麝香保心丸通过调节apelin/APJ信号转导通路减轻大鼠心肌缺血/再灌注损伤后心功能异常的实验研究

Shexiang Baoxin Pill Attenuates Cardiac Dysfunction after Myocardial Ischemia-reperfusion Injury through Regulating apelin/APJ Signaling Pathway

目的探讨麝香保心丸对大鼠心肌缺血/再灌注损伤后心功能保护作用及相关机制。方法将36只Wistar大鼠分为正常对照组、模型组、麝香保心丸组,每组12只。麝香保心丸组给予麝香保心丸50mg/(kg·d),共30d,正常对照组及缺血再灌注组给予同等剂量的生理盐水,在最后一天制备心肌缺血/再灌注模型。在实验结束后24h后,检测大鼠心功能、乳酸脱氢酶(LDH)、肌酸激酶同工酶(CK-MB)、血浆及心肌apelin水平。应用western-blot检测心肌apelin及APJ蛋白的表达。结果与模型组比较,麝香保心丸预处理可明显提高大鼠心肌缺血/再灌注损伤后心功能。病理学结果提示麝香保心丸可显著减轻心肌损伤后导致的肌纤维坏死及炎症细胞的浸润。与模型组比较,麝香保心丸组的CK-MB与LDH明显降低,同时麝香保心丸可使心肌及血浆apelin含量明显升高。模型组apelin和APJ的蛋白表达较正常对照组明显降低,然而麝香保心丸治疗可以逆转这一改变。结论麝香保心丸预处理可以保护大鼠心肌缺血/再灌注损伤后心功能减低,这一保护作用可能是通过调节apelin/APJ信号转导通路表达来实现的。

Objective To investigate the protective effects of Shexiang Baoxin pill（SBP）on cardiac function after myocardial ischemiareperfusion（I/R）injury in rats and the probable mechanism.Methods Thirty-six wistar rats were randomly divided into 3 groups：control group（n =12）,I/R group（n =12）,SBP group（n =12）.The rats in SBP group was once a day treated for 30 days,and the rats in control group and I/R group were given the same dose of saline.I/R model was induced at last day.after 24 h of induction,the heart function,histological changes,lactate dehydrogenase（LDH）,creatine kinase-MB（CK-MB）,apelin levels both in plasma and myocardium were observed.The levels of apelin and APJ protein expression in the cardiac tissues were measured by western-blot.Results Compared with the model group,pretreatment with SBP markedly improved cardiac function after myocardial I/R injury in rats.Histopathological results showed that SBP treatment significantly reduced myocardial fibers necrosis and inflammatory cells infiltration induced by I/R injury.The levels of CK-MB and LDH were obvious decreased in SBP group,compared with that in the model group,while the apelin levels in plasma and myocardium were increased.Compared with the control group,the protein expressions of apelin and APJ were obviously reduced in the I/R group,however,SBP could reverse the changes.Conclusion Pretreatment with SBP has protective effect against cardiac dysfunction after myocardial I/R injury in rats,and the mechanism may be associated with regulation of apelin/APJ signaling pathway.