雷帕霉素抑制IgA肾病大鼠肾小球信号蛋白STAT3的活化  

Rapamycin inhibits activation of STAT3 in renal tissue of IgA nephropathy rats

作　　者：戎赞华[1] 段惠军[1] 郝军[1] 王晨[1] 史永红[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：《基础医学与临床》2008年第5期460-464,共5页Basic and Clinical Medicine

基　　金：河北省自然科学基金(C2006000825)

摘　　要：目的探讨雷帕霉素对IgA肾病大鼠肾组织p-JAK2、STAT3、p-STAT3和PCNA表达的影响。方法制备IgA肾病动物模型,分为对照组、IgA肾病组、氯沙坦(ls)和雷帕霉素(rapa)治疗组。监测大鼠的生化指标及用免疫组化、Western blot、RT-PCR等方法检测肾组织p-JAK2、STAT3、p-STAT3和PCNA的蛋白及mRNA的表达。结果IgA肾病大鼠较对照组24 h尿蛋白定量明显升高、血白蛋白降低、BUN以及Cr水平明显升高(P<0.01);IgA肾病大鼠p-JAK2、STAT3、p-STAT3和PCNA蛋白及mRNA水平也显著高于对照组;雷帕霉素能显著缓解上述改变(P<0.01)。结论雷帕霉素可能通过抑制IgA肾病大鼠肾小球JAK/STAT信号途径、直接抑制STAT3的活化以及抑制系膜细胞的增殖而减轻病变程度。Objective To investigate the effects of rapamycin on p-JAK2, STAT3, p-STAT3 and PCNA in ranal tissue of IgAN rats. Methods The animal models of IgA nephropathy were devided into control group, IgAN model group, losartan group and rapamycin group. The clinical efficacy of rapamycin, and its influences on the protein and mRNA expressions of STAT3 ,p-STAT3, p-JAK2 and PCNA were determined by western blot, RT-PCR and immunohistochemical techniques respectively. Results The protein and mRNA expressions of p-STAT3, STAT3, p-JAK2 and PCNA were significantly increased in kidney of IgAN rats（P 〈0. 01 ） ; Rapamycin down-regulated these excessive expressions （P 〈0. 01 ）. Conclusion Rapamycin may extenuate the pathological damage of IgAN rats by inhibiting JAK/STAT signaling pathway, activation of STAT3 and mesangial proliferation.

关 键 词：雷帕霉素 IGA肾病大鼠 p-JAK2 STAT3 P-STAT3 

分 类 号：R692.3[医药卫生—泌尿科学]