LDH）,creatine kinase （CK） and malondialdehyde （MDA） were measured.Western blotting was used to assay effects of Trichosanthis Fructus and Allii Macrostemonis Bulbus on mitogen-activated protein kinase （MAPKs） family of 3 major signaling molecule c-Jun n-Terminal kinase （JNK）,extracellular signal-regulated kinase （ERK）,phosphorylation of p38.Result：Compared with normal group,LDH,CK and MDA of model group increased significantly,SOD decreased significantly （P 〈 0.05,P 〈 0.01）.Compared with normal group,P-p38 P-JNK P-ERK of model group was significantly increased （P 〈 0.05,P 〈 0.01）.TKAM can significantly decrease the content of MDA,CK,LDH in serum.P-p38,P-JNK,P-ERK,MAPK protein levels of ischemia myocardial tissue increased significantly,TKAM can effectively lower levels of P-p38,P-JNK,P-ERK.Conclusion：Trichosanthis Fructus and Allium Macrostemonis Bulbus has a good protective effect on myocardial ischemia injury.The mechanism may be adopted on scavenging oxygen free radicals,reduce the oxidation inhibition of p38 and JNK phosphorylation of proteins in order to reduce ischemic injury.