马兜铃酸及马兜铃科中药临床使用风险差异研究

doi:10.19803/j.1672-8629.20210325

摘要/Abstract

摘要： 目的梳理马兜铃酸毒性与马兜铃科中药的差异,为有毒中药临床合理使用提供借鉴和参考,避免公众混淆。方法通过文献调研,回顾含马兜铃酸制品引发的安全用药问题,梳理含马兜铃酸中药的使用风险,同时总结既往马兜铃酸减毒研究。结果马兜铃酸问题与马兜铃科中药两者本质不同,遵循中医药理论指导,临床合理使用含马兜铃科中药,不会引起严重不良反应。结论建议提高我国有毒中药的科学监管能力和水平,避免盲目的中医药毒性或安全性质疑,为中药行业发展注入积极力量。

关键词: 马兜铃酸, 马兜铃科, 减毒, 科学监管

Abstract: Objective To study the difference between aristolochic acid toxicity and Aristolochiaceae in order to provide reference for rational use of toxic traditional Chinese medicines (TCM) and prevent confusion. Methods A series of problems with safe medication caused by aristolochic acid products was retrospectively analyzed through literature review. The risks of using Aristolochiaceae were summarized, and previous studies on aristolochic acid reduction were outlined. Results The problems caused by aristolochic acids were essentially different from those by Aristolochiaceae. Compliance with theories of TCM and rational use of Aristolochiaceae will not cause serious adverse reactions. Conclusion More rigorous supervision of toxic TCM are recommended. Irrational fears about the toxicity of TCM should be eliminated so as to boost the development of TCM industry.

Key words: aristolochis acids, aristolochiaceae, detoxification, scientific supervision

中图分类号:

朱文静, 张立丹, 周玥, 雷海民. 马兜铃酸及马兜铃科中药临床使用风险差异研究[J]. 中国药物警戒, 2022, 19(11): 1213-1217.

ZHU Wenjing, ZHANG Lidan, ZHOU Yue, LEI Haimin. Risk difference between aristolochic acid and clinical use of traditional Chinese medicines in aristolochiaceae[J]. Chinese Journal of Pharmacovigilance, 2022, 19(11): 1213-1217.

参考文献

[1] VANHERWEGHEM JL, DEPIERREUX M, TIELEMANS C, et al.Rapidly progressive interstitial renal fibrosis in young women: Association with slimming regimen including Chinese herbs[J]. Lancet, 1993, 341(8842): 387-391.
[2] NG AW, POON SL, HUANG MN, et al.Aristolochic acids and their derivatives are widely implicated in liver cancers in Taiwan and throughout Asia[J]. Science Translational Medicine, 2017, 412(9): 6446.
[3] DE BROE ME.On a nephrotoxic and carcinogenic slimming regimen[J]. American Journal of Kidney Diseases, 1999, 33(6): 1171-1173.
[4] CHU CX, ZHU GF.Progress in aristoloid nephropathy[J]. Journal of Chinese Patent Medicine(中成药), 2020, 42(9): 2407-2412.
[5] GONG SJ.Aristolochic acid and nephrotoxicity[J]. Chinese Journal of Pharmacovigilance(中国药物警戒), 2004, 1(2): 34-35.
[6] STEFANOVIC V, TONCHEVA D, ATANASOVA S, et al.Etiology of balkan endemic nephropathy and associated urothelial cancer[J]. American Journal of Nephrology, 2006, 26(1): 1-11.
[7] YANG YL, WANG YL, GUI XJ.Retrospective analysis of rational use of aristolochia manshuriensis[J]. Chin J Mod Appl Pharm(中国现代应用药学), 2020, 37(23): 2925-2931.
[8] National Medical Products Administration. Notice on Cancelling the Medicinal Standard of A ristolochia manshuriensis Kom[EB/OL]. (2003-04-01)[2022-08-20]. https://www.nmpa.gov.cn/xxgk/fgwj/gzwj/gzwjyp/20030401010101717.html.
[9] National Medical Products Administration Notice on Strengthening the Supervision and Management of Six Medicinal Materials and Their Preparations including A ristolochia fangchi[EB/OL]. (2004-08-05)[2022-08-20]. https://www.nmpa.gov.cn/xxgk/fgwj/gzwj/gzwjyp/20040805010101598.html.
[10] National Food and Drug Administration. List of aristoliferous herbs that may contain aristolochic acid[EB/OL]. (2017-10-30)[2021-04-06]. http://www.sda.gov.cn/WS01/CL1991/215894.html.
[11] MARK L, TANYA Z, FRANCIS J, et al.Structure and stability of DNA containing an aristolactam II-dA lesion: implications for the NER recognition of bulky adducts[J]. Nucleic Acids Research, 2012, 40(6): 2759-2770.
[12] STIBOROVÁ M, FREI E, BREUER A, et al.Aristolactam I a metabolite of aristolochic acid I upon activation forms an adduct found in DNA of patients with Chinese herbs nephropathy[J]. Exp Toxicol Pathol, 1999, 51(4): 421-427.
[13] MEI N, ARLT VM, PHILLIPS DH, et al.DNA adduct formation and mutation induction by aristolochic acid in rat kidney and liver[J]. Mutation Research, 2006, 602(1): 83-91.
[14] SCHMEISER HH, SCHOEPE KB, WIESSLER M.DNA adduct formation of aristolochic acid I and II in vitro and in vivo[J]. Carcinogenesis, 1988, 9(2): 297-303.
[15] MA HY, WU JJ, GE GB, et al.Research progress in metabolism and virus process of aristolochic acid[J]. World Science and Technology-Modernization of Traditional Chinese Medicine(世界科学技术-中医药现代化), 2019, 21(2): 182-189.
[16] MA YM, WANG YH, SONG MQ, et al.Effect of Huang and Guan Mu on a content of aristolochic acid[J]. Shanxi Journal of Traditional Chinese Medicine(山西中医), 2015, 31(7): 57-58.
[17] LIANG Q, XIE M, Ni C, et al.Metabolomics study with astragalus[J]. Journal of Zhejiang University of Traditional Chinese Medicine(浙江中医药大学学报), 2010, 34(1): 42-43.
[18] WU JH, LI HX, WU C.Determination of aristolochic acid content in plasma of guided red dispersion and compatibility group by HPLC[J]. Journal of Hubei School of Traditional Chinese Medicine(湖北中医学院学报), 2010, 12(4): 30-32.
[19] WU C.Experimental study on the determination of A content of aristolochic acid in the guided red dispersion and its compatibility group by HPLC method[D]. Wuhan: Hubei College of Traditional Chinese Medicine, 2009.
[20] ZHANG C, CHEN YP, YANG YF, et al.Protective effects of yishen ruanjian power on renal interstitial fibrosis in chronic aristolochic acid induced nephropathy rat model[J]. Journal of Chinese Integrated Traditional Chinese and Western Medicine(中国中西医结合杂志), 2005, 25(8): 714-718.
[21] GUO YC, LI RF, WANG XG, et al.Intervention of ginseng and prednisone on acute nephrotoxicity in rats[J]. Journal of Chinese Integrated Traditional Chinese and Western Medicine(中国中西医结合急救杂志), 2005, 12(5): 292-296.
[22] CHEN JL, WU YH, DENG YY, et al.Protection study of tubular epithelial cell damage caused by aristolochic acid[J]. Chinese Journal of Integrated Traditional Chinese and Western Medicine nephropathy(中国中西医结合肾病杂志), 2005, 6(8): 445-448.
[23] GU J, QIU Y, LONG SJ.Determination of total aristolochic acid in Guanmutong decoction and effects of rhubarb and Chuanxiong on acute nephrotoxicity in rats induced by Guanmutong[J]. Journal of Traditional Chinese Medicine(中药材), 2005, 28(8): 695-697.
[24] ZHANG MF, SHEN YQ, ZHANG YX.Progress in the protection effect and clinical application of glycyrrhizic acid on renal injury[J]. Journal of Modern Medicine and Clinic(现代药物与临床), 2012, 27(6): 655-659.
[25] YANG YF.Study on the protection effect of Panax notoginseng total saponin on the kidney damage of cisplatin and aristolochic acid[D]. Nanning: Guangxi Medical University, 2012.
[26] WANG X, HAN LW, HE QX, et al.Protection of rhubarb aric acid in toxic renal function injury[J]. Chinese Journal of Pharmacology and Toxicology(中国药理学与毒理学杂志), 2016, 30(10): 1052-1053.
[27] SUN XY, SUN QS, JIA LY.Determination of A of arioxine seeds by HPLC[J]. Shenyang Pharmaceutical University(沈阳药科大学学报), 2009, 26(4): 299-302.
[28] HOU SH, LI JJ, HAN LT, et al.Determination of aristolochic acid in different medicinal sites[J]. Journal of Hubei University of Chinese Medicine(湖北中医药大学学报), 2018, 20(6): 42-44.
[29] ZHANG YM, LI YS, SUN WX, et al.Comparison study of aristolochic acid and its artillery products[J]. Modern Distance Education of Chinese Traditional Chinese Medicine(中国中医药现代远程教育), 2012, 10(6): 154-156.
[30] JIANG X, WANG ZM, YOU LS, et al.RP-HPLC measured the content of aristolochic A in different regions[J]. Journal of Traditional Chinese Medicine(中国中药杂志), 2004, 29(5): 28-30.
[31] ZHANG CH, CAO R, LI QQ, et al.Comparison of methods[J]. Chinese Journal of Experimental Prescriptions(中国实验方剂学杂志), 2012, 18(10): 149-152.
[32] ZHANG Y, XIAO R, HUANG J, et al.HPLC fingerprint analysis before and after istoloid honey in different regions[J]. Chinese Journal of Pharmacy(中国药学杂志), 2017, 52(16): 1397-1402.
[33] SUN KX, ZHENG RS, ZHANG SW, et al.Report of cancer incidence and mortality in different areas of China, 2015[J]. China Cancer(中国肿瘤), 2019, 28(1): 1-11.
[34] CHEN SZ, DONG YP, WEN W, et al.Thoughts on carcinogen disputes and drug safety of aristoloc[J]. Second Military Medical University(第二军医大学学报), 2021, 42(1): 1-7.
[35] JI XJ, FENG GS, CHEN G, et al.Lack of correlation between aristolochic acid exposure and hepatocellular carcinoma[J]. Science China (Life Sciences), 2018, 61(6): 727-728.
[36] Chinese Pharmacopoeia Commission.Pharmacopoeia of People’s Republic of China(中华人民共和国药典)[S]. Beijing: China Medical Science Press, 2020.
[37] WANG PL, GUO WB, HUANG GR, et al.Berberine-based heterogeneous linear supramolecules neutralized the acute nephrotoxicity of aristolochic acid by the self-assembly strategy[J]. ACS Applied Materials & Interfaces, 2021, 13(28): 32729-32742.
[38] ZHANG PF.Clinical significance analysis of neutrotrophil-lymphocyte ratio (NLR) and cancerous neutroils in patients with hepatocellular liver cancer[D]. Nanjing: Nanjing University, 2016.