TGF-β1/p38MAPK通路对肾间质纤维化影响及抗纤灵冲剂干预机制的实验研究  

Experimental study on role of TGF-β1/p38 mitogen-activated protein kinase pathway to renal interstitial fibrosis and intervention mechanisms of Kang Xianling Decoction

作　　者：张新志[1] 黄迪[2] 吴锋[1] 郝俊杰[1] 李会龙[2] 何立群[2] 

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]上海中医药大学附属曙光医院肾内科,上海201203

出　　处：《中华中医药杂志》2011年第2期245-248,共4页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家自然科学基金项目资助(No.30873259);上海市优秀学科带头人培养计划资助(No.08XD14039);上海市教育委员会E-研究院建设计划项目资助(No.E03008);上海市教委高校创新团队(No.201203)~~

摘　　要：目的:探讨TGF-β1/p38丝裂素活化蛋白激酶(p38MAPK)通路对肾间质纤维化的影响及抗纤灵冲剂的干预机制。方法:将120只SD大鼠中72只行经典单侧输尿管结扎,制备单侧输尿管结扎动物模型,造模成功后分为正常组、假手术组、模型组、抗纤灵组,氯沙坦组。药物干预7、14、21、28d后分批处死,留取左侧肾组织,运用Western blotting检测肾组织p38的表达,免疫组化方法测定转化生长因子β1(TGF-β1)的蛋白表达。结果:与同一时间点假手术组比较,模型组p38/β-actin相对表达量及TGF-β1蛋白表达显著升高(P<0.01),抗纤灵组及氯沙坦组此二指标均较模型组明显降低,且抗纤灵组下降更为明显(P<0.05,P<0.01)。结论:抗纤灵冲剂可能是通过调节TGF-β1/P38MAPK信号转导通路,发挥抗肾小管间质纤维化效应。Objective： To investigate the role of TGF-β1/p38 mitogen-activated protein kinase pathway to renal interstitial fibrosis and the intervention mechanisms of Kang Xianling Decoction.Methods： 120 specified-pathogens free SD rats,in which 72 of them were underwent UUO operation,were randomly divided into normal group,sham-operation group,model group,Kang Xianling（KXL） group and Losartan group.After made model and cured for 7,l4,21,28d.The animals were killed in batch to get their nephridial tissue.Applied western blotting to determine the expression of p38MAPK and immunohistochemical method to detect the protein expression of TGF-β1.Results： Compared with sham-operation groups on the same day,the expression of p38/β-actin rised obviously in model group,which were 118.25,265,179.25 and 654 times than the latter.The protein expression of TGF-β1 increased obviously too,which were 6.55,13.79,15.71 and 17.55 times than the sham-operation groups.The expression of Kang Xianling（KXL） group and Losartan group declined significantly,and the former descended more.Coincidentally,the protein expression of TGF-β1 had the same tendency.Conclusion： TGF-β1 and p38 mitogen-activated protein kinase pathway may play an important role in the renal tubulointerstitial fibrosis.Kang Xianling Decoction may bring into full play to resist the renal tubulointerstitial fibrosis through regulating TGF-β1/p38 mitogen-activated protein kinase pathway,interfering in lipid metabolism,lessening proteinuria,improving kidney hemodynamics,improving oxidative stress system and affecting secretion of various kinds of cytokines.

关 键 词：UUO动物模型 P38MAPK通路 TGF-Β1 肾间质纤维化 抗纤灵冲剂 

分 类 号：R285.5[医药卫生—中药学]