抵当陷胸汤对糖尿病大鼠心肌超微结构和CTGF及其受体LRP蛋白表达的影响  

Effect of Didang Xianxiong Decoction on Myocardium Ultrastructure and Expression of CTGF and Its Receptor LRP in Diabetic Rats

作　　者：蔡正银[1] 储俊[1,2] 储全根[1,2] 轩云 程婕 王盼 CAI Zhengyin;CHU Jun;CHU Quangen;XUAN Yun;CHENG Jie;WANG Pan(Anhui University of Chinese Medicine,Hefei 230038,China;Key Laboratory of Xin'an Medicine,Ministry of Education,Anhui University of Chinese Medicine,Hefei 230038,China)

机构地区：[1]安徽中医药大学,合肥230038 [2]安徽中医药大学新安医学教育部重点实验室,合肥230038

出　　处：《中国实验方剂学杂志》2022年第22期100-105,共6页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家自然科学基金项目(81774189);安徽省中医药领军人才项目。

摘　　要：目的:观察抵当陷胸汤对糖尿病心肌病(DCM)大鼠心肌超微结构的影响,并同时探究其对结缔生长因子(CTGF)及其低密度脂蛋白受体相关蛋白(LRP)表达的影响。方法:给予链脲佐菌素(55 mg·kg^(-1))腹腔注射大鼠建立糖尿病模型,继续饲养3周,即DCM模型。将造模成功40只大鼠随机分为模型组、小陷胸汤组、血府逐瘀汤组、抵当陷胸汤组和阿拉氯胺(ALT-711)组,每组8只大鼠,另随机选10只正常健康大鼠设为正常组。给药组按剂量为4.05、6.30、8.10 g·kg^(-1)·d^(-1)和3 mg·kg^(-1)·d^(-1)灌胃相应药物;正常组及模型组均按照10 mL·kg^(-1)·d^(-1)剂量给予蒸馏水灌胃8周,第8周末麻醉状态下取心肌组织。采用透射电镜观察心肌细胞的超微结构;采用免疫组化和蛋白免疫印迹法(Western blot)检测心肌组织中CTGF及其受体LRP蛋白表达。结果:与正常组比较,模型组的心肌超微结构损伤明显,CTGF蛋白表达水平显著增高(P<0.01),LRP蛋白表达水平差异无统计学意义。与模型组比较,各给药组心肌超微结构均有不同程度的改善,给药组CTGF蛋白表达水平均显著下调(P<0.01),而LRP蛋白表达水平差异无统计学意义;且抵当陷胸汤组的心肌超微结构改善效果与CTGF的蛋白下降水平较小陷胸汤组与血府逐瘀汤组效果好(P<0.01)。结论:抵当陷胸汤可能通过降低糖尿病大鼠心肌组织CTGF的高表达从而保护心肌组织,延缓心肌组织的纤维化,同时说明痰瘀同治效果优于单纯的化痰法与单纯化瘀法。Objective:To observe the effect of Didang Xianxiong decoction on the ultrastructure of myocardium and the expression of connective tissue growth factor(CTGF)and low-density lipoprotein receptorrelated protein(LRP)in diabetic rats.Method:The diabetic rat model was established by the intraperitoneal injection of high-dose streptozotocin(55 mg·kg^(-1))and the rats were further fed for 3 weeks.Forty model rats were randomly assigned into model group,a Xiao Xianxiongtang(4.05 g·kg^(-1)·d^(-1))group,Xuefu Zhuyutang(6.30 g·kg^(-1)·d^(-1))group,Didang Xianxiong decoction(8.10 g·kg^(-1)·d^(-1))group,and alagebrium chloride(ALT-711,3 mg·kg^(-1)·d^(-1))group,with 8 rats in each group.Ten normal healthy rats were randomly selected as the blank group.The corresponding drugs were administrated by gavage,and the blank group and the model group were given distilled water at a dose of 10 mL·kg^(-1)·d^(-1) for 8 weeks.The myocardial tissue was collected from the rats under anesthesia at the end of the 8^(th) week for pathological examination.The expression of CTGF and its receptor LRP in the myocardial tissue was detected by immunohistochemistry and Western blot.Result:Compared with the blank group,the modeling led to obvious ultrastructural damage of the myocardium,upregulated the expression of CTGF(P<0.01),and did not significantly change the expression of LRP.Compared with the model group,the drugs alleviated the damage in myocardium ultrastructure,down-regulated the expression of CTGF(P<0.01),and did not significantly change the expression of LRP.Moreover,Didang Xianxiong decoction showed better performance than Xiao Xianxiongtang and Xuefu Zhuyutang(P<0.01).Conclusion:Didang Xianxiong decoction may protect myocardial tissue by down-regulating the high expression of CTGF in myocardial tissue of diabetic rats,thereby delaying myocardial fibrosis.The results indicate that the therapy of treating both phlegm and blood stasis has better performance than the simple method of resolving phlegm or stasis.

关 键 词：抵当陷胸汤 糖尿病大鼠 心肌细胞 结缔生长因子(CTGF) 低密度脂蛋白受体相关蛋白(LRP) 

分 类 号：R2-0[医药卫生—中医学] R22R285.5R289R33