马兜铃酸（aristolochic acid，AA）广泛存在于马兜铃科马兜铃属中草药中，是马兜铃酸肾病（aristolochic acid nephropathy，AAN）的致病因素，此类肾病患者可伴发泌尿系统肿瘤，阐明马兜铃酸的致癌机制成为其毒性研究的一大焦点。马兜铃酸Ⅰ（AAⅠ）是马兜铃酸的主要毒性成分，其在体内经氧化还原后活化，与 DNA 共价结合形成加合物而诱发癌变。本文综述参与 AAⅠ氧化还原的代谢酶及其代谢过程在 AAⅠ致癌中的作用。

Aristolochic acid(AA),a major active component of Aristolochiaceae Aristolochia herbs,is the pathogenic factor of aristolochic acid nephropathy(AAN). And AAN patients were usually complicated by urinary cancer. Therefore,the study on the carcinogenesis mechanisms of AA has become the focus in its toxicity research. Recently, researches have demonstrated that aristolochic acidⅠ(AAⅠ)was the main toxic component of AA,and was activated following the oxidation-reduction process. After activation,AAⅠ can induce carcinoma through forming AAⅠ-DNA adducts . This review summarizes the latest research of the enzymes participating in AAⅠ metabolism and their roles in the progress of AA carcinogenesis,which may provide references for follow-up research and its clinical application.

为了降低人工栽培北细辛(Asarum heterotropoides)中的主要毒性成分马兜铃酸A含量,采用田间试验研究了不同遮阴度对3年生北细辛中马兜铃酸A含量的影响。结果表明:在北细辛根适宜采收的8月,50%、70%、90%遮阴度北细辛中马兜铃酸A的平均含量分别为0.256 28mg/g、0.259 88mg/g、0.261 08mg/g,含量差异不显著。同一遮阴度下随着遮阴时间的延长马兜铃酸A含量呈降低趋势,不同遮阴度随着遮阴时间的延长马兜铃酸A含量存在一定差异。综合考虑成本用工等,以50%遮阴度最经济,马兜铃酸A含量也最低。

In order to reduce the content of aristolochic acid A that is the mian toxic components in A.heterotropoides,3 years old A.heterotropoides was covered by different degree of shade by a field trial,to research the effects of different shade levels on the content of aristolochic acid A in A. heterotropoides.The results showed that aristolochic acid A content of A.heterotropoides in the 50%, 70% and 90% shade levels was 0.256 28 mg/g,0.259 88 mg/g,0.261 08 mg/g during the suitable harvest period,respectively.Moreover,they were not significant.The differences of aristolochic acid A content in A.heterotropoides were declined in the same shade level,while the differences of aristolochic acid A content in A.heterotropoides were also different in the different shade level with the extension of time.The effects of 50% shade were the best by considering the cost of labor.

目的研究马兜铃酸肾病（AAN）的临床特点、病理表现，以及影响预后的相关因素。方法回顾性分析我院2006年9月至2012年9月期间住院诊断为马兜铃酸肾病的患者36例，分析各组患者的人口学资料，临床及病理学资料，治疗经过，分析影响患者临床预后的因素。结果马兜铃酸肾病进展隐袭，表现缺乏特异性，部分患者就诊时即有肾功能不全，病理表现为中一重度肾脏小管一间质损害，炎性细胞浸润较少，可见广泛纤维化改变，部分患者在病程中出现恶性肿瘤，预后较差。结论长期服用含有马兜铃酸的药物，可引起马兜铃酸在体内的蓄积，造成肾脏，尤其是肾间质持续不可逆性损害，最终引起肾功能衰竭，也可出现恶性肿瘤。应深入研究马兜铃酸对肾脏损害的机制，寻找有效的治疗手段。

Objective To investigate the clinical and pathological characters of Aristolochic Acid Nephropathy patients. Methods Retrospectively analyze the clinical information and pathological character of 36 Aristolochic Acid Nephropathy patients in the deparment, during Sep 2006 to Sep 2012. Result Aristolochic Acid Nephropathy progress secretly and of non-specific,th renal pathology showed a middle to heavy tubula-interstitial nephrology, with diffuse fibrosis and a small number of inflammatory cell infiltration , malignant tumors arised in urinary system . Conclusion Long-term use of Aristolochic Acid can lead to non-reversible renal injury, and then renal function failure. malignant tumors presented in some patients. It is necessary to investigate the mechanics of Aristolochic Acid Nephropathy, and to seek the effective treatment.

通过研究不同药物配伍中木通的毒性成分马兜铃酸A的含量,考察药物配伍对木通毒性的影响,以指导临床有效地安全用药。方法:通过对龙胆泻肝汤中的药物比例进行调节,将其分为木通组、全处方组、木通+清热组、木通+滋阴组、木通+利水组以及阴性对照组(即全处方除去木通)6组。采用反相高效液相色谱法对各个组别中马兜铃酸A的含量进行测定,比较不同组别间马兜铃酸A的含量差别。结果:通过实验可知,以木通组作为参考组别,全处方组中马兜铃酸A含量最低,木通毒性最小;木通+滋阴组中木通毒性也明显降低;其他组别中马兜铃酸A含量同样较木通组较低,但降低幅度较小。结论:通过实验数据可知,当处方中药物配伍发生变化时,木通的毒性成分含量也随之改变。准确有效的处方配伍可以将木通毒性明显降低,提高药物疗效,减少毒副作用的发生,保证用药的安全性。因此,中药的配伍研究在合理安全用药上具有举足轻重的作用。

Objective:According to study the content of Mutong toxic components aristolochic acid A in different combinations, to observe effects of drug compatibility on toxicity of Mutong, in order to guide safe medication in clinic. Methods:By adjusting the ratio of the Longdan Xiegan decoction, six groups were divided based on proportion of drug, content of aristolochic acid A in six groups were measured by reversed-phase high-performance liquid chromatography. Results: Mutong group as the reference group, content of aristolochic acid A in the full prescribing group was lowest, and the Mutong with minimal toxicity; toxicity of Mutong in Mutong plus Lishui group was obviously lower; in another three groups, it was lower than Mutong group. Conclusion: Toxicity of Mutong changed following the changes of drug compatibility. Reasonable prescription compatibility can reduce toxicity, improve drug efficacy, reduce side effects, ensure the safety of medication. Therefore, the compatibility o

目的优化关木通碱制工艺条件,为其炮制减毒工艺提供参考。方法采用人工神经网络与响应曲面法相结合,分析碳酸氢钠(NaHCO3)溶液、浓度、炮制时间及炮制次数对关木通中马兜铃酸的影响。结果经研究各种影响因素,得到最佳实验条件是NaHCO3浓度0.05 mol·L-1,浸泡3次,浸泡24 h,理论马兜铃总酸去除率可达83.74%。结论径向基人工神经网络与响应曲面法结合为进一步研究关木通的炮制减毒工艺提供了新思路和新方法,具有良好的指导意义。

Objective To optimize the processing conditions of Manchuiran Dutchmanspipe Stem with alkali. Methods The combination of radial basis function ( RBF) and response surface methodology ( RSM) was used to investigate the influence of NaHCO3 , concentration, duration and cycles of processing on the content of aristolochic acid. Results The optimal process was achieved when Manchuiran Dutchmanspipe Stem was soaked for 3 cycles in 0. 05 mol·L-1 NaHCO3 solution, for 24 hours in each cycle. The removal rate of total aristolochic acid approached to 83. 74%. Conclusion The combination of RBF and RSM provided a new method and good guidance for further toxicity attenuation for Manchuiran Dutchmanspipe Stem.