加味四君子汤对阿霉素肾病大鼠FAK的影响  

Effects of Jiawei Sijunzi Decoction on FAK in the podocytes of rats with adriamycin-induced nephrosis

作　　者：吴心虹[1] 郑京[2] 黄璐[1] 陈彩凤[1] 郑雪敏[1] 刘慈云 林秀芹[1] 陈小英[1] 

机构地区：[1]福建中医药大学,福建福州350100 [2]福建中医药大学附属人民医院,福建福州350004

出　　处：《时珍国医国药》2014年第2期302-305,共4页Lishizhen Medicine and Materia Medica Research

基　　金：福建省自然科学基金(No.2012J01378)

摘　　要：目的探讨加味四君子汤对阿霉素肾病大鼠的治疗作用及对FAK的影响。方法建立阿霉素肾病大鼠模型,以加味四君子汤与强的松对照治疗,7d、21d、35 d测大鼠24 h尿蛋白定性;21 d、35 d取血取肾,检测大鼠血生化指标,观察肾组织病理改变,实时荧光定量PCR检测nephrin、desmin、FAK表达水平的变化,Western blot检测肾组织FAK、蛋白及磷酸化,免疫组化检测nephrin蛋白水平。结果①模型组大鼠出现蛋白尿,足突广泛融合,中药组较模型组改善。②模型组大鼠较正常组nephrin mRNA表达降低,FAK、desmin mRNA表达升高,药物干预后nephrin表达升高,FAK、desmin表达明显降低。③模型组nephrin蛋白表达明显减少,各治疗组较模型组nephrin蛋白水平明显升高。④模型组FAK总蛋白及磷酸化蛋白增高,P<0.01,各治疗组FAK总蛋白及磷酸化蛋白较模型组降低,P<0.05。结论提示肾组织FAK表达增多及其磷酸化可能是产生大量蛋白尿的重要因素,加味四君子汤、泼尼松能抑制FAK活化,有效降低尿蛋白,上调阿霉素肾病大鼠nephrin表达和分布,同时抑制desmin的表达,对受损肾小球足细胞起到一定保护作用。Objective To investigate the repair effects of Jiawei Sijunzi Decoction on adriamycin - induced nephritic rats and effects on FAK. Methods The rats models were induced by adriamycin to cause nephritic syndrome. Then, the rats were divided into four groups. The first group was the model without any treatment. The second group was treated with Jiawei Sijnnzi Decoc- tion. The third group was treated with prednisone. And the forth group was treated with Jiawei Sijunzi Decoction and prednisone. The quantitation of proteinuria was tested at 7th,21 th and 35th day respectively. Blood and kidney samples were collected at the 21th and 35th day. Histology of kidney was tested by transmission electron microscope. The expression levels of nephrin,podocin and desmin mRNA were tested by RT - PCR. The nephrin protein levels were tested by immunohistochemistry. The expression lev- el of FAK and phosphorylated FAK - Tyr397 were detected by western blot. Results ①Model induced by adriamycin showed an increased proteinuria after 7 days an it lasted to the end. The group treated with Jiawei Sijunzi Decoction has significant differences compared with the model. ②Nephrin mRNA expression in model group was lower than normal group, while desmin and FAK mR- NA expression was higher than normal group. Nephrin mRNA expression in the treatment groups were higher than normal group, while desmin and FAK mRNA expression was lower than model group. ③The nephrin protein level in the model group was lower than normal group obviously at the 21th and 35th day. And the levels in treatment groups were higher than that in model group obviously. ④FAK total protein and phosphorylated proteins in model group were higher than normal group（ P 〈 0. 01 ）. And adriamycin injection helps FAK activation. The protein level of treatment groups was lower than that of model group. Furthermore, the groups treated with Jiawei Sijunzi Decoction and prednisone inhibit FAK activation. Conclusion This experiment suggests that Ad- riamycin injection via the

关 键 词：加味四君子汤 阿霉素肾病 黏着斑激酶 NEPHRIN DESMIN 

分 类 号：R285.5[医药卫生—中药学]