核磁共振技术结合模式识别对中药马兜铃酸亚急性生化效应的研究

Studies on Subacute Biochemical Effects of Aristolochic Acid Using 1H NMR Spectroscopy Combined with Pattern Recognition

利用核磁共振技术结合模式识别方法,研究了马兜铃酸(AristolochicAcid,AA)的亚急性生化效应.大鼠连续5日腹腔注射马兜铃酸后,不同时间段尿液1HNMR谱显示与肾小管及肾乳头受损相关的标记物(NMRmarker)浓度有显著变化;铬酸钠、氯化汞、二溴乙胺、盐酸肼和异硫氰酸-α-萘酯,并利用主成分分析法对造成的肝肾损伤模型组、AA组和对照组的大鼠尿液1HNMR谱解析和分类.1HNMR谱中各种代谢物的谱峰强度变化及主成分分析结果均显示,马兜铃酸引起的肾损伤与肾小管及肾乳头损伤模型类似,且随给药量的积累,肾损伤范围扩大程度加深,引起肾脏不可逆损伤.该方法可用于中药的毒理学研究.

1H NMR spectroscopy and pattern recognition method were used to the studies on the subacute biochemical effects of aristolochic acid(AA). Male Wistar rats were intraperitoneal with AA for 5 days. Urine samples were collected after being treated with AA and the NMR spectra show the NMR marker related to renal papillary and proximal tubular lesion changed greatly. Urine samples from the rats treated with model toxins sodium chromate, mercury Ⅱ chloride, 2-bromoethanamine hydrobromide, α-naphthylisothiocyanate and hydrazine(NaCrO_4, HgCl_2, BEA, ANIT and HYD) were collected over a 48 h time course. Each NMR spectrum was data-processed and analyzed by PCA methods. A successful classification of the toxicity and biochemical effects of AA was achieved. The biochemical effects and PCA classification indicate that the renal toxicity of AA was a progressive course with the accumulation of AA, and caused widespread lesion to kidney including proximal tubule and papillary necrosis. The lesion is irreversible. This method can be used in the toxicological study of other drugs.