氯沙坦对糖尿病大鼠肾小球信号转导和转录活化因子1表达的影响  

Effects of losartan on the expression of STAT1 in glomeruli of diabetic rats

作　　者：史永红[1] 段惠军[1] 王丽晖[1] 何宁[1] 刘青娟[1] 

机构地区：[1]河北医科大学病理学教研室,河北石家庄050017

出　　处：《中国药理学通报》2005年第3期323-326,共4页Chinese Pharmacological Bulletin

基　　金：河北省自然科学基金资助项目(NoC2004000536)

摘　　要：目的探讨糖尿病大鼠肾小球细胞中信号转导和转录活化因子1磷酸化水平及其mRNA水平的改变以及血管紧张素受体1拮抗剂(AT1Ra)氯沙坦的影响。方法♂Wistar大鼠随机分为对照组、糖尿病组和氯沙坦治疗组,腹腔注射STZ诱发糖尿病大鼠模型,每日灌胃给予氯沙坦40mg·kg-1,共2wk。采用免疫组化和Western印迹检测肾小球细胞磷酸化STAT1(pSTAT1)蛋白的表达,RTPCR检测肾小球细胞STAT1mRNA的表达。结果糖尿病组肾小球p-STAT1表达明显高于对照组(P<001),约是对照组的3倍;氯沙坦治疗组大鼠肾小球pSTAT1的表达明显低于糖尿病组(P<005);RTPCR结果表明糖尿病组肾小球细胞STAT1mRNA表达明显上调,约为对照组的34倍;氯沙坦治疗组STAT1mRNA表达与糖尿病组相比无明显差异。结论STAT1信号途径可能参与了糖尿病早期肾脏的发病过程,氯沙坦的肾脏保护作用可能部分是通过影响STAT1的激活而实现。Aim To investigate the effects of losartan on activation of signal transducers and activators of transcription 1(STAT1) protein and the expression of STAT1 mRNA in glumeruli of diabetic rats.Methods Wistar male rats were randomly divided into three groups: control group, diabetes group and treatment group.Diabetes was induced by intraperitoneal injection of STZ (65 mg·kg^-1 ). Losartan (40 mg·kg^-1 ) was administered daily by gavage from the next day of the induction to diabetes for 2 weeks. The protein expression of p-STAT1 in glomeruli was observed by immunohistochemistry and western blot. STAT1 mRNA was measured by reverse transcription and polymerase chain reaction (RT-PCR).Results Compared with the control group rats, the expression of p-STAT1 was significantly increased in glomeruli in the diabetic rats (P<0.01). After treatment with losartan, the expression of p-STAT1 was decreased (P<0.05). The expression of STAT1 mRNA was significantly elevated in glomeruli in diabetic group rats. However losartan had no effect on the expression of STAT1 mRNA.Conclusion STAT1 signal pathway may be involved in the kidney damage associated with diabetes.Regulation of phosphorylation of STAT1 may be responsible for the renal protective effects of losartan in diabetic rats.

关 键 词：血管紧张素受体1拮抗剂 糖尿病肾病 信号转导和转录活化因子1 

分 类 号：R-332[医药卫生] R322.61