摘要
目的探讨心肝宝胶囊对链尿佐菌素(streptozocin,STZ)诱导的糖尿病(diabetes mellitus,DM)大鼠早期肾损伤的保护作用及其机制。方法选取24只雄性Wistar大鼠建立STZ DM动物模型。造模后随机分为模型组、心肝宝胶囊治疗组[中药组,0.5g/(kg·d)]及贝那普利治疗组[西药组,4mg/(kg·d)],每组8只,另选取8只大鼠作为空白对照组(空白组)。模型组与空白组给予等量自来水灌胃,连续干预8周。干预4、8周末检测各组大鼠血糖,8周后观察24h尿蛋白(24h urine protein,24hUP)、血尿素氮(blood urea nitrogen,BUN)和肌酐(serum creatinine,SCr),采用免疫组化法检测转化生长因子-β1(transforming growth factor-beta1,TGF-β1)、层黏连蛋白(laminin,LN)、Ⅳ型胶原蛋白(collagenⅣ,Col-Ⅳ)的表达,采用RT-PCR法检测肾脏TGF-β1、组织金属蛋白酶抑制剂-1(tissue inhibitor of matrix metalloproteinase-1,TIMP-1)及纤溶酶原激活物抑制剂(plasminogen activator inhibitor-1,PAI-1)mRNA的表达,行HE、PAS和Masson染色观察肾脏病理变化。结果与空白组比较,DM大鼠造模后出现血糖升高、多饮、多食、多尿、体重减轻、消瘦、体毛枯燥无光泽、易激惹等表现,干预8周后两个用药组症状减轻。与空白组比较,模型组24hUP、SCr、血糖、Col-Ⅳ、LN、TGF-β1阳性表达量,TGF-β1、TIMP-1及PAI-1mRNA,肾小球面积(GA)、细胞外基质(ECM)及ECM/GA均升高,差异均有统计学意义(P<0.01),病理改变可见明显肾小球体积增大,毛细血管袢扩张,小球系膜细胞增生,系膜区基质增多,增宽,基底膜增厚,肾小管排列紊乱,部分上皮细胞可见空泡变性、脱落,可见蛋白管型,间质有炎性细胞浸润。与模型组比较,两个用药组各指标均降低,差异均有统计学意义(P<0.01),病理改变较轻,系膜细胞轻度增生,系膜基质轻度增多。中药组SCr、PAI-1mRNA表达低于西药组(P<0.05),两个用药组其他指标比较,差异无统计意义(P>0.05)。结论心肝宝胶
Objective To discuss the protective effects of Xin＇ganbao Capsule（XC） on early kidney injury in streptozocin（STZ）-induced diabetic rats and its mechanisms.Methods Twenty-four male Wistar rats were selected to establish STZ induced diabetes mellitus（DM） model.After modeling they were randomly divided into the model group,the XC group（at the daily dose of 0.5 g/kg）,and the benazepril group（at the daily dose of 4 mg/kg）,8 in each group.Another 8 rats were chosen as the blank control group.Rats in the model group and the blank control group were administered with equal volume of normal saline by gastrogavage for 8 successive weeks.The blood glucose was monitored by the end of the 4th week and the 8th week.The 24 h urine protein（24 hUP）,blood urea nitrogen（BUN）,and serum creatinine（SCr） were detected by the end of the 8th week.The transforming growth factor-beta1（TGF-β1）,laminin（LN）,collagen Ⅳ（Col-Ⅳ） expression were detected using immunohistochemical assay.The mRNA expressions of renal TGF-β1,tissue inhibitor of matrix metalloproteinase-1（TIMP-1）,and plasminogen activator inhibitor-1（PAI-1） were detected using RT-PCR.The pathological changes of the renal tissue were observed by HE,PAS,and Masson stain methods.Results Compared with the blank control group,hyperglycemia,polydipsia,polyphagia,polyuria,weight loss,emaciation,dry and dim body hair,and irritability appeared in the diabetic rats.After 8 weeks the symptoms of the two medication groups were attenuated.When compared with the blank control group,the 24 hUP,SCr,blood glucose,Col-Ⅳ,LN,TGF-β1 positive expression ratio,the levels of TGF-β1,TIMP-1,PAI-1 mRNA,the area of glomerular（GA）,extracellular matrix（ECM）,and ECM/GA all increased in the model group with statistical difference（P0.01）.The pathological changes showed obvious glomerular enlargement,the capillary loop expansion,the proliferation of the mesangial cells,increased mesangial matrix,widen and thicken glomerular basement membrane�
出处
《中国中西医结合杂志》
CAS
CSCD
北大核心
2012年第4期530-536,共7页
Chinese Journal of Integrated Traditional and Western Medicine
基金
国家科技支撑计划项目(No.2007BAI04B10)
