摘要
目的探讨大黄附子汤干预腺嘌呤所致慢性肾衰竭的疗效及可能作用机制。方法将雄性KM小鼠随机分为正常组、模型组、地塞米松组及大黄附子汤低、中、高剂量组,每组15只。除正常组外,其余各组采用腺嘌呤致小鼠慢性肾衰竭模型,实验第3周起,大黄附子汤低、中、高剂量组每天给予浓度为0.84、4.2、42mg/g大黄附子汤灌胃,灌胃体积1ml/20g;地塞米松组小鼠首次灌胃剂量为0.06mg/kg,维持剂量0.015mg/kg;正常组和模型组小鼠给予生理盐水1ml/20g灌胃。各组均每日灌胃1次,共3周。记录各组小鼠一般情况,实验结束后测小鼠体重,计算肾脏系数,检测肾功能[包括尿素氮(BUN)、血肌酐(Scr)]、电解质(包括K^+、Na^+、Cl^-)及外周血转化生长因子β1(TGF-β1)、骨形态发生蛋白7(BMP-7)水平,取肾组织做病理切片HE染色,检测肾组织Smad 6、P38蛋白表达。结果模型组小鼠肾组织病理呈现肾小球变性、数量减少、球囊粘连,肾间质胶原沉积,出现明显间质纤维化;与模型组比较,地塞米松组和大黄附子汤低、中、高剂量组肾脏组织病变改善,其中大黄附子汤高剂量组改善效果最显著。与模型组比较,大黄附子汤各剂量组小鼠体重、肾脏系数、外周血BMP-7水平均升高,TGF-β1及Cl^-水平均下降(P<0.05);并且大黄附子高剂量组在降低小鼠BUN、Scr及TGF-β1方面、升高BMP-7水平及肾组织Smad 6蛋白表达方面优于大黄附子中、低剂量组(P<0.05)。结论大剂量大黄附子汤可改善腺嘌呤所致慢性肾衰竭小鼠肾功能和肾脏病理,其机制可能通过TGF-β1/BMP-7及Smads信号通路来减轻或阻止肾纤维化的发展。
Objective To investigate the effect and possible mechanism of Dahuang Fuzi Decoction(大黄附子汤)on adenine-induced chronic renal failure.Methods Male KM mice were randomly divided into a normal group,a model group,a dexamethasone group and Dahuang Fuzi Decoction low,medium and high dose groups,with 15 mice in each group.Except the normal group,the other groups used adenine to induce chronic renal failure model mice.From the third week of the experiment,the low,medium,and high dose groups of Dahuang Fuzi Decoction were administered with daily concentrations of 0.84,4.2,and 42 mg/g Dahuang Fuzi Decoction by gavage.The volume of gavage was 1 ml/20 g;the first dose of gavage in the dexamethasone group was 0.06 mg/kg,and the maintenance dose was 0.015 mg/kg;the mice in the normal group and the model group were gavage with normal saline 1 ml/20 g.All groups were administrated by gavage once a day for 3 weeks.The general situation of the mice was recorded,and the body weight of the mice was measured after the experiment.The kidney coefficient was calculated.The renal function including blood urea nitrogen(BUN),serum creatinine(Scr),electrolytes including K^+,Na^+,Cl^-and the periphery blood transforming growth factorβ1(TGF-β1)and bone morphogenetic protein 7(BMP-7)levels were detected.Renal tissue was taken for pathological section with HE staining,and the expression of Smad 6,P38 protein in renal tissue was detected.Results In the model group,the renal tissue pathology showed glomerular degeneration,decreased number,balloon adhesion,renal interstitial collagen deposition,and obvious interstitial fibrosis.Compared with the model group,the renal tissue lesion in the dexamethasone group and Dahuang Fuzi Decoction low,medium and high dose groups were improved,and the improvement effect of Dahuang Fuzi Decoction high dose group was the most significant.Compared with the model group,the body weight,kidney coefficient,and BMP-7 levels of peripheral blood of mice in each dose group of Dahuang Fuzi Decoction increased,and the levels of TGF-β1 and Cl decreased(P<0.05).Dahuang Fuzi Decoction high dose group was better in decreasing BUN,Scr,and TGF-β1 in mice,increasing BMP-7 levels,and Smad 6 protein expression in kidney tissues were better than Dahuang Fuzi Decoction low,medium dose groups(P<0.05).Conclusion Dahuang Fuzi Decoction high dose group can improve renal function and renal pathology in adenine-induced chronic renal failure mice.The mechanism may reduce or prevent the development of renal fibrosis through the TGF-β1/BMP-7 and Smads signaling pathways.
作者
张琳琳
张海晨
宋云霄
李玉虎
ZHANG Linlin;ZHANG Haichen;SONG Yunxiao;LI Yuhu(Central Hospital of Xuhui District,Shanghai,200031;Shanghai University of Traditional Chinese Medicine)
出处
《中医杂志》
CSCD
北大核心
2019年第24期2138-2142,共5页
Journal of Traditional Chinese Medicine
基金
上海徐汇区医学科研青年项目(SHXH201734)
关键词
慢性肾衰竭
大黄附子汤
肾纤维化
肾功能
电解质
转化生长因子β1
骨形态发生蛋白7
chronic renal failure
Dahuang Fuzi Decoction(大黄附子汤)
renal fibrosis
renal function
electrolytes
transforming growth factorβ1
bone morphogenetic protein 7
