糖尿病肾病大鼠肾组织中TSP-1、TGF-β、APP、VEGF、ColⅠ的表达及意义  

Expression and significance of TSP-1,TGF-β,APP,VEGF and Col Ⅰ in renal tissues of DKD rats

作　　者：冯英[1] 胡昭[2] 张佼佼[1] 

机构地区：[1]天津泰达医院,天津300457 [2]山东大学齐鲁医院

出　　处：《山东医药》2013年第28期5-8,112,共5页Shandong Medical Journal

基　　金：国家科技支撑计划项目(2007BAI04B10)

摘　　要：目的观察糖尿病肾病(DKD)大鼠肾组织中血小板反应因子1(TSP-1)、转化生长因子β(TGF-β)、氨基肽酶P(APP)、血管内皮生长因子(VEGF)、胶原Ⅰ(ColⅠ)的表达,并探讨其临床意义。方法将18只Wistar大鼠随机分为对照组、模型组、治疗组各6只,模型组和治疗组大鼠尾静脉注射链脲佐菌素诱导DKD,造模成功后治疗组给予10 mg/(kg.d)依那普利灌胃,模型组仅予等量缓冲液灌胃;对照组仅尾静脉注射等量缓冲液。给药后20周检测各组大鼠血糖、MAP、24 h尿蛋白、肾质量/体质量,并留取肾组织进行石蜡切片及免疫组化染色,对肾组织中TSP-1、TGF-β、APP、VEGF、ColⅠ的表达进行半定量及相关性分析。结果①与对照组、治疗组比较,模型组大鼠肾间质TSP-1、肾小管TGF-β及肾间质ColⅠ表达均上调(P均<0.01),三者间表达量呈正相关(P均<0.01)。②与对照组比较,模型组大鼠肾间质APP表达下调(P<0.01),且与TSP-1、Col I表达量呈负相关(P均<0.01);肾小管VEGF表达上调(P<0.01),表达量与APP呈负相关(P<0.01),与TGF-β呈正相关(P<0.01)。③模型组大鼠肾小球VEGF、TGF-β表达均高于对照组和治疗组(P均<0.01)。结论 TSP-1-TGF-β轴表达增强,及与TSP-1相关的肾小管周围毛细血管丢失,均可能参与DKD肾间质纤维化。未观察到依那普利对DKD大鼠模型微血管病变有明显抑制作用。Objective To observe the expression and significance of thrombospondin-1（TSP-1）,transforming growth factor-β（TGF-β）,aminopeptidase P（APP）,vascular endothelial growth factor（VEGF） and typeⅠcollagen（ColⅠ） in the renal tissues of rats with diabetic kidney disease（DKD）.Methods Eighteen Wistar rats were randomly divided into three groups,6 in each： the control group,model group and treatment group.Rats in the model and treatment groups were induced to DKD with intravenous injection of strepto zotocin;after the success of modeling,the treatment group was given enalapril 10 mg /（kg.d） intragastric administration and the model group was treated with an equal volume of buffer solution orally;the control group was treated with intravenous injection of equal volume of buffer solution.Twenty weeks later,plasma glucose concentration,MAP,24 h urinary protein excretion and kidney weight / body weight were detected.Then the rats were sacrificed to obtain the kidney tissue,and the kidney tissue sections were stained by immunohistochemistry.The expression of TSP-1,TGF-β,APP,VEGF and ColⅠwas conducted by semi-quantitative and correlation analysis.Results ① Compared with the control group and treatment group,the expression of the interstitial TSP-1,tubular TGF-β and interstitial ColⅠwere all up-regulated in the model group（all P 0.01）.There were significant positive correlations among them（all P 0.01）.② Compared with the control group,the expression of interstitial APP in the model group was down-regulated（P 0.01）,and it showed significantly negative correlations with the expression of interstitial TSP-1 and Col I（all P 0.01）.The expression of tubular VEGF was up-regulated in the model group（P 0.01）,and it showed a positive correlation with TGF-β（P 0.01） and a negative correlation with APP（P 0.01）.③ The expression of glomerular VEGF and TGF-β in the model group was higher than those in the control group and treatment group（all P 0.01）.Conclusions The i

关 键 词：糖尿病肾病 血小板反应因子1 转化生长因子Β 氨基肽酶P 血管内皮生长因子 胶原Ⅰ 

分 类 号：R587.2[医药卫生—内分泌]