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黄芪当归合剂抑制马兜铃酸Ⅰ导致的肾小管上皮细胞损伤 被引量:7

Astragalus and angelica mixture inhibits the renal tubular epithelial cell injury induced by aristolochic-acid Ⅰ
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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。 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, TGF-β1 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±1.99μg/L and 6.57±2.19μg/L, vs. control, P〉0.05 ). AA-Ⅰ could induce the TGF-β1 secretion by HK-2 cells( 18.26±5.98μg/L, vs. control, P 〈0.05 ). A&A could block AA-Ⅰ-induced TGF-β1 secretion by 63.5% (6.66±0.70μg/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 ). ConclusAion: A&A inhibits AA-Ⅰ induced injury in human renal Proximal tubule epithelial cells, whose mechanism may be oartiallv through blockingh TGF-β1 secretion.
出处 《北京大学学报(医学版)》 CAS CSCD 北大核心 2006年第4期381-384,共4页 Journal of Peking University:Health Sciences
基金 国家自然科学基金(30330710) 教育部教育振兴行动计划特殊专项("九八五"工程)资助~~
关键词 马兜铃酸 上皮细胞 肾小管 细胞凋亡 细胞外基质 当归 黄芪 复方合剂 Aristolochic Acid Epithelial cells,kidney tubules Apoptosis Extracellular matrix Angelica sinensis, astragalus membranaceus,drug combinations
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