阿托伐他汀对糖尿病肾病大鼠肾组织中JAK/STAT信号通路及其抑制因子SOCS-1表达的影响

Effect of Atorvastatin on the JAK/STAT Signaling Pathway and SOCS-1 in Renal Tissue of the Diabetic Nephropathy Rats

目的:观察糖尿病肾病(DN)大鼠肾组织中JAK-STAT-SOCS负反馈调节机制的变化,以期阐明阿托伐他汀对DN炎症发病机制及其防治措施。方法:60只Wistar雄性大鼠随机分成正常对照组(对照组)、DN模型组(模型组)、阿托伐他汀治疗组(治疗组),每组20只,利用单侧肾切除加腹腔注射链脲佐菌素(50mg/kg)建立DN大鼠模型,治疗组每日每只灌胃阿托伐他汀(8mg·kg-1·d-1),正常对照组及模型组每日每只给予等量蒸馏水,连续给药12周。记录大鼠体重;观察尿微量白蛋白(MALB-U)、24h尿蛋白定量(24hUpr)、血肌酐(Scr)、尿素氮(BUN)变化;取肾组织行PAS、HE染色观察病理组织学变化;用免疫组织化学染色方法检测肾组织中p-STAT3,p-JAK2,SOCS-1表达水平的变化。结果:12周末,模型组大鼠MALB-U、24hUpr、Scr、BUN显著升高,与对照组比较(P<0.05);阿托伐他汀治疗后,各指标显著降低,与模型组比较(P<0.05)。12周时模型组大鼠肾组织中p-STAT3、p-JAK2、SOCS-1表达水平升高,与对照组相比差异有统计学意义(P<0.05);经阿托伐他汀治疗12周后,大鼠肾组织SOCS-1表达水平较同期模型组明显上调(P<0.05),而p-STAT3、p-JAK2的表达受到抑制,低于同期模型组(P<0.05)。结论:JAK-STAT-SOCS负反馈调节机制可能参与DN的发病过程;阿托伐他汀可能通过调节肾组织p-STAT3、p-JAK2、SOCS-1的表达,减轻DN大鼠的炎症反应,对肾脏有一定保护作用。

Objective：To investigate the effects of atorvastatin on the JAK-STAT-SOCS regulating mechanism in the diabetic nephropathy rats.Methods：Totally 60 Wistar rats were divided randomly into three groups： normal control （control group）,DN control （model group）,atorvastatin treated group,20 rats in each group.The rat models were induced by right nephrectomy （50 mg/kg） and peritoneal injection of low-dosage streptozotocin.Atorvastatin （8 mg·kg-1·d-1） was administrated by gavage for 12 weeks.Body weight,the microalbuminuria （MALB-U）,the urinary protein quantity in 24h （24 h Upr）,serum creatinine（Scr） and urea nitrogen（BUN） were measured.PAS、HE staining was used to observe morphological changes of renal tissue under light microscope.Expression levels of p-STAT3,p-JAK2,SOCS-1 in renal tissue of rats detected by immunohistochemistry.Results：In 12w,MALB-U,24 h Upr,Scr and BUN of model group rats were higher distinctly than those of control group （respectively,P0.05）.After treatment of atorvastatin,those were reduced distinctly （respectively,P0.05）.Immunohistochemistry staining showed that in model group,the expressions of p-STAT3,p-JAK2,SOCS-1 in 12-week were higher significantly than those in control group （respectively,P0.05）.After treatment of atorvastatin,the expression of SOCS-1 of renal tissue in treatment group was higher significantly compared with model group in the same period （respectively,P0.05）,the expressions of p-STAT3 and p-JAK2 of renal tissue in treatment group were lower compared with those of model group in the same period （respectively,P0.05）.Conclusion：Atorvastatin could reduce glomerular damage in DN,which mechanism may be involved in the in the inhibition of JAK-STAT-SOCS regulating mechanism.