中药肾毒性的研究进展

庄延双; 蔡宝昌; 张自力; 孟庆香

doi:10.14148/j.issn.1672-0482.2022.0390

中药肾毒性的研究进展

doi: 10.14148/j.issn.1672-0482.2022.0390

1.
南京中医药大学泰州附属医院, 江苏泰州 225300
2.
南京中医药大学药学院, 江苏南京 210023

基金项目:

国家自然科学基金青年科学基金项目 82000572

详细信息

作者简介:
庄延双, 女, 主管中药师, E-mail: 295331981@qq.com

通讯作者:
张自力, 男, 研究员, 主要从事中医药防治慢性肝病研究, E-mail: zilizhang88@163.com

中图分类号: R285.1
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- 被引次数: 0
出版历程
- 收稿日期: 2021-12-22
- 发布日期: 2022-05-10

Research Progress of Nephrotoxicity of Traditional Chinese Medicine

1.
Taizhou Hospital Affiliated to Nanjing University of Chinese Medicine, Taizhou 225300, China
2.
School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China

摘要

摘要: 中药在治疗疾病产生疗效的同时, 其毒性问题也不容忽视, 部分中药的不合理使用, 导致肾脏等器官损害。中药肾毒性的问题也逐渐引起国内外学者的广泛关注。笔者通过总结中药产生肾毒性的原因及作用机制、肾毒性的常用评价方法、降低中药肾毒性的策略等, 以期能较为全面地了解中药的肾毒性, 防止临床肾毒性不良反应的发生。
- 中药 /
- 肾毒性 /
- 评价方法 /
- 策略
Abstract: While traditional Chinese medicine has curative effect in the treatment of diseases, its toxic effect can not be ignored, especially the nephrotoxicity of traditional Chinese medicine can not be underestimated. This review mainly summarizes the causes and mechanism of nephrotoxicity of traditional Chinese medicine, common evaluation methods of nephrotoxicity and strategies to reduce nephrotoxicity, in order to comprehensively understand the nephrotoxicity of traditional Chinese medicine and prevent the occurrence of clinical nephrotoxic adverse reactions.
- traditional Chinese medicine /
- nephrotoxicity /
- evaluation methods /
- strategy

HTML全文

表 1 一些常见中药产生毒性原因、作用机制和毒性表现

Table 1. Causes, mechanisms and manifestations of toxicity of some common traditional Chinese medicines

中药	产生毒性原因	作用机制	毒性表现
雷公藤	含雷公藤甲素等毒性成分	氧化应激^[15]	临床表现为蛋白尿、血尿、氮质血症、酸中毒, 甚至逐渐或迅速出现少尿或无尿等, 严重者可导致肾衰竭而死亡; 肾脏病理表现为肾小管或间质出现明显炎症性细胞浸润, 肾小管上皮明显变性、坏死及萎缩^[16]。
益母草	含益母草生物碱等毒性成分	氧化损伤、内皮细胞损伤^[17]	病理表现为肾间质纤维化、肾毛细血管扩张或受压和肾小管管腔萎缩^[18]。
细辛	含马兜铃酸等毒性成分	促进氨基酸代谢、能量代谢、脂质代谢多种途径, 增加机体氧化损伤、放大炎症效应而发生细胞毒性^[19]	临床表现为蛋白尿, 肾脏病理表现为炎性浸润伴纤维组织增生和肾组织充血^[20]。
补骨脂	含补骨脂酚等毒性成分	损伤细胞膜、诱发细胞凋亡及抑制细胞增殖	临床表现为尿量减少^[21]。
大黄	含有大黄酸、大黄素、芦荟大黄素、蒽醌类等成分	调节死亡受体介导的凋亡通路和线粒体凋亡通路, 诱导细胞凋亡; 诱导细胞周期阻滞; 调节氧化应激、内质网应激通路相关的蛋白, 引起细胞凋亡; 激活MAPK通路	临床表现为尿素氮、K⁺、Ca²⁺和β₂微球蛋白以及总蛋白质升高, 肾脏病理表现为肾小管、肾小球、肾小管上皮细胞损伤、肾脏淋巴细胞增生等^[22]。
马兜铃	含马兜铃酸等毒性成分	内质网应激反应引起细胞凋亡、氧化应激引起脂质过氧化、免疫炎性机制、凋亡机制、肾小管上皮细胞转分化、缺血导致肾微血管损伤、代谢酶引起肾损伤	急性马兜铃酸肾病临床表现主要为少尿或非少尿性急性肾功能衰竭; 病理表现为急性肾小管坏死, 部分肾小管仅残留裸露基底膜, 肾间质水肿, 小动脉内皮细胞肿胀。慢性马兜铃酸肾病临床表现为肾性糖尿及轻度蛋白尿、低比重尿及低渗透压尿, 肾功能呈进行性损害; 病理表现为寡细胞性慢性肾间质纤维化, 可见肾间质呈多灶或大片状纤维化, 肾小管萎缩或消失, 肾小球基底膜呈缺血性皱缩。肾小管功能障碍型马兜铃酸肾病临床表现为肾小管性酸中毒和/或范可尼综合征, 同时伴浓缩功能障碍, 而血清肌酐及尿素氮基本正常; 病理改变主要为肾小管变性及萎缩, 部分崩解脱落, 电镜下可见肾小管刷状缘部分脱落, 上皮细胞线粒体肿胀, 部分细胞器崩解及脱落, 肾小球基本正常^[23]。
商陆	含商陆皂苷等毒性成分, 或未经炮制后使用	激动NF-κB信号, 磷酸化IκBα靶蛋白, 下游炎症因子TNF-α、IL-1β过量表达, 从而诱发肾脏损伤; 氧化应激引起细胞凋亡导致肾脏损伤	临床表现为血尿素氮、肌酐的显著升高, 病理表现为蛋白管型、肾小管上皮嗜碱性病变、肾小管间质纤维化^[24]。
苍耳子	含有苍术苷、羧基苍术苷及毒蛋白, 或误服鲜苍耳子, 或超剂量使用	脂质过氧化	临床表现为少尿、水肿、尿闭、血尿、尿失禁、肾功能异常、急性肾功能衰竭等^[25]。
朱砂、红粉和轻粉等	含有Hg, 高剂量或长期使用, 或未经炮制后使用	汞与富含巯基的蛋白质结合, 导致体内多种酶活性降低或者失活, 影响细胞膜的运输功能和能量代谢, 破坏线粒体的功能和磷酸化; 另外汞也可能引起脂质过氧化和氧化应激反应, 导致自由基增多, 推动氧化反应, 放大活性氧的作用, 导致细胞功能损伤^[26]	当汞浓度低, 肾损伤病变的早期, 仅有近曲小管损伤, 少量蛋白尿; 随着汞在体内蓄积量的增加, 肾损伤逐渐累及远小管、集合管系统, 使尿液浓缩功能受损, 致夜尿增多; 当汞在体内的蓄积量达到一定程度，出现中度至重度汞中毒时, 会出现肾小球损伤的临床表现, 大量蛋白尿、肾病综合征, 乃至肾功能不全^[27]。
蜈蚣	含有组织胺样物质、溶血性蛋白质及多肽毒素等毒性物质	水解酶破坏肾脏组织	急性肾功能衰竭死亡^[28]。
泽泻	大剂量长期使用	调节Kim-1、Ceruloplasmin、Clusterin、LCN2、Osteopontin和TIMP1等蛋白的表达^[29]	临床表现为水-电解质失衡以及血尿, 甚至发生肾小管酸中毒; 病理表现为肾间质炎症、细胞浸润和肾小管损伤^[30]。

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