中国中药杂志

2004, (01)

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马兜铃内酰胺I对肾小管上皮细胞的损伤作用
Injury in renal proximal tubular epithelial cells Induced by aristololactam I

李彪,李晓玫,张翠英,王璇,蔡少青
LI Biao 1, LI Xiao-mei 1, ZHANG Cui-ying 2, WANG Xuan 2, CAI Shao-qing 2 (1.Renal Division, Department of Medicine, First Hospital,Peking University , Beijing 100034, China; 2.School of Pharmaceutical Sciences, Peking Unive rsity,Beijing 100034, China)

摘要(Abstract):

目的 :了解马兜铃内酰胺I(AL I)是否导致肾小管上皮细胞损伤。方法 :以体外细胞培养的人类近端肾小管上皮细胞系 (HK 2 )为研究对象 ,以马兜铃酸I(AA I)为阳性对照 ,采用LDH释放试验检测AL I的直接细胞损伤作用 ;用相差显微镜、电子显微镜观察细胞形态变化 ,用流式细胞仪分析细胞DNA含量以及细胞膜磷脂酰丝氨酸 (PS)表达水平 ,以了解细胞凋亡情况 ;采用ELISA法检测细胞培养上清液中细胞外基质成分纤连蛋白 (FN)以及促纤维化细胞因子转化生长因子 β1(TGFβ1)的分泌水平。 结果 :AL I(2 .5~ 2 0mg·L- 1)具有浓度依赖的直接细胞损伤作用 ;细胞形态、DNA含量及PS表达水平分析表明 ,AL I在上述浓度范围内能够导致HK 2细胞凋亡 ,并能够导致HK 2细胞分泌TGFβ1及FN。与AA I的作用进行比较发现 :在相同浓度情况下 ,AL I的直接细胞毒作用强于AA I,但其导致细胞凋亡、TGFβ1及FN分泌的能力弱于AA I。结论 :马兜铃酸的代谢产物AL I能够造成肾小管上皮细胞的损伤 ,作用与AA I相似。尽管其致损伤作用较AA I弱 ,但仍有可能是含马兜铃酸中药导致肾脏损伤及其纤维化过程的毒性成分之一。
Objective: To study whether aristololactam I (AL-I) induces injury i n human renal proximal tubular epithelial cells. Method: C ultured human renal p roximal tubular epithelial cell line HK-2 was used as the subject. Aristolochic Acid I(AA-I) was used as a positive control. Cell toxicity of AL-I was detecte d by LDH releasing rate. Cell apoptosis was evaluated by cellular morphology, DNA content and expression of cell membrane phosphatidylserine(PS). The secretion level of fibronectin (FN) and TGF-β1 in HK-2 cells were assayed by ELISA. Result : AL-I had a direct toxicity on HK-2 in a dose dependent manner fr om 2.5 mg·mL -1 to 20 mg·mL -1 ; In these range of concentration, AL-I could induce cell a poptosis w hich was detectable by measurements of morphology, DNA content and expression of PS. AL-I could stimulate the secretion of FN and TGF-β1. The potency of AL- I ce ll toxicity was higher than AA-I at the same concentration. The effects of AL- I on apoptosis, secretion of FN and TGF-β1 were all weaker than AA-I. Conclusion: AL-I as one metabolite of AA-I in vivo induces direct injury in renal proxi mal tubular cells. Its effects are similar to those of AA-I. AL-I may be one o f toxic metabolites in Chinese herbs containing AA which participate in renal da mage and fibrosis.TGF β1wereallweakerthanAA I.Conclusion :AL

关键词(KeyWords): 马兜铃内酰胺I;马兜铃酸I;肾小管上皮细胞;细胞凋亡;纤维化
aristololactam I; aristolochic acid I; ren al tubular epithelial cell; apoptosis; fibrosis

Abstract:

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基金项目(Foundation): 中国教育部教育振兴行动计划(985项目)专项基金

作者(Author): 李彪,李晓玫,张翠英,王璇,蔡少青
LI Biao 1, LI Xiao-mei 1, ZHANG Cui-ying 2, WANG Xuan 2, CAI Shao-qing 2 (1.Renal Division, Department of Medicine, First Hospital,Peking University , Beijing 100034, China; 2.School of Pharmaceutical Sciences, Peking Unive rsity,Beijing 100034, China)

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