解毒通络方对大鼠心肌纤维化的影响及作用机制  

Effects and Mechanism of Jiedu Tongluo Formula on Myocardial Fibrosis in Rats

作　　者：王健康[1] 刘智[1] 袁颢 苏文龙 郭家娟[2] WANG Jian-kang;LIU Zhi;YUAN Hao;SU Wen-long;GUO Jia-juan(Changchun University of Chinese Medicine,Changchun 130117,China;Affiliated Hospital of Changchun University of Chinese Medicine,Changchun 130021,China)

机构地区：[1]长春中医药大学,吉林长春130117 [2]长春中医药大学附属医院,吉林长春130021

出　　处：《中药材》2024年第1期176-182,共7页Journal of Chinese Medicinal Materials

基　　金：国家自然科学基金青年科学基金项目(81503544);国家青年岐黄项目;吉林省自然科学基金项目(YDZJ202301ZYTS163);吉林省创新创业人才项目(2023QN22)。

摘　　要：目的:基于氧化应激和NF-κB探讨解毒通络方对异丙肾上腺素(ISO)所诱导大鼠心肌纤维化的影响及作用机制。方法:将雄性Wistar大鼠随机分为正常对照组、模型组、卡托普利(5 mg/kg)阳性对照组及解毒通络方低(1.8 g/kg)、中(3.6 g/kg)、高(7.2 g/kg)剂量组。除正常对照组外,其余各组大鼠均采用皮下注射ISO(5 mg/kg)连续7 d的方法建立大鼠心肌纤维化模型,造模成功后第2天开始灌胃,连续28 d。HE、Masson染色观察大鼠心肌组织病理改变和胶原纤维沉积;DHE染色观察各组大鼠心肌组织ROS表达;碱水法检测大鼠心肌组织中HYP水平;ELISA法检测大鼠血清LDH、CK-MB水平;试剂盒检测大鼠血清和心肌组织中氧化应激指标;qPCR和Western Blot检测大鼠心肌组织NF-κBP65、TGF-β_1、CTGF mRNA及蛋白和Smad2/3、CollagenⅠ、CollagenⅢ蛋白表达。结果:与模型组比较,各给药组大鼠心肌结构紊乱和胶原纤维沉积明显改善,心肌组织中ROS及心脏指数和心肌损伤标志物LDH、CK-MB水平显著降低,血清及心肌组织SOD、GSH水平显著升高,MDA水平显著降低,心肌组织NF-κBP65、TGF-β_1、CTGF mRNA及蛋白和Smad 2/3、CollagenⅠ、CollagenⅢ蛋白表达显著降低。结论:解毒通络方能有效缓解ISO诱导的心肌纤维化大鼠心肌结构紊乱和间质胶原纤维化沉积,其作用机制可能与抗氧化应激和抑制NF-κB信号通路有关。Objective:To explore the effect and mechanism of Jiedu tongluo formula on isoprenaline(ISO)-induced myocardial fibrosis in rats based on oxidative stress and NF-κB.Methods:The male Wistar rats were randomly divided into normal control group,model group,captopril(5 mg/kg)positive control group,Jiedu tongluo formula low(1.8g/kg),medium(3.6 g/kg)and high(7.2 g/kg)dose groups.Except for the normal control group,the rat myocardial fibrosis model was established by subcutaneous injection of ISO(5 mg/kg/d)for 7 days.Intragastric administration was started on the second day after successful modeling and continued for 28 days.HE staining and Masson staining were used to observe the pathological changes of myocardial tissue and collagen fiber deposition.The expression of ROS in myocardial tissue was observed by DHE staining.The level of HYP in myocardial tissue of rats was detected by alkaline water method.Serum LDH and CK-MB levels were detected by Elisa.The oxidative stress indexes in serum and myocardial tissue of rats were detected by the kit.The expressions of NF-κBP65,TGF-β1,CTGF mRNA and proteins,Smad2/3,CollagenⅠ,CollagenⅢproteins in myocardial tissue of rats were detected by qPCR and Western Blot.Results:Compared with model group,the myocardial structure disorder and collagen fiber deposition were improved in eaeh administration group.ROS in rat myocardium and the cardiac index,myocardial injury markers LDH,CK-MB levels were significantly decreased,the SOD,GSH levels in rat serum and myocardium were significantly increased,MDA level was significantly decreased.The expressions of NF-κBP65,TGF-β1,CTGF mRNA and proteins and Smad 2/3,CollagenⅠ,CollagenⅢproteins were significantly decreased.Conclusion:Jiedu tongluo formula can effectively relieve myocardial structure disorder and interstitial collagen fibrotic deposition induced by ISO-induced myocardial fibrosis in rats,and its mechanism may be related to anti-oxidative stress and inhibition of NF-κB signaling pathway.

关 键 词：解毒通络方 心肌纤维化 异丙肾上腺素 氧化应激 NF-κB 

分 类 号：R285.5[医药卫生—中药学]