白芍总苷对糖尿病所致心肌损伤的保护作用及机制研究  

Protective mechanism of total glucosides of paeony on myocardial injury induced by diabetes mellitus

作　　者：王振贤[1] 王立哲[2] WANG Zhenxian;WANG Lizhe(First Department of Endocrinology,Handan Central Hospital,Handan 056001,China)

机构地区：[1]邯郸市中心医院内分泌一科,056001 [2]邯郸市中心医院康复医学科,056001

出　　处：《浙江医学》2021年第21期2294-2298,I0005,共6页Zhejiang Medical Journal

基　　金：邯郸市科学技术研究与发展计划项目(1823208094ZC)。

摘　　要：目的探讨白芍总苷(TGP)对糖尿病所致心肌损伤的保护作用及机制。方法取120只SD大鼠按随机数字表法分为二甲双胍(Met)组、TGP低、中、高剂量组、模型组和正常对照组6组,每组20只;采用一次性腹腔注射链尿佐菌素联合高脂饲料喂养的方法制备糖尿病心肌病大鼠模型;自造模第1天开始,Met组1次/d 40 mg/ml的Met溶液灌胃,TGP低、中、高剂量组分别1次/d 10、20、40 mg/ml的TGP溶液灌胃,模型组和正常对照组1次/d 0.9%氯化钠溶液灌胃,溶液体积均为5 ml/kg,疗程8周。8周后采用血糖仪检测FPG水平,动物超声仪检测心功能指标,HE染色、Masson染色观察心肌组织病理学改变和纤维化程度,ELISA法检测血清炎症因子含量,Western blot法检测心肌组织Toll样受体4(TLR4)、髓样分化蛋白(MyD88)、NF-κB蛋白表达水平。结果与正常对照组比较,模型组大鼠FPG水平明显升高(P<0.01);与模型组比较,Met组和TGP中、高剂量组FPG水平均明显降低(均P<0.01)。与正常对照组比较,模型组大鼠左心室舒张末期内径(LVIDd)、左心室收缩末期内径(LVIDs)均明显升高,而射血分数(EF)、每搏输出量(SV)均明显降低(均P<0.01);与模型组比较,Met组和TGP中、高剂量组LVIDd、LVIDs均明显降低,而EF、SV均明显升高(均P<0.05);与Met组比较,TGP高剂量组LVIDs明显降低,EF、SV均明显升高(均P<0.05)。正常对照组大鼠心肌纤维排列整齐规则,细胞形态正常、结构完整,着色均匀;模型组可见心肌纤维断裂、排列紊乱,细胞呈空泡变性,可见大量炎性细胞浸润;与模型组比较,Met组和TGP低、中、高剂量组心肌纤维和细胞病变呈不同程度改善,其中TGP高剂量组未见心肌纤维断裂,炎性细胞浸润数量明显减少。正常对照组大鼠心肌可见肌束平行方向的胶原纤维,含量事宜、分布均匀;与正常对照组比较,模型组蓝染胶原纤维明显增多,排列紊乱,分布不均、以血管周围含量较多;Objective To investigate the protective effect and mechanism of total glucosides of paeony(TGP)on myocardial structure and function in diabetic rats.Methods A total of 120 SD rats were randomly divided into normal control group,model group,metformin(Met)group and low-,medium-and high-dose TGP groups,with 20 rats in each group.The diabetic cardiomyopathy rat model was prepared by intraperitoneal injection of streptozotocin combined with high-fat feed.From the first day of modeling,the Met group was intragastrically administered with a concentration Met solution(40 ml/kg,volume 5 ml/kg)q.d,the low-,medium-and high-dose TGP groups were intragastrically administered with TGP solution 10,20 or 40 ml/kg(volume 5 ml/kg)q.d,respectively,the model group and normal control group were intragastrically administered with 0.9%sodium chloride solution(volume 5 ml/kg),the course of treatment was 8 weeks.The FPG level was detected by blood glucose meter,cardiac function indexes were detected by animal ultrasound system,myocardial pathological changes and fibrosis degree were observed by HE staining and Masson staining,the serum inflammatory factor levels were detected by ELISA,and the expression of toll-like receptor 4(TLR4),myeloid differentiation factor 88(MyD88),NF-κB protein in myocardial tissue was detected by Western blot.Results Compared with the normal control group,the FPG level of rats in the model group was significantly increased(P<0.01),the left ventricular end-diastolic diameter(LVIDd),left ventricular end-systolic left ventricular diameter(LVIDs)were significantly increased and the ejection fraction(EF),stroke volume(SV)were significantly decreased(P<0.01),in myocardial tissue,myocardial fibers were broken and arranged disorderly,the cells presented vacuolar degeneration and a large number of inflammatory cell infiltration,blue-stained collagen fibers were significantly increased,arranged disorderly,and unevenly distributed with more content around blood vessels,the contents of TNF-α,IL-1β,IL-6 in serum were sig

关 键 词：白芍总苷 糖尿病 心肌损伤 炎症 Toll样受体4/髓样分化蛋白/核因子-κB通路 

分 类 号：R285.5[医药卫生—中药学]