糖尿病仓鼠肾脏chymase mRNA表达及酶活性与AngⅡ和肾脏病变关系的实验研究  

Relationship of gene expression and activity of chymase and Ang Ⅱ,nephropathy in streptozotocin-induced diabetic hamsters

作　　者：程黎[1] 肖谦[1] 蒲霞[1] 李龙英[2] 赵柯湘[1] 高原[1] 

机构地区：[1]重庆医科大学附属第一医院老年病科,重庆400016 [2]四川省成都市金牛区成都铁路中心医院内分泌科,成都610081

出　　处：《重庆医科大学学报》2009年第8期1011-1014,共4页Journal of Chongqing Medical University

基　　金：重庆市卫生局课题(05-2-194)

摘　　要：目的:探讨糖尿病仓鼠肾脏chymase mRNA表达及酶活性与血管紧张素Ⅱ(AngiotensinⅡ,AngⅡ)水平和肾脏病变的关系。方法:30只8周龄雄性仓鼠随机分为正常对照组(n=10)和糖尿病组(n=20),腹腔内注射链脲菌素制备糖尿病仓鼠模型,电镜观察肾脏超微结构,反转录-聚合酶链反应(RT-PCR)检测chymase mRNA水平,放射免疫分析法测定肾脏chymase、血管紧张素转换酶(Angiotensin-convertion enzyme,ACE)活性和AngⅡ含量。结果:(1)糖尿病组24h尿白蛋白含量高于对照组,(2.32±0.18)mgvs(0.11±0.01)mg,P<0.01,透射电镜发现糖尿病组肾小球毛细血管基底膜增厚,系膜细胞间细胞外基质沉积;(2)与对照组相比,糖尿病组肾脏chymasemRNA表达水平明显增高(4.90±0.79vs1.81±0.09,P<0.01),酶活性也明显增高,(0.82±0.05)Uvs(0.49±0.03)U,P<0.01,AngⅡ含量明显增高,(88.6±17.5)pg/mgvs(48.2±15.3)pg/mg,P<0.01,ACE活性无差异(P>0.05)。结论:糖尿病仓鼠肾脏chymase mRNA表达水平和酶活性明显增高可能是AngⅡ水平升高的主要原因,chymase可能有关于糖尿病肾病(Diabetic nephropathy,DN)的发生。Objective：To investigate the relationship of gene expression and activity of chymase and Ang Ⅱwith nephropathy in the streptozotocin（STZ）-induced diabetic hamsters.Methods：Thirty male hamsters were randomly divided into two groups：normal controls and diabetic rats.Diabetes mellitus was induced in rats by intraperitoneal streptozotocin injection.The nephritic ultrastructure was observed with electron microscope.The levels of blood glucose,lipoprotein were measured by biochemical methods.The level of angiotensin Ⅱ（Ang Ⅱ） and the activity of chymase and angiotensin-convertion enzyme（ACE） were measured by radioimmuno assay.Reverse transcription polymerase chain reaction（RT-PCR）was used to determine chymase gene expression（corrected by β-actin）.Results：Chymase activity in DN group was much higher than that in the control group（0.82±0.05） U vs（0.49±0.03） U,P〈0.01.This was accompanied by increased angiotensin Ⅱ（88.6±17.5） pg/mg tissue vs（48.2±15.3） pg/mg tissue,P〈0.01 and chymase mRNA（1.81±0.09） vs（4.90±0.79）,P〈0.01.But the activity of ACE was unchanged,indicating an alternative non-ACE dependent way of angiotensin Ⅱgenerating.Conclusion：In diabetic hamsters,the gene expression and activity of chymase are much higher than those in the control group,accompanying higher level of angiotensin Ⅱ.This reflects another mechanism was involved except for the classic ACE pathway to activate the intrarenal RAS in the progress of diabetic nephropathy（DN）.

关 键 词：CHYMASE 糖尿病肾病 血管紧张素Ⅱ 

分 类 号：R587.2[医药卫生—内分泌]