灵芝多糖联合二甲双胍对糖尿病大鼠心肌纤维化的干预  

Intervention of Ganoderma lucidum polysaccharide in combination with metformin on myocardial fibrosis in diabetes mellitus rats

作　　者：乔进[1] 施忠[1] 窦志华[1] 徐济良[2] 吴锋[2] 孟国梁[2] 陈惠[3] 郑惠华[3] 

机构地区：[1]南通市第三人民医院药剂科,江苏南通226001 [2]南通大学医学院药理学系,江苏南通226001 [3]江苏安惠生物科技有限公司,江苏南通226006

出　　处：《中国医院药学杂志》2014年第20期1709-1713,共5页Chinese Journal of Hospital Pharmacy

基　　金：科技部十一五国家科技支撑计划子课题项目(编号:2006DAI06A20-02)

摘　　要：目的:研究灵芝多糖联合二甲双胍对2型糖尿病大鼠心肌纤维化的保护作用。方法:SD大鼠高脂饮食喂养4周后,腹腔注射小剂量链脲佐菌素(STZ)30 mg·kg-1建立2型糖尿病(Type 2 Diabetes Mellitus,T2DM)模型。成模后,将大鼠随机分为模型组、灵芝多糖组(灵芝多糖600 mg·kg-1)、二甲双胍组(二甲双胍600 mg·kg-1)及联合用药组(灵芝多糖300 mg·kg-1+二甲双胍300 mg·kg-1),另设正常对照组。给药治疗12周后观察大鼠一般情况;测量大鼠空腹血糖;测定大鼠心肌过氧化氢酶(CAT)、谷胱甘肽过氧化物酶(GSH-Px)含量;碱水解法测定大鼠心肌羟脯氨酸含量;电镜观察心肌细胞超微结构的变化;蛋白印迹检测心肌组织结缔组织生长因子(CTGF)蛋白表达。结果:联合用药可显著降低大鼠空腹血糖及升高心肌CAT、GSHPx水平,使其心肌组织羟脯氨酸含量下降,减少心肌组织CTGF的表达,减轻心肌纤维化的病理进程。结论:灵芝多糖联合二甲双胍能有效对抗糖尿病大鼠的心肌纤维化,且同等剂量情况下联合用药效果优于单独用药,其机制可能与联合用药增强机体内抗氧化酶的活性、抑制心肌CTGF的表达来有关。OBJECTIVE To study the protective effect of Ganoderma lucidum polysaccharides combined with metformin on myocardial fibrosis in type 2 diabetic rats.METHODS SD rats were fed with high fat diet for 4 weeks,and then were injected with streptozotocin（30 mg·kg^-1） to replicate type 2 diabetic model.The diabetic rats were randomly into normal control group,diabetes group,Ganoderma lucidum polysaccharides group（600 mg·kg^-1）,metformin group（600 mg·kg^-1）,combination group（Ganoderma lucidum polysaccharides 300 mg·kg^-1＋ metformin 300 mg·kg^-1）.After 12 weeks＇ treatment,observing the general state of health of rats,the levels of fasting serum glucose were determined;the activity of CAT and GSH-Px in myocardium was detected,the content of myocardial hydroxyproline was acquired by the method of alkaline hydrolysis.The pathological changes of myocardial cell were examined by electron microscope,and Western blotting method was used to detect myocardial tissue CTGF protein expression.RESULTS Combination group could lower fasting serum glucose significantly,improve the activity of CAT and GSH-Px in myocardium,down-regulate the hydroxyproline in myocardium,reduce the expression of CTGF in myocardium,relieve patho-proceeding of myocardial fibrosis.CONCLUSION Ganoderma lucidum polysaccharides combined with metformin could prevent myocardial fibrosis efficiently,and the effect was better than administering solitarily while the common dosage was the same.The possible mechanism may be related to strengthen the activity of antioxidase in vivo and down regulation of CTGF of myocardium.

关 键 词：灵芝多糖 二甲双胍 糖尿病大鼠 心肌纤维化 结缔组织生长因子 联合用药 

分 类 号：R285.5[医药卫生—中药学]