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中华肾病研究电子杂志

中华肾病研究电子杂志 ›› 2018, Vol. 07 ›› Issue (01) : 23 -27. doi: 10.3877/cma.j.issn.2095-3216.2018.01.006

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马兜铃属中草药肾毒性带来的思考
王小琴1,†(), 许文成1   
  1. 1. 430064　武汉，湖北省中医院、湖北中医药大学附属医院、湖北省中医药研究院
  • 收稿日期:2017-11-24 出版日期:2018-02-28
  • 通信作者: 王小琴
  • 基金资助:
    国家自然科学基金(81573907)

Reflections on the nephrotoxicity of Chinese herbs genus Aristolochia

Xiaoqin Wang1,†(), Wencheng Xu1   

  1. 1. Hubei Provincial Hospital of Traditional Chinese Medicine, Affiliated Hospital of Hubei University of Chinese Medicine, Hubei Provincial Academy of Traditional Chinese Medicine, Wuhan 430064, Hubei Province, China
  • Received:2017-11-24 Published:2018-02-28
  • Corresponding author: Xiaoqin Wang
  • About author:
    Corresponding author: Wang Xiaoqin, Email:
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王小琴, 许文成. 马兜铃属中草药肾毒性带来的思考[J]. 中华肾病研究电子杂志, 2018, 07(01): 23-27.

Xiaoqin Wang, Wencheng Xu. Reflections on the nephrotoxicity of Chinese herbs genus Aristolochia[J]. Chinese Journal of Kidney Disease Investigation(Electronic Edition), 2018, 07(01): 23-27.

近来Sci Transl Med以封面故事报道马兜铃酸(AA)的毒性事件后，再次引起公众对马兜铃属中草药安全性的质疑。本文以"中草药肾病"病例报道为起点，对"AA肾病"、"巴尔干肾病"的发现过程及三者的关联进行梳理。同时，从患者体内研究证实AA导致肾小管上皮细胞损伤、动物体内和体外实验研究显示AA干扰微小RNA、内质网应激或氧化应激导致肾脏细胞凋亡以及AA介导的炎症损伤等方面分析肾毒性发生机制；并阐明AA肾毒性事件带给我们的启示，以期国家各级药品监管部门对含AA的中草药进一步加强监管，期待开展新的临床流行病学研究，更新我国马兜铃属中草药造成的AA肝肾毒性发病情况。

关键词: 马兜铃酸, 马兜铃酸肾病, 马兜铃属, 肾毒性

Recently, Translational Medicine reported on the toxicities of aristolochic acid (AA) in its cover story, which once again caused the public to question the safety of genus Aristolochia herbs. This article started with the case report of "Chinese herbal nephropathy", and combed the discovery process of "AA nephropathy" and "Balkan endemic nephropathy" as well as the relationship among the three. At the same time, the mechanism of nephrotoxicity was analyzed based on the following aspects: clinical in vivo studies have confirmed that AA caused renal tubular epithelial cell damage; animal in vivo and in vitro studies have shown that AA interfered with microRNA; and endoplasmic reticulum stress or oxidative stress led to renal cell apoptosis and AA-mediated inflammatory injury, etc, which introduced the enlightenment from the AA nephrotoxicity events, in order to expect further strengthening supervision of Chinese herbs containing AA at all levels of drug regulatory authorities of our country, and carrying out new clinical epidemiological studies to update the incidences of AA hepatotoxicity and nephrotoxicity caused by the Chinese herbal medicine genus Aristolochia in China.

Key words: Aristolochic acid, Aristolochic acid nephropathy, Genus Aristolochia, Nephrotoxicity
表1 "防己"药材信息
药材名 属名 拉丁名 2015版《中国药典》
防己(别名：汉防己、粉防己) 千金藤属 Stephania tetrandra S. Moore 收载
木防己 木防己属 Cocculus trilobus (L.) DC 未收载
广防己 马兜铃属 Aristolochia fangchi Y．C. Wu et Hwang 未收载
汉中防己 马兜铃属 Aristolochia heterophylla Hemsl 未收载
[1]
Ng AWT, Poon SL, Huang MN, et al. Aristolochic acids and their derivatives are widely implicated in liver cancers in Taiwan and throughout Asia [J]. Sci Transl Med, 2017, 9(412): eaan6446.
[2]
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.
[3]
Vanhaelen M, Vanhaelen-Fastre R, But P, et al. Identification of aristolochic acid in Chinese herbs [J]. Lancet, 1994, 343(8890): 174.
[4]
Cosyns JP, Jadoul M, Squifflet JP, et al. Chinese herbs nephropathy: A clue to Balkan endemic nephropathy? [J]. Kidney Int, 1994, 45(6): 1680-1688.
[5]
薄玉红，毕增祺，何祖根，等. 中药马兜铃引起的大鼠非坏死性急性肾小管损伤和细胞凋亡初步研究 [J]. 中华肾脏病杂志，1997, 13(5): 52-53.
[6]
张勉之，郑法雷. 马兜铃酸肾毒作用的研究进展(从"中草药肾病"到"马兜铃酸肾病") [J]. 中国实用内科杂志，2004, 24(1): 56-58.
[7]
Chen HY, Ma BY, Grant A, et al. Time to abandon the term "Chinese herbs nephropathy" [J]. Kidney Int, 2001, 60(5): 2039-2040.
[8]
Solez K, Daugirdas J, Gregory MC, et al. Is "Chinese herbs nephropathy" a prejudicial term? [J]. Am J Kidney Dis, 2001, 38(5): 1141-1142.
[9]
Gillerot G, Jadoul M, Arlt VM, et al. Aristolochic acid nephropathy in a Chinese patient: Time to abandon the term "Chinese herbs nephropathy" ？ [J]. Am J Kidney Dis, 2001, 38(5): E26.
[10]
Cosyns JP. When is "aristolochic acid nephropathy" more accurate than "Chinese herbs nephropathy" ？ [J]. Kidney Int, 2002, 61(3): 1178.
[11]
Vanherweghem JL. Chinese herbs nephropathy: not merely a trivial matter of a name [J]. Am J Kidney Dis, 2002, 40(1): 218.
[12]
Kazantzis G. Comment in the general discussion: possible nephrotoxic agents[M]// Wolstenholme GE, Knight J. The Balkan nephropathy. Boston: CIBA Foundation, 1967: 114.
[13]
Ivic M. Etiology of endemic nephropathy [J]. Lijec Vjesn, 1969, 91(12): 1273-1281.
[14]
Ivic M, Lovric B. Carcinogenic action of Aristolochia [J]. Acta Medica Med, 1967, 5: 1-3.
[15]
Schmeiser HH, Bieler CA, Wiessler M, et al. Detection of DNA adducts formed by aristolochic acid in renal tissue from patients with Chinese herbs nephropathy [J]. Cancer Res, 1996, 56(9): 2025-2028.
[16]
Arlt VM, Ferluga D, Stiborova M, et al. Is aristolochic acid a risk factor for Balkan endemic nephropathy-associated urothelial cancer? [J]. Int J Cancer, 2002, 101(5): 500-502.
[17]
Anandagoda N, Lord GM. Preventing aristolochic acid nephropathy [J]. Clin J Am Soc Nephrol, 2015, 10(2): 167-168.
[18]
Toncheva D, Dimitrov T. Genetic predisposition to Balkan endemic nephropathy [J]. Nephron, 1996, 72(4): 564-569.
[19]
Toncheva D, Mihailova-Hristova M, Vazharova R, et al. NGS nominated CELA1, HSPG2, and KCNK5 as candidate genes for predisposition to Balkan endemic nephropathy [J]. Biomed Res Int, 2014, 2014: 920723.
[20]
Staneva R, Rukova B, Hadjidekova S, et al. Whole genome methylation array analysis reveals new aspects in Balkan endemic nephropathy etiology [J]. BMC Nephrol, 2013, 14: 225.
[21]
陈文，谌贻璞. 马兜铃酸肾病的诊断与治疗 [J]. 医师进修杂志，2003，26(5): 11-12.
[22]
Pailer M, Belohlav L, Simonitsch E. The constitution of aristolochic acids [J]. Monatshefte Chem Wissenschaften, 1955, 86(4): 676-680.
[23]
Pailer M, Schleppnik A. Natural herbal substances with a nitro group II: the constitution of aristolochic acid II [J]. Monatshefte Chem Wissenschaften, 1957, 88(3): 367-387.
[24]
Schmeiser HH, Stiborova M, Arlt VM. Chemical and molecular basis of the carcinogenicity of Aristolochia plants [J]. Curr Opin Drug Disc, 2009, 12(1): 141-148.
[25]
Nortier JL, Martinez MC, Schmeiser H, et al. Urothelial carcinoma associated with the use of a Chinese herb (Aristolochia fangchi) [J]. N Engl J Med, 2000, 342(23): 1686-1692.
[26]
Li Y, Liu ZH, Guo XH, et al, Aristolochic acid I-induced DNA damage and cell cycle arrest in renal tubular epithelial cells in vitro [J]. Arch Toxicol, 2006, 80(8): 524-532.
[27]
涂玥，万毅刚，孙伟，等. 马兜铃酸肾毒性的临床特征、分子机制及治疗策略 [J]. 南京中医药大学学报，2018, 34(1): 12-18.
[28]
张良，杨召聪，顾亚琴，等. 马兜铃酸I致大鼠肾损伤后血清miRNA差异表达的研究[J]. 中草药，2016, 47(11): 1903-1907.
[29]
杨召聪，陆茵，顾亚琴，等. 马兜铃酸Ⅰ对大鼠体内PI3K/Akt/NF-кB通路的影响 [J]. 南京中医药大学学报，2015, 31(3): 250-253.
[30]
Zhu SH, Wang Y, Jin J, et al. Endoplasmic reticulum stress mediates aristolochic acid I-induced apoptosis in human renal proximal tubular epithelial cells [J]. Toxico In Vitro, 2012, 26(5): 663-671.
[31]
季文萱，黄俊彦，孟冬梅，等. 马兜铃酸对肾小管上皮细胞氧化应激效应的作用 [J]. 山东医药，2011, 51(25): 98-100.
[32]
国家药典委员会．中国药典[M]. 北京：中国医药科技出版社，2005: 1-846.
[33]
国家药典委员会．中国药典[M]. 北京：中国医药科技出版社，2015: 230-231.
[34]
Zhang LX, Zhang PH, Wang F, et al. Prevalence and factors associated with CKD: a population study from Beijing [J]. Am J Kidney Dis, 2008, 51(3): 373-384.
[35]
Su T, Zhang LX, Li XM, et al. Regular use of nephrotoxic medications is an independent risk factor for chronic kidney disease-results from a Chinese population study [J]. Nephrol Dial Transplant, 2011, 26(6): 1916-1923.
[36]
潘欢欢，张鑫，刘飞，等. 对地方中药材标准中含马兜铃酸类中药的研究 [J]. 中药与临床，2016, 7(3): 5-8.
[37]
杨标，李正红，杨武亮，等. 不同炮制方法对马兜铃中马兜铃酸类物质含量的影响 [J]. 时珍国医国药，2012, 23(10): 2553-2555.
[38]
严建业，王元清，王炜，等. 细辛中马兜铃酸A与黄樟醚的炮制减毒方法研究 [J]. 中草药，2015, 46(2): 216-220.
[39]
殷书梅，王宓，林新艳，等. UPLC法测定复方南星止痛膏中马兜铃酸A的含量 [J]. 南京中医药大学学报，2009, 25(5): 396-397.
[40]
Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease [J]. Kidney Int Suppl, 2013, 3(1): 1-150.
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