氯沙坦对糖尿病大鼠肾小球信号蛋白JAK2和STAT3表达的影响  

Effect of losartan on expression of Janus kinase 2 and signal transducer and activator of transcription 3 in glomeruli of diabetic rats

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

机构地区：[1]河北医科大学病理学教研室,石家庄050017

出　　处：《中国危重病急救医学》2005年第11期662-666,共5页Chinese Critical Care Medicine

基　　金：河北省自然科学基金资助项目(C2004000536)

摘　　要：目的探讨血管紧张素1型受体拮抗剂氯沙坦对糖尿病大鼠肾小球信号蛋白Janus酪氨酸蛋白激酶2(JAK2)与信号转导子和转录激活子3(STAT3)表达的影响。方法雄性Wistar大鼠60只,随机分为正常对照组、糖尿病组和氯沙坦治疗组。腹腔注射链脲佐菌素(STZ)诱发糖尿病大鼠模型,每日灌胃氯沙坦10mg/kg。采用蛋白质免疫印迹法(Westernblot)检测肾小球细胞JAK2、STAT3和磷酸化STAT3(pSTAT3)蛋白的表达,免疫沉淀和Westernblot检测磷酸化JAK2(pJAK2)情况,逆转录聚合酶链反应(RTPCR)检测肾小球细胞JAK2和STAT3mRNA的表达。结果在2周和4周时,糖尿病组较对照组肾小球JAK2、pJAK2、STAT3、pSTAT3蛋白及其JAK2和STAT3mRNA表达明显增强(P均<0.01)。氯沙坦治疗组较糖尿病组pJAK2和pSTAT3表达降低(P<0.05)。氯沙坦对JAK2和STAT3蛋白及其mRNA的表达无明显影响。结论JAK2和STAT3信号蛋白可能参与了糖尿病早期肾脏的发病过程,氯沙坦对肾脏保护作用可能部分是通过影响JAK/STAT信号途径的激活而实现的。Objective To investigate the effects of losartan on Janus kinase 2 （JAK2） and signal transducer and activator of transcription 3 in glomeruli of diabetic rats. Methods Sixty Wistar male rats were randomly divided into control group （n = 20）, diabetes group （n = 20）, and losartan treatment group （n=20）. Diabetes was induced by intraperitoneal injection of streptozotocin （STZ, 65 mg/kg）. Losartan （10 mg/kg） was administered daily by gavage from the day following the induction of diabetes. The animals were sacrificed in the weeks 2 and 4 after STZ injection. The renal cortical tissues were obtained and glomeruli were isolated. The protein expressions of JAK2, STAT3 and tryosine phosphorylated STAT3 （p- STAT3） were assessed respectively by Western blot, Immunoprecipitation and Western blot analysis were used to determine tryosine phosphorylated JAK2 （p -JAK2）. JAK2 and STAT3 mRNA were assayed by reverse transcription -polymerase chain reaction （RT -PCR）. Results Compared with the control group rats, the respective expression of JAK2, p -JAK2, STAT3, p -STAT3, JAK2 mRNA and STAT3 mRNA was significantly increased in the diabetic glomeruli without losartan treatment （all P 〈 0.01 ）. After treatment with losartan, the expression of p -JAK2 and p -STAT3 in the diabetic glomeruli was downregulated （all P〈0.05）. However losartan had no effect on the expression of JAK2, STAT3, JAK2 mRNA and STAT3 mRNA in the diabetic glomeruli. Conclusion JAK2 and STAT3 signal proteins may be involved in the kidney damage associated with diabetes. Regulation of phosphorylation of JAK2 and STAT3 may be responsible for the renal protective effects of losartan in diabetic rats.

关 键 词：血管紧张素Ⅱ1型受体拮抗剂 糖尿病肾病 Janus酪氨酸蛋白激酶2 信号转导子和转录激活子3 

分 类 号：R96[医药卫生—药理学]