雷公藤多苷调节肾组织p38MAPK信号通路改善糖尿病肾病肾小球炎症性损伤的作用和机制  

Effects and mechanisms of multi-glycoside of Tripterygium wilfordii improving glomerular inflammatory injury by regulating p38MAPK signaling activation in diabetic nephropathy rats

作　　者：黄燕如[1,2] 万毅刚[2,3] 孙伟[2] 毛志敏[1,2] 赵青[2] 史喜苗[1,2] 姚建 

机构地区：[1]南京中医药大学中西医结合鼓楼临床医学院,江苏南京210008 [2]南京中医药大学肾病研究所,江苏南京210029 [3]南京大学医学院附属鼓楼医院中医科,江苏南京210008 [4]Department of Molecular Signaling,University of Yamanashi

出　　处：《中国中药杂志》2014年第21期4102-4109,共8页China Journal of Chinese Materia Medica

基　　金：国家自然科学基金面上项目(81374030);南京市卫生青年人才培养工程项目

摘　　要：目的:探讨雷公藤多苷(multi-glycoside of Tripterygium wilfordii,GTW)在体内改善糖尿病肾病(diabetic nephropathy,DN)模型鼠肾小球炎症性损伤的作用和机制。方法:采用单侧肾切除联合腹腔注射链脲佐菌素(streptozotocin,STZ)建立DN模型。将大鼠随机分为3组:假手术组、对照组、GTW组,各5只。大鼠在造模成功后分别经灌胃给予蒸馏水(2 m L)或GTW悬浊液(50 mg·kg-1·d-1),每日1次,连续8周。各组大鼠自给药开始计时,第8周末处死。采集血液、尿液样本和肾组织,观察各组大鼠尿白蛋白、肾功能、肾小球形态特征、巨噬细胞(ED1+细胞)浸润以及肾组织肿瘤坏死因子(tumor necrosis factor,TNF)-α,白介素(interleukin,IL)-1β,p38丝裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK),磷酸化p38MAPK(phosphorylated p38,p-p38MAPK),转化生长因子(transforming growth factor,TGF)-β1的蛋白表达水平。结果:GTW能改善DN模型鼠一般情况、体重,减少尿白蛋白,减轻肾小球硬化,抑制肾小球ED1+细胞浸润,下调肾组织TNF-α,IL-1β,p-p38MAPK,TGF-β1蛋白表达水平。结论:GTW在体内具有抑制炎症细胞浸润和炎症因子表达,减轻肾组织炎症性损伤的作用;GTW通过下调肾组织p38MAPK信号通路中关键信号分子——p-p38MAPK蛋白表达水平,抑制炎症信号通路活性,减少TGF-β1表达,从而,改善肾组织炎症性损伤。Objective： To explore the effects and mechanisms of multi-glycoside of Tripterygium wilfordii（GTW） on improving glomerular inflammatory lesion in rats with diabetic nephropathy（DN）. Method： DN model was induced by unilateral nephrectomy and intraperitoneal injection of STZ（35 mg·kg^-1）twice. The rats were randomly divided into 3 groups, the sham-operated group （Sham group, n = 5 ）, the vehicle-given group （ Vehicle group, n = 5 ） and GTW-treated group （ GTW group, n = 5 ）. After the model was successfully established,the rats in GTW group were daily oral administrated with GTW suspension（50 mg·kg^-1·d^-1）, meanwhile,the rats in Vehicle group were daily oral administrated with distilled water （2 mL） for 8 weeks. From the beginning of the administration, all rats were killed 8 weeks later. Blood and renal tissues were collected, and then UAlb, renal function, glomerular morphology charac- teristics and glomerular macrophages（ ED1^＋ cells）infiltration, as well as the protein expressions of inflammatory cytokines including tumor necrosis factor（TNF）-α and interleukin（IL）-1β, and the key molecules in p38MAPK signaling pathway including p38 mitogenactivated protein kinase （MAPK）, phosphorylated p38 （p-p38 MAPK）and transforming growth factor（TGF）-/31 were investigated respectively. Result： GTW not only ameliorated the general state of health and body weight, but also attenuated UAlb, glomerulosclerosis, the infiltration of glomerular ED1^＋ cells and the protein expressions of TNF-α,IL-β,p-p38MAPK and TGF-β1 in the kidney in DN model rats. Conclusion ： By means of DN model rats, we demonstrated that GTW has the protective effect on renal inflammatory damage in vivo via inhibiting inflammatory cells infiltration and inflammatory cytokines expression. Furthermore, GTW could improve renal inflammatory lesion through down-regulating the expressions of the key signaling molecules in p38MAPK pathway such as p-p38MAPK and TGF-β1 ,and inhibiting the act

关 键 词：糖尿病肾病 雷公藤多苷 炎症 p38丝裂原活化蛋白激酶信号通路 

分 类 号：R259[医药卫生—中西医结合]