黄葵胶囊对阿霉素肾病肾组织炎症信号通路p38MAPK的干预作用  

Effects of Huangkui capsule on renal inflammatory injury by intervening p38MAPK signaling pathway in rats with adriamycin-induced nephropathy

作　　者：赵青[1] 万毅刚[2] 孙伟[3] 王朝俊[4] 魏晴雪[1] 陈好利[1] 孟宪杰[1] 

机构地区：[1]南京中医药大学中西医结合鼓楼临床医学院,江苏南京210029 [2]南京大学医学院附属鼓楼医院中医科,江苏南京210008 [3]江苏省中医院肾内科,江苏南京210029 [4]昆山市中医院,江苏昆山215300

出　　处：《中国中药杂志》2012年第19期2926-2934,共9页China Journal of Chinese Materia Medica

基　　金：南京市卫生青年人才培养工程项目;江苏高校优势学科建设工程项目

摘　　要：目的:阐明黄蜀葵花(Abelmoschus manihot,AM)提取物制剂———黄葵胶囊(Huangkui capsule,HKC)调节阿霉素肾病(adriamycin-induced nephropathy,ADRN)模型p38丝裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)信号通路从而改善肾组织炎症性损伤的机制。方法:将19只SD大鼠随机分为假手术组、对照组和HKC组。对HKC组和对照组大鼠行右侧肾摘除术,并在4周内分2次经颈静脉注射阿霉素(adriamycin,ADR)建立ADRN模型。HKC组大鼠于第2次注射ADR后经灌胃给予HKC悬浊液,对照组和假手术组大鼠同时经灌胃给予蒸馏水,共干预4周。在HKC和蒸馏水干预前和干预后第1,2,3,4周末,分别称量大鼠体重,并检测24 h尿蛋白排泄量(24 h urinary protein excretion,Upro)。肾摘除术后第8周末处死全部大鼠,抽取血液,摘除左肾并称重,观察血清生化指标、肾小球形态特征、肾小球α-平滑肌肌动蛋白(α-smooth mus-cle actin,α-SMA)、Ⅰ型胶原(collagen typeⅠ)表达特征、肾小球巨噬细胞(macrophage,MΦ)浸润特征等,并且检测肾组织转化生长因子(transforming growth factor,TGF)-β1,p38MAPK,磷酸化p38MAPK(phosphorylated p38MAPK,p-p38MAPK)蛋白相对表达量。结果:与对照组大鼠比较,HKC改善了模型鼠的蛋白尿和血清白蛋白(albumin,Alb),抑制了模型鼠系膜细胞(mesangialcell,MC)增殖、细胞外基质(extracellular matrix,ECM)及其胶原成分沉积,减轻了肾小球α-SMA,Ⅰ型胶原表达,减轻了肾小球ED1+,ED3+浸润,下调了模型鼠肾组织TGF-β1,p-p38MAPK蛋白表达。结论:HKC在体内具有减轻肾组织炎症性损伤的作用;HKC通过下调肾组织p38MAPK信号通路中关键信号分子———p-p38MAPK的蛋白表达,干预其相关信号通路的信号转导途径,减少肾组织内TGF-β1的表达和炎症细胞的浸润、活化,从而改善肾组织的炎症性损伤。Objective： To explore the potential mechanisms of Huangkui capsule（HKC）,an extract from Abelmoschus manihot（AM）,for ameliorating renal inflammatory injury by regulating p38 mitogen-activated protein kinase（MAPK）signaling pathway in rats with adriamycin-induced nephropathy（ADRN）. Method： Nineteen Sprague-Dawley（SD）rats were randomly divided into three groups,the sham-operation group,the untreated model group,and the HKC-treated group. Rats in the untreated model group and the HKC-treated group were made into ADRN model by right nephrectomy and twice intravenous injections of adriamycin（ADR,0.4 mL and 0.2 mL respectively within 4 weeks）. After the model successfully established,rats in the HKC-treated group were orally given HKC（2 mg·kg-1 per day）,while rats in the untreated model group and the sham-operation group were intervened with distilled water respectively. The intervention for all rats was 4 weeks. Rats＇body weight were weighted and 24 h urinary protein excretion（Upro）was detected at the end of the 1st,2nd,3rd,and 4th week after the intervention of HKC or distilled water. All rats were sacrificed at the end of the 8th week after nephrectomy,and then,to withdraw blood and kidney to examine the blood biochemical parameters,the glomerular morphological changes,α-smooth muscle actin（α-SMA）and collagen typeⅠexpressions,and the glomerular macrophages infiltration. Besides,the protein expression of transforming growth factor（TGF）-β1,p38MAPK,as well as phosphorylated p38MAPK（p-p38MAPK）in renal tissues were detected by Western blotting. Result： As compared with rats in the untreated model group,in the HKC-treated group,the HKC treatment significantly improved Upro,serum albumin,mesangial cell proliferation,extracellular matrix（ECM）and collagen deposition,and decreased the expression of α-SMA and collagen typeⅠ and the infiltration of ED1＋ and ED3＋ cells in glomeruli. In addition,it significantly down-regulated the protein expression of TGF-β1 and

关 键 词：黄葵胶囊 阿霉素肾病 炎症信号通路 P38MAPK 磷酸化P38MAPK 

分 类 号：R285[医药卫生—中药学]