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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

Keywords: 黄葵胶囊,阿霉素肾病,炎症信号通路,p38MAPK,磷酸化p38MAPK

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Abstract:

目的:阐明黄蜀葵花(Abelmoschusmanihot,AM)提取物制剂——黄葵胶囊(Huangkuicapsule,HKC)调节阿霉素肾病(adriamycin-inducednephropathy,ADRN)模型p38丝裂原活化蛋白激酶(mitogen-activatedproteinkinase,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24h尿蛋白排泄量(24hurinaryproteinexcretion,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-smoothmuscleactin,α-SMA)、Ⅰ型胶原(collagentypeⅠ)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(transforminggrowthfactor,TGF)-β1,p38MAPK,磷酸化p38MAPK(phosphorylatedp38MAPK,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(extracellularmatrix,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。

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