含马兜铃酸的中药临床应用状况分析

目的通过临床对含马兜铃酸的中药使用情况进行分析,研究含马兜铃酸的中药使用临床应用情况以及对马兜铃酸肾病的认识情况。方法通过临床对中药细辛、威灵仙、川木桶、汉防己等药物的使用量比较含马兜铃酸药物的临床使用情况。并且对医院的医师进行含马兜铃酸药物组成的认识与使用情况进行问卷调查,同时也对马兜铃酸肾病的情况知晓程度进行研究,分析含马兜铃酸的中药临床应用状况。结果通过医院临床使用药物的调查以及对医师使用含马兜铃酸的中药进行问卷调查发现,含马兜铃酸的药物使用量一直呈上升的趋势,但是马兜铃酸肾病并没有受到医师的重视。结论随着含马兜铃酸的中药的大量使用,临床也要对药物所产生的毒副作用进行重视,要加强对马兜铃酸肾病的研究,培养医师对药物毒副作用的认识。     

中药马兜铃酸的研究进展

本文总结了马兜铃酸的化学结构、含马兜铃酸的中草药及中成药、马兜铃酸的药理作用和毒性作用、马兜铃酸肾病。通过本文的综述,使医药人员对马兜铃酸有一个全面、正确的认识,以指导临床安全、合理、规范使用含有马兜铃酸的中药。     

从马兜铃酸致肾损害谈如何避免中药不良反应

目的：就如何避免中药不良反应进行探讨。方法：以马兜铃酸以及舍马兜铃酸的中药材为个案，对相关信息进行归纳、分析。结果：提出了避免中药不良反应的8项建议。结论：避免中药不良反应的发生，关键在于科学合理使用中药。     

警惕含马兜铃酸中药引起肾脏损害

根据近年来关于含马兜铃酸中药引起肾脏毒性的不良反应报道增多,提出使用此类药品的注意事项以及有关药品监督管理方面的建议等,以期对此类药品的不良反应予以重视并加强管理。     

含马兜铃酸的药物临床应用分析

本文对基层使用含马兜铃酸的中药的使用情况做一总结研究,以了解基层医院的医生对此类药物的临床使用及对马兜铃肾病的认识情况,从而提出如何加强新理论、新知识在基层医生中的推广和学习.     

含马兜铃酸成分的中药及中成药的合理应用

药物是防病治病的有力武器。但它具有二重性 ,一方面应用得当 ,可以根除病因 ,解除病人的疾苦 ;另一方面 ,若应用不当 ,就会出现不良反应 ,甚至造成严重后果或死亡。 2 0 0 1年 6月 2 0日 ,美国食品与药品管理局 (FDA)发布公告 ,要求在全美国范围内收回已售出的 1 3种中成药 ,并警告全国消费者不要继续使用关木通、马兜铃、八正散、当归四逆汤等含有马兜铃酸成分的中药材及中成药 ,因为该成分对消费者的健康造成损伤。国内多家媒体转载了这一消息 ,一时中医药在美国的境遇再度引起国人的高度关注。近来有关服用含“马兜铃酸”成分的中药及…     

哪些中药含有马兜铃酸

20世纪90年代后,国内外陆续发现,广防己、关木通、青木香等中药饮片及其中成药制剂中所含的马兜铃酸成分可导致。肾损害,甚至可致泌尿系统肿瘤。其中,短期大剂量使用会导致急性肾损伤,长期小剂量使用可导致慢性肾损害,肾功能本身受损或异常者使用含马兜铃酸的药物更易受损害。     

马兜铃酸与肾毒性

媒体报道了龙胆泻肝丸可能导致肾损害的消息,引起公众对用药安全的关注.     

含马兜铃酸植物药的毒性概述

马兜铃酸( Aristolochic acid)是关木通、广防己、马兜铃、天仙藤、青木香、寻骨风和朱砂莲以及铁线莲马兜铃、蛇根马兜铃、印度马兜铃等 10余种马兜铃科马兜铃属植物药中的一类菲类化合物,主要由马兜铃酸 A、 B、 C、 D、 E等及其衍生物组成.近年来,随着因服用含马兜铃酸的植物药导致肾损害的报道不断出现,人们对马兜铃酸的毒性越发关注.     

马兜铃酸肾病的临床病理分析

目的 探讨马兜铃酸肾病的临床病理特点。方法 回顾性分析3例马兜铃酸肾病患者的临床表现及病理资料。结果 2例急性马兜铃酸肾病临床表现为：消化道症状、肾功能减退、尿酶升高、电解质紊乱;病理诊断为急性肾小管坏死。1例慢性马兜铃酸肾病临床表现为：贫血、尿检异常、高血压、肾功能减退,病理诊断为慢性间质性肾炎。结论 含有马兜铃酸的中药有肾损害,可致马兜铃酸肾病,其临床表现病理变化有一定特点。     

The carcinogenic action of aristolochic acid in rats

Male and female Wistar rats treated orally with 0.1, 1.0 or 10.0 mg/kg/day aristolochic acid as its sodium salt (AA) developed a high incidence of tumours dependent on dose and time. After 3 months' treatment 1.0 and 10.0 mg/kg AA led to severe papillomatosis of the forestomach with occasional signs of malignancy. Three to 6 months later without further treatment the rats developed squamous cell carcinomas in the forestomach with formation of metastases. At the same time anaplasia of the tubular epithelium and mainly adenomas appeared in the renal cortex. The transitional epithelium of the renal pelvis and the urinary bladder showed hyperplasia, papillomas or carcinomas. For the low dose (0.1 mg/kg) the treatment with AA varied between 3 and 12 months. No tumours were observed in the first 6 months of the study. After 12 and 16 months, however, papillomas or squamous cell carcinomas also occurred in the forestomach. In addition, hyperplasia of the transitional epithelium of the renal pelvis was found while the renal cortex and the urinary bladder remained normal.This paper was presented in part at the 23rd Annual Meeting of the European Society of Toxicology, March 21–24, 1982, Tel Aviv, Israel     

Short-term toxicity of aristolochic acid, aristolochic acid-I and aristolochic acid-II in rats.

We compared the short-term toxicity of toxic components of aristolochic acid in rats. Twenty-four female Wistar rats were divided into 4 groups and treated orally every 3-days with 10 mg/kg each of aristolochic acid, aristolochic acid-I and aristolochic acid-II for 19 days. After treatment, the relative ratio of liver and kidney weight to body weight, the concentrations of RBC, hemoglobin and hematocrit in the blood, the levels of aspartate amino transferase, alanine amino transferase, alkaline phosphatase, blood urea nitrogen and creatinine in the plasma, and the levels of urinary urea nitrogen and creatinine in the urine were significantly increased. Body weight of rats and the levels of Na(+), K(+), Ca(2+) in the urine were significantly decreased, especially for groups treated with aristolochic acid and aristolochic acid-II. Pathological examination of liver and kidney also showed cell enlargement and lesions, especially for groups treated with aristolochic acid and aristolochic acid-II. The aristolochic acid exhibited significant toxicity, and the short-term toxicity of aristolochic acid-II and aristolochic acid was similar to each other. Renal but not hepatic failure induced by aristolochic acid could be prevented by pentoxifylline.     

Acute toxicity of aristolochic acid in rodents

The acute toxic effects of aristolochic acid (AA) were tested in rats and mice of both sexes. Oral or intravenous administration in high doses was followed by death from acute renal failure within 15 days. Histologically, the predominant features were severe necrosis affecting the renal tubules, atrophy of the lymphatic organs and large areas of superficial ulceration in the forestomach, followed by hyperplasia and hyperkeratosis of the squamous epithelium. The LD₅₀ ranged from 56 to 203 mg/kg orally or 38 to 83 mg/kg intravenously, depending on species and sex.Dedicated to Dr. Rolf Madaus on the occasion of his 65th birthday.     

HPLC法测定单叶细辛中马兜铃酸A的含量

目的 HPLC法测定单叶细辛中马兜铃酸A的含量。方法采用Sunfire C18柱(150mm×4.6mm,5μm);流动相:甲醇-水-醋酸(60∶36∶4);检测波长316nm。结果线性范围为6.60~39.60μg.mL-1(r=0.9995),平均回收率为95.8%,RSD为0.8%(n=6)。结论该方法简便、准确,可用于单叶细辛中马兜铃酸A的质量控制。     

Tumour induction in mice following exposure to aristolochic acid

After treatment for 3 weeks with aristolochic acid (AA) in daily doses of 5.0 mg/kg mice were kept under observation for approximately 1 year. During this period papillomatous changes occurred in the forestomach. At a later stage, squamous cell carcinomas were observed in all the animals. In one case, an adenocarcinoma was found in the glandular stomach. In addition, malignant lymphomas were found, as well as adenomas of the kidneys, carcinomas of the lungs, and haemangiomas of the uteri.This is a short report on the experiments conducted. All results are available from the author on request     

北马兜铃的化学成分研究——Ⅱ、马兜铃酸E的化学结构

From the root of Aristolochia contorta Bunge six chemical constituents were isolated; one of them is a new phenanthrene compound containing nitro group for which the name aristolochic acid E is suggested. By means of spectral methods combined with chemical analysis the chemical structure of aristolochic acid E was determined to be 7-methoxy-8-hydroxy-aristolochic acid. The other components were identified as allantoin, aristolochic acid A, magnoflorine, β-sitosterol and daucosterol respectively.     

Developmental nephrotoxicity of aristolochic acid in a zebrafish model

Aristolochic acid (AA) is a component of Aristolochia plant extracts which is used as a treatment for different pathologies and their toxicological effects have not been sufficiently studied. The aim of this study was to evaluate AA-induced nephrotoxicity in zebrafish embryos. After soaking zebrafish embryos in AA, the embryos displayed malformed kidney phenotypes, such as curved, cystic pronephric tubes, pronephric ducts, and cases of atrophic glomeruli. The percentages of embryos with malformed kidney phenotypes increased as the exposure dosages of AA increased. Furthermore, AA-treated embryos exhibited significantly reduced glomerular filtration rates (GFRs) in comparison with mock-control littermates (mock-control: 100 ± 2.24% vs. 10 ppm AA treatment for 3-5 h: 71.48 ± 18.84% ~ 39.41 ± 15.88%), indicating that AA treatment not only caused morphological kidney changes but also induced renal failure. In addition to kidney malformations, AA-treated zebrafish embryos also exhibited deformed hearts, swollen pericardiums, impaired blood circulation and the accumulation(s) of red blood cells. Whole-mount in situ hybridization studies using cmlc2 and wt1b as riboprobes indicated that the kidney is more sensitive than the heart to AA damage. Real-time PCR showed that AA can up-regulate the expression of proinflammatory genes like TNFα, cox2 and mpo. These results support the following conclusions: (1) AA-induced renal failure is mediated by inflammation, which causes circulation dysfunction followed by serious heart malformation; and (2) the kidney is more sensitive than the heart to AA injury.     

马兜铃酸致DNA损伤的体外研究

目的研究马兜铃酸(AA)体外致DNA损伤作用。方法采用噻唑蓝比色法比较AA对人胚肾293细胞与转染核苷酸切除修复基因的ERCC1-XPF-293细胞毒性差异;采用单细胞凝胶电泳试验研究AA致293细胞DNA单链断裂作用;以EB荧光法研究AA致牛胸腺DNA交联作用及其代谢活化。结果AA对人胚肾293细胞及ERCC1-XPF-293细胞的半数抑制浓度分别为480.1和661.8μmol/L(P<0.05);AA在60μmol/L即具有致DNA单链断裂作用;加大鼠肝S9条件下AA致牛胸腺DNA交联,同时加入CYP1A抑制剂α-萘黄酮降低DNA交联率。结论AA所致DNA损伤作用是其细胞毒性的重要机制之一。     

马兜铃酸毒理学性研究与启示

有关马兜铃酸的毒理实验国内外均有报道,尤其国外在毒理学方面做了大量研究.大量的实验提示:马兜铃酸的肾毒性与剂量呈相关性;遗传毒性研究提示马兜铃酸具有致突变作用;在对大鼠和小鼠的长期毒性研究中发现:动物可发生局部和全身肿瘤,且肿瘤的发生与给药时间和剂量呈相关性;并发现动物的主要毒性与人的不良反应有相关性.马兜铃酸的相关实验研究提醒有关方面应重视马兜铃酸问题,使传统中药更好地发挥防病治病作用.