六味地黄丸通过调控NF-κB及TGF-β/Smad双信号通路减轻糖尿病肾病炎症及纤维化  

Liuwei Dihuang Pills Alleviating Renal Inflammation and Fibrosis of Diabetic Nephropathy Through Regulating and Controlling NF-κB and TGF-β/Smad Double Signaling Pathways

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作  者:陶鹏宇 张悦 TAO Peng-Yu;ZHANG Yue;School of Basic Medical Sciences,Shanghai University of Traditional Chinese Medicine

机构地区:上海中医药大学基础医学院

出  处:《广州中医药大学学报》2019年第2期245-250,共6页Journal of Guangzhou University of Traditional Chinese Medicine

摘  要:【目的】基于核因子kappa B(NF-κB)及转化生长因子β(TGF-β)/Smad双信号通路,观察六味地黄丸对糖尿病肾病炎症及纤维化的影响,探讨其对肾保护作用机制。【方法】将30只SD大鼠随机分为正常组、模型组、中药组,每组10只。采用一次性腹腔注射链脲佐菌素法复制糖尿病大鼠模型。中药组给予大鼠六味地黄丸(剂量为6.75 g·kg-1·d-1)灌胃,正常组、模型组给予大鼠等体积生理盐水灌胃。给药12周后取材,检测各组大鼠空腹血糖(FBG)、尿素氮(BUN)、血肌酐(SCr)、24h尿蛋白量(24h-Pro),采用苏木素—伊红(HE)与Masson染色观察肾组织病理变化,蛋白免疫印迹(Western blot)法检测肾组织NF-κB、单核细胞趋化蛋白1(MCP-1)、TGF-β、alpha平滑肌抗体(α-SMA)、Smad2、Smad3、Smad7的表达。【结果】生化指标结果显示:与正常组比较,模型组大鼠FBG、BUN、SCr、24h-Pro升高(P<0.01);六味地黄丸治疗后上述指标均有所改善(P<0.05)。HE与Masson染色结果显示,模型组肾小球官腔变窄、系膜基质增生及炎症细胞浸润,而中药组有所改善。Western blot结果显示:与正常组比较,模型组的NF-κB、MCP-1、TGF-β、α-SMA、Smad2、Smad3表达均呈明显上调,而Smad7表达降低(P<0.01);中药组NF-κB、MCP-1、TGF-β、α-SMA、Smad2、Smad3表达下调,Smad7表达上调(P<0.05)。【结论】六味地黄丸具有肾脏保护作用,其机制可能与通过调控NF-κB及TGF-β/Smad双信号通路,从而减轻糖尿病肾病炎症损伤和纤维化有关。Objective To observe the effects of Liuwei Dihuang Pills on the renal inflammation and fibrosis of diabetic nephropathy based on nuclear factor kappa B(NF-κB)and transforming growth factorβ(TGF-β)/Smad double signaling pathways,and to explore its renal protective mechanism.Methods Diabetic rat model was established by one-dose intraperitoneal injection of streptozotocin.Thirty SD rats were randomly divided into normal group,model group and Chinese medicine group,10 rats in each group.Chinese medicine group was given intragastric administration of Liuwei Dihuang Pills(at the dosage of 6.75the normal group and model group were given intragastric administration of the same volume of normal saline.After medication for 12weeks,the blood was sampled for the detection of fasting blood glucose(FBG),blood urea nitrogen(BUN),serum creatinine(SCr)and 24-hour urine protein(24h-Pro).Pathological changes of renal tissues were observed by haematoxylin-eosin staining(HE)and Masson staining.The expression levels of NF-κB,monocyte chemotactic protein-1(MCP-1),TGF-β,alpha smooth muscle actin(α-SMA),drosophila mothers against decapentaplegic protein(Smad)2,Smad3 and Smad7 were detected by Western blotting method.Results The results of the detection of biochemical indexes showed that the levels of FBG,BUN,SCr and 24h-Pro were increased in the model group as compared with those in the normal group(P<0.01),while the above indexes were improved after the treatment with Liuwei Dihuang Pills(P<0.05).HE and Masson staining results showed that the model group had narrowing glomerular space,hyperplastic mesangial matrix expansion and inflammatory cell infiltration,but the above pathological changes were improved in Chinese medicine group.Western blotting results showed that the expression levels of NF-κB,MCP-1,TGF-β,α-SMA,Smad2 and Smad3 in the model group were significantly up-regulated,and the Smad7 expression level was down-regulated as compared with those in the normal group(P<0.01).The expression levels of NF-κB,MCP-1,TGF-β,�

关 键 词:六味地黄丸 糖尿病肾病 炎症 纤维化 NF-ΚB信号通路 TGF-Β/SMAD信号通路 疾病模型 动物 大鼠 

分 类 号:R285.5[医药卫生—中药学;医药卫生—中医学]

 

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