厄贝沙坦对糖尿病大鼠肾脏FN、DKK1及β-catenin表达的影响  

Influence of irbesartan on expression of fibronectin,Dickkopf-1,and β-catenin in kidney of diabetic rats

作　　者：陈碧珊[1] 吴红卫[1] 李艳 张滨[1] 陈吉生[1] CHEN Bishan;WU Hongwei;LI Yan;ZHANG Bin;CHEN Jisheng(The First Affiliated Hospital of Guangdong Pharmaceutical University,Guangzhou 510080,China)

机构地区：[1]广东药科大学附属第一医院,广州510080

出　　处：《山东医药》2018年第32期47-50,共4页Shandong Medical Journal

基　　金：国家自然科学基金资助项目(81603526)

摘　　要：目的探讨厄贝沙坦对糖尿病肾损伤的治疗作用及其机制。方法取SD大鼠32只,随机选取10只设为正常组,余22只建立链脲佐菌素糖尿病大鼠模型。其中20只建模成功,随机均分为不进行治疗的模型组和应用厄贝沙坦治疗的厄贝沙坦组,干预12周。检测各组肾质量/体质量、血尿素氮(BUN)及尿白蛋白/肌酐(UACR);采用免疫组化法检测大鼠肾组织纤维连接蛋白(FN)、Dickkopf-1(DKK1)及β-连环蛋白(β-catenin)表达(以染色阳性区域面积/整个肾小球面积表示),采用实时荧光定量PCR法检测FN、DKK1、β-catenin mRNA表达。分析糖尿病大鼠肾组织DKK1 mRNA表达与UACR、FN mRNA表达的关系。结果模型组、厄贝沙坦组、正常组肾质量/体质量分别为(4.7±0.6)%、(3.8±0.5)%、(3.2±0.4)%,三组间比较P均<0.05。模型组、厄贝沙坦组血BUN及UACR均高于正常组,厄贝沙坦组均低于模型组(P均<0.05)。模型组、厄贝沙坦肾组织FN、DKK1蛋白表达均高于正常组,β-catenin蛋白表达均低于正常组(P均<0.05);厄贝沙坦组肾组织FN、DKK1蛋白表达均低于模型组,β-catenin蛋白表达均高于模型组(P均<0.05)。模型组、厄贝沙坦组肾组织FN、DKK1 mRNA相对表达量均高于正常组,厄贝沙坦组均低于模型组(P均<0.05);三组肾组织β-catenin mRNA相对表达量比较差异均无统计学意义(P均>0.05)。糖尿病大鼠肾组织DKK1 mRNA表达与UACR、FN mRNA表达均呈正相关(r分别为0.796、0.751,P均<0.05)。结论厄贝沙坦可减缓糖尿病大鼠肾损伤的发生发展,其机制可能为抑制肾组织FN、DKK1表达,促进β-catenin表达。。Objective To explore the influence of irbesartan on expression of fibronectin(FN),Dickkopf-1(DKK1),andβ-catenin in kidney of diabetic rats.Methods Thirty-two SD rats were selected,10 were randomly selected as the normal group,and the remaining 22 were set up as the model of streptozotocin(STZ)diabetic SD rats.Twenty of them were successfully modeled and randomly divided into the untreated model group and the irbesartan group treated with erbesartan,and they were treated for 12 weeks.The renal mass/body mass,urea nitrogen(BUN)and albumin/creatinine(UACR)were tested.The expression of rat renal tissue fibronectin(FN),Dickkopf-1(DKK1)andβ-catenin was tested by immunohistochemistry,and the expression of FN,DKK1,β-catenin mRNA was tested by real-time fluorescent quantitative PCR.The relationship of DKK1 mRNA with UACR,FN mRNA was analyzed.Results The renal mass/body mass:the model group was 4.7%±0.6%,the irbesartan group was 3.8%±0.5%,and the normal group was 3.2%±0.4%(P<0.05).The BUN and UACR were higher in the model group and the irbesartan group than in the normal group(both P<0.05),the BUN and UACR were lower in the irbesartan group than in the model group(both P<0.05).The FN and DKK1 for the model group and the irbesartan group were higher than those in the normal group(both P<0.05),theβ-catenin was lower in the model group and the irbesartan group than in the normal group(P<0.05),the FN and DKK1 for the irbesartan group were lower than those in the model group(both P<0.05),and theβ-catenin in the irbesartan group was higher than that in the model group(P<0.05).The FN and DKK1 mRNA were higher in the model group and the irbesartan group than in the normal group(P<0.05),and the FN and DKK1 mRNA were lower in the irbesartan group than in the model group(P<0.05).There was no significant difference on theβ-catenin mRNA between the three groups(P>0.05).The expression of DKK1 mRNA was positively correlated with the expression of UACR and FN mRNA(r=0.796,0.751;both P<0.05).Conclusion Irbesartan can slow do

关 键 词：糖尿病 糖尿病肾病 厄贝沙坦 纤维连接蛋白 DICKKOPF-1 Β-连环蛋白 大鼠 

分 类 号：R587.1[医药卫生—内分泌]