益肾解毒汤对5/6肾切除肾间质纤维化模型大鼠肾组织JAK-STAT-SOCS信号途径的影响  

Effects of Yishen Jiedu Tang on the signaling pathway of JAK-STAT-SOCS in renal tissue of rat model with renal interstitial fibrosis after 5/6 subtotal nephrectomy

作　　者：于昊新[1] 方铃[2] 李天舒 费秀丽 刘琨[1] 

机构地区：[1]上海市第六人民医院金山分院肾内科,上海201500 [2]上海市第六人民医院金山分院皮肤科,上海201500 [3]上海市黄浦区妇幼保健所儿保科,上海200010

出　　处：《甘肃中医药大学学报》2017年第3期1-5,共5页Journal of Gansu University of Chinese Medicine

摘　　要：目的研究益肾解毒汤对5/6肾切除肾间质纤维化模型大鼠肾组织Janus激酶-信号传导及转录激活因子-细胞因子信号抑制物(JAK-STAT-SOCS)信号途径的影响,深入探讨益肾解毒汤干预肾间质纤维化、延缓肾脏疾病进展的作用机制。方法将35只雄性SD大鼠随机分为假手术组、模型组、AG490组、益肾解毒汤组4组,每组8只,建立5/6肾切除肾间质纤维化大鼠模型,造模成功后各组给予对应的药物或生理盐水,1月为1个疗程,共治疗3个疗程。末次给药后腹主动脉取血,测定血清肌酐(Scr)、尿素氮(BUN)的含量;处死大鼠,取大鼠肾组织,一部分以多聚甲醛固定后行Masson染色,观察肾组织病理学改变,另一部分采用免疫印迹法检测P-JAK2,P-STAT3,SOCS3蛋白的表达水平。结果与假手术组比较,模型组肾间质纤维化程度明显加重,血清BUN,Scr含量及肾组织P-JAK2,P-STAT3蛋白表达水平明显升高,SOCS3蛋白表达水平明显降低,差异均有统计学意义(P<0.01);与模型组比较,AG490组及益肾解毒汤组肾间质纤维化程度明显减轻,血清BUN,Scr含量及肾组织P-JAK2,P-STAT3蛋白表达水平明显降低,SOCS3蛋白表达水平明显升高,差异均有统计学意义(P<0.05或P<0.01),且益肾解毒汤组的作用显著优于AG490组,差异均有统计学意义(P<0.05或P<0.01)。结论益肾解毒汤是有效抑制肾间质纤维化的中药制剂,可以增强JAKSTAT-SOCS信号途径的负反馈调节,降低JAK通路的磷酸化,从而抑制免疫炎症反应,减轻肾纤维化。Objective To observe the effects of Yishen Jiedu Tang on the signaling pathway of JAK （Janus Kinase）-STAT （signal transducers and activators of transcription）-SOCS （suppressor of cytokine signaling） in renal tissue of rat model with renal interstitial fibrosis after 5/6 subtotal nephrectomy and make a further probe of the de- coction＇ s mechanism in treating renal interstitial fibrosis and slowing the progression of kidney diseases. Methods 35 SD male rats were randomly divided into 4 groups ： sham-operation group, model group, AG490 group and de- coction treatment group ,8 rats of each. Rat models with renal interstitial fibrosis were established and then were in- tervened with corresponding drugs or saline, one month as a course and 3 courses as a whole. After treatment, Scr （serum creatinine） and BUN （urea nitrogen） were detected;one part of renal tissues were fixed in paraformalde- hyde and given Masson staining to observe the pathological changes ; another part were intervened with Western blot- ting to test the expression of the P-JAK2,P-STAT3 and SOCS3. Results Compared with those in sham-operation group, renal interstitial fibrosis in model group became severe, content of BUN, Ser and the expression of P-JAK2 and P-STAT3 increased while SOCS3 decreased,the difference was significant （P〈0.01）. Compared with model group, renal interstitial fibrosis was relieved in AG490 group and decoction treatment group ; content of BUN, Scr and the expression of P-JAK2 and P-STAT3 decreased while SOCS3 increased,the difference was also significant （P〈 0.05 or P〈0.01 ）. The effect in decoction treatment group was visibly superior to that in AG490 group,there was a statistical significance （P〈0.05 or P〈0.01 ）. Conclusion Yishen Jiedu Tang is effective in inhibiting renal inter- stitial fibrosis. It can enhance the negative feedback mechanism, reduce the phosphorylation of JAK pathway, and so get the effect of immune inflammation suppression and renal fibrosis relief.

关 键 词：肾间质纤维化 益肾解毒汤 5/6肾切除 大鼠 Janus激酶-信号传导及转录激活因子-细胞因子信号抑制物信号途径 血肌酐 尿素氮 实验研究 

分 类 号：R285.5[医药卫生—中药学]