加味四君子汤对阿霉素肾病大鼠FAK/p38MAPK途径的影响  

Effects of Jiawei Sijunzi Decoction on FAK/p38 pathway in the rats with adriamycininduced nephropathy

作　　者：郑京[1] 陈雪兰[1] 吴心虹[2] 刘慈赟[3] 张娟[1] 郑雪敏[3] 林秀芹[3] 陈小英[3] 

机构地区：[1]福建中医药大学附属人民医院,福州350004 [2]厦门大学附属第一医院同民分院,厦门361000 [3]福建中医药大学,福州350100

出　　处：《中华中医药杂志》2014年第10期3270-3274,共5页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：福建省自然科学基金项目(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/p38途径的影响。方法:建立阿霉素肾病综合征大鼠模型,以随机数字表随机分为正常组、模型组、激素组、中药组(加味四君子汤)、中药+激素组,每组10只。测大鼠24h尿蛋白;电镜下进行肾脏超微病理观察,实时荧光定量PCR检测肾组织FAK、p38mRNA表达,Western Blot检测肾皮质FAK、p38蛋白及磷酸化。结果:1第21天,激素组、中药组、中药+激素组尿蛋白均较模型组降低(P<0.05,P<0.01)。第35天,与模型组比较,3组尿蛋白均显著性降低(P<0.01)。第35天与第21天相比,模型组显著性升高、激素组和中药+激素组显著性降低(P<0.05)。2模型组足细胞肿胀,足突增宽、部分或弥漫性融合;各治疗组肾小球病变明显减轻,仅见部分足突融合。3与模型组比较,各药物干预组FAK mRNA、p38 mRNA表达显著性减少(P<0.01)。4模型组FAK总蛋白及FAK、p38磷酸化蛋白显著性增高(P<0.01),与模型组比,各药物干预组FAK总蛋白及FAK、p38磷酸化蛋白显著性降低(P<0.05)。结论:阿霉素可通过FAK/p38途径导致阿霉素肾病的形成;肾组织FAK磷酸化,可诱导下游p38通路激活,介导肾脏损伤;加味四君子汤、激素能抑制FAK/p38通路,降低阿霉素肾病大鼠蛋白尿。Objective： To investigate the treatment effects of Jiawei Sijunzi Decoction on rats with adriamycin-induced nephritic and influence on FAK/p38 MAPK pathway. Methods： The animal models of rats with adriamycin-induced nephropathy were established. The rats were divided into control group, model group, hormone group, Chinese medicine group and hormone plus Chinese medicine group by random number table method. 24-hour urine protein was tested. Real-time fluorescent quantitative PCR was used to test the mRNA expression of FAK and p38-MAPK. Western Blot was used to test the expression of FAK and p38-MAPK protein. Results： 1Compared with the model group, urine protein of rats in hormone group and hormone plus Chinese medicine group was decreased in the 21 st day（P〈0.05, P〈0.01）. Compared with the model group, urine protein of the other 3 groups was decreased significantly in the 35 th day（P〈0.01）. Compared with the 21 st day, the results of urine protein tested in the 35 th day of the model group were increased, and urine protein of hormone group and hormone plus Chinese medicine group was decreased significantly（P〈0.05）. 2In rats of model group, sertoli cells were swelling, foot processes were broadening and dif use fusion. Minor glomerular abnormalities of each treatment group were visibly decreased. 3Compared with model group, FAK and p38 mRNA expression of rats in treatment group were decreased（P〈0.01）. 4Expression of total protein of FAK and phosphorylated protein of FAK and p38 of rats in the model group were increased（P〈0.01）. Compared with the model group, expression of total protein of FAK and phosphorylated protein of FAK and p38 of rats in the treatment group were decreased（P〈0.05）. Conclusion： Adriamycin can lead to the formation of adriamycin nephropathy via the FAK/p38 MAPK pathway. FAK phosphorylation can induce p38 pathway activation to mediated kidney damage. Jiawei Sijunzi Decoction and hormone can decrease the proteinuria of rats with adriamycin nephropath

关 键 词：加味四君子汤 阿霉素肾病 黏着斑激酶 p38丝裂原活化蛋白激酶 

分 类 号：R277.5[医药卫生—中医学]