基于转运体探讨何首乌提取物对大鼠肾脏的影响  

Effects of Polygonum multiflorum extract on rat kidneys based on transporters

作　　者：汪祺[1] 杨建波[1] 王莹[1] 马双成[1] 文海若 WANG Qi;YANG Jianbo;WANG Ying;MA Shuangcheng;WEN Hairuo(National Institutes for Food and Drug Control,Beijing 100050,China)

机构地区：[1]中国食品药品检定研究院,北京100050

出　　处：《中国药物警戒》2022年第6期626-629,640,共5页Chinese Journal of Pharmacovigilance

基　　金：国家自然科学基金资助项目(81973476)。

摘　　要：目的阐明向大鼠长期给药何首乌醇提物(PME)和水提物(PMW)对其肾脏的影响。方法分别向大鼠灌胃给药何首乌PME和PMW 42 d,考察大鼠生化指标及肾脏病理变化,并测定给药后肾脏主要转运体基因(Oat1,Oat2,Oct2,Mrp2,P-gp)的表达,从转运体角度分析何首乌致肾损伤的作用机制。结果研究发现PME和PMW给药后,血清生化PME组的尿素氮(BUN),肌酐(CRE),总蛋白(TP)和白蛋白(ALB)均显著升高(P<0.01),PMW组的BUN,CRE和TP显著升高(P<0.01),ALB数值升高,但不具统计学意义(P>0.05)。肾脏病理结果显示PME组和PMW组均可见肾脏色素沉着,PME组可见肾小管变性。基因表达检测结果发现,PME组Oat1,Oct2,P-gp和Mrp2均显著性下调(P<0.01),Oat2显著性上调(P<0.01)。PMW组Oat1,Oct2和Mrp2显著性下调(P<0.01),Oat2显著性上调(P<0.01),P-gp变化不具统计学意义(P>0.05)。结论经过长期给药,两种提取物均可引起大鼠肾脏损伤,且PME作用更显著。肾毒性作用机制可能与何首乌相关成分对肾脏转运体的影响相关,潜在肾毒性成分可能为二苯乙烯苷和大黄素。Objective To explore the effects of long-term administrations of Polygonum multiflorum ethanol extract(PME)and water extract(PMW) on kidneys of rats. Methods PME and PMW were administered to rats via oral gavage for 42days, and the biochemical indexes as well as renal pathological changes were examined. The expression levels of major kidney transporters(Oat1, Oat2, Oct2, Mrp2, P-gp) after administration were detected, and the mechanism of Polygonum multiflorum-induced renal injury was analyzed in terms of transporters. Results After the administration of PME and PME, the biochemical indexes of serum in the PME group, including blood urea nitrogen(BUN), creatinine(CRE), total protein(TP) and albumin(ALB), were significantly increased(P<0.01). In the PMW group, BUN, CRE and TP were significantly increased(P<0.01), but the increase in ALB was not statistically significant(P>0.05). Renal histopathologic results suggested renal pigmentation in both PME and PMW groups, but renal tubular degeneration was seen in the PME group only. Data on gene expression detection showed that Oat1, Oct2, P-gp and Mrp2 were significantly down-regulated(P<0.01), while Oat2 was significantly up-regulated(P<0.01) in the PME group. In the PMW group, Oat1, Oct2 and Mrp2 were significantly down-regulated(P<0.01), but Oat2 was significantly up-regulated(P<0.01), and the change in P-gp was not statistically significant(P>0.05). Conclusion After a long-term medication, both PME and PMW can lead to kidney injury in rats and the effect of PME is more prominent. The mechanism of action is associated with the effect of both extracts on renal transporters. The potential nephrotoxic components may be stilbene glycosides and emodin.

关 键 词：何首乌 何首乌醇提物 何首乌水提物 毒性 肾脏 转运体 大黄素 二苯乙烯苷 

分 类 号：R961[医药卫生—药理学] R962[医药卫生—药学]