大黄酸对马兜铃酸A引起的斑马鱼肾脏损伤的保护作用  

Protective effect of rhein on aristolochic acid-induced renal injury in zebrafish

作　　者：王雪[1] 刘可春[1] 王希敏[1] 韩利文[1] 张姗姗[1] 何秋霞[1] 陈锡强[1] 韩建[1] 王荣春[1] 

机构地区：[1]山东省科学院生物研究所山东省科学院斑马鱼药物筛选平台山东省生物传感器重点实验室,山东济南250014

出　　处：《中国药理学通报》2016年第3期361-365,共5页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81202584;31400979);山东省自主创新重大专项(No 2014ZZCX0215)

摘　　要：目的观察大黄酸在马兜铃酸A引起的斑马鱼肾脏损伤中的作用。方法将肾脏发育完成的斑马鱼仔鱼(4dpf)用马兜铃酸A处理24 h,造成马兜铃酸肾病模型,同时加入大黄酸处理,然后观察仔鱼的表型变化情况,并用肌酐检测试剂盒测定仔鱼组织中的肌酐含量,利用q PCR对仔鱼组织中的炎性相关因子(cox2a)和致纤维化因子(TGFβ-1)进行定量检测。结果马兜铃酸A处理24h后,部分仔鱼出现眼周水肿及血循环系统异常,表现为心跳微弱,心腔缩小,血流缓慢甚至停滞,发生率具有剂量相关性,马兜铃酸处理组仔鱼组织中的肌酐含量比对照组明显升高,cox2a和TGFβ-1表达量也比对照组明显上升,同时加入大黄酸能降低异常仔鱼所占比例,降低组织肌酐含量,并下调cox2a的表达,但对马兜铃酸引起的TGFβ-1的上升无影响。结论大黄酸对马兜铃酸引起的斑马鱼肾脏损伤有一定的保护作用。Aim To study the effect of rhein on renal damage induced by aristolochic acid.Methods Zebrafish model of aristolochic acid nephropathy,generated by treating zebrafish larvae with aristolochic acid for 24 h,was treated with rhein simultaneously.Morpholigical changes were observed and the creatinine level in larvae tissue was measured.And mRNA expression levels of inflammatory factor cox2 a and fibrosis factor TGF-β1 in larvae tissue were detected using qPCR.Results Some larvae show periocular edema and circulation system defection e.g.weak heart beat,narrow cardiac vesicle,decreased blood flow and even blockage,with a dose-response relationship after exposure to aristolochic acid for 24 h.The creatinine level in larvae tissue of the treated group was significantly higher than that of the control larvae.And the expression levels of cox2 a and TGF-β1 in larvae tissue of the treated group were also significantly increased.Percentage of abnormal larvae and creatinine level in larvae tissue were decreased when treated with rhein simultaneously.And the expression levels of cox2 a was down-regulated by rhein compared with the aristolochic acid treated group.But rhein had no effect on TGF-β1expression.Conclusion To some extent rhein can protect renal from damage induced by aristolochic acid.

关 键 词：马兜铃酸 斑马鱼 仔鱼 肾脏 大黄酸 肌酐 

分 类 号：R-332[医药卫生] R284.1