【摘要】 目的:探讨黄芪当归合剂(astragalus and angelica m ixture,A&A)对外源性马兜铃酸Ⅰ(aristoloch ic ac idⅠ,AAⅠ-)所造成的肾小管上皮细胞损伤的干预作用。方法:以体外培养的人近端肾小管上皮细胞系(HK-2)为研究对象,在AA-I(2.5 mg/L)刺激细胞4 h后,给予A&A药物血清并使细胞继续生长至48 h,应用流式细胞仪分析细胞DNA含量了解细胞凋亡情况;采用ELISA法检测细胞培养上清液中纤维连接蛋白(fibronectin,FN)及转化生长因子β1(transform ing growth factor-beta 1,TGFβ-1)分泌水平;比较A&A干预前后AA-I诱导的细胞凋亡、TGF-β1及FN分泌的改变。结果:正常HK-2细胞能够分泌少量TGFβ-1(7.05±1.98μg/L),正常血清与A&A均不能够诱导TGFβ-1的明显分泌(6.35±1.99μg/L and 6.57±2.19μg/L,vs.对照组,P>0.05),AAⅠ-能够诱导细胞分泌TGFβ-1(18.26±5.98μg/L,vs.对照组,P<0.05),与AA-I作用组相比,A&A能够抑制TGFβ-1分泌(6.66±0.70μg/L,vs.AA-I,P<0.05),抑制率达63.5%;A&A还能够阻断细胞凋亡,阻断率达93.7%(3.32%±0.41%vs.19.19±6.32%,A&A+AA-Ivs.AA-I,P<0.001),并能抑制AA-I诱导HK-2细胞分泌(1.64±1.11倍vs.2.93±0.87倍,P<0.05),抑制率达44%。结论:A&A能够减轻AAⅠ-诱导的肾小管上皮细胞损伤,其机制可能与抑制TGFβ-1的作用有关。更多还原

【Abstract】 Objective:To investigate whether Chinese herb astragalus and angelica mixture(A&A) have influence on the renal tubular epithelial cell injury induced by aristolochic-acid I.Methods:Human proximal tubular epithelial cell line HK-2 was pre-treated with AA-I(2.5 mg/L)for 4 hours.Cells were then treated with or without A&A for additional 44 hours.Cell apoptosis was evaluated by using FACS.Secreted fibronectin(FN) and TGF-β1 levels were assayed by ELISA.The changes of AA-I-induced FN,TGFβ1 level and the rate of apoptosis were compared before and after A&A treatment.Results:There was basement secretion of TGF-β1 by HK-2 cells(7.05±1.98 μg/L).Both normal serum(N-S) and A&A could not induce the cells to secret TGF-β1(6.35±1.99 μg/L and 6.57±2.19 μg/L,vs.control,P>0.05).AA-I could induce the TGF-β1 secretion by HK-2 cells(18.26±5.98 μg/L,vs.control,P<0.05).A&A could block AA-I-induced TGF-β1 secretion by 63.5%(6.66±0.70 μg/L,vs.AA-I,P<0.05).It also suppressed AA-I-induced cell apoptosis by 93.7%(3.32%±0.41% vs.19.19%±6.32% respectively,P<0.001)and FN secretion by 44%(1.64±1.11 folds vs.2.93±(0.87) folds respectively,P<0.05).Conclusion:A&A inhibits AA-I induced injury in human renal proximal tubule epithelial cells,whose mechanism may be partially through blocking TGF-β1 secretion.更多还原