摘要
目的探讨不同剂量马兜铃酸对大鼠肾脏功能和组织形态学的影响。方法制备关木通浸膏剂，并测定其中马兜铃酸（AA）的含量。取36只雄性Wistar大鼠随机分为4组，实验组分为低剂量组（AA5mg·kg^-1·d^-1）、中剂量组（AA 10mg·kg^-1·d^-1）、高剂量组（AA20mg·kg^-1·d^-1），用不同剂量的关木通浸膏灌胃；对照组用同体积饮用水灌胃。各组每周测量体重，于第8周留取24h尿液；腹主动脉采血，测定相关肾功能指标；取肾组织进行形态学检查。结果用药后各组尿量均明显增多，体重明显降低，且以中、高剂量组体重下降最明显；低剂量组尿蛋白、尿N-乙酰-D氨基葡萄糖酶（NAG）排泄量，以及肌酐、尿素氮与正常对照组比较，差异无统计学意义，而中、高剂量组尿蛋白、尿酶排泄量明显升高。肾脏组织形态学观察，低剂量组肾脏损害轻微，中、高剂量组表现为不同程度的肾小管损伤、坏死和小管灶性萎缩以及早期间质纤维化，其中以高剂量组病变较严重。电镜观察高剂量组肾小管上皮细胞超微结构发生显著变化，主要是细胞核变异。结论马兜铃酸肾毒性是相对的，与用药剂量有关。
Objective To study the effect of different dose of Aristolochic acid （AA） on renal function and pathological changes of rats. Method 36 Wistar male rat were randomly divided into 4 groups. Experimental groups were given AA intragastically, respectively treated by low-dosage （AA5mg/kg· d）, middle dosage（AA10mg/kg· d）, and high dosage（AA20mg/kg· d）, the normal group by equal volume of potable water. The body weight were taken weekly. At the end of 8th weeks, collected 24h-urine, the blood samples were taken from abdominal aorfa for detection of parameters for renal functions. The renal tissues were taken for morphological detection. Results After given AA, the urinary excretion increased, with decrease of body weight in every group, whereas much more obviously in the middle dosage and high dosage groups. Compared with the normal group, the urinary excretion of albumin and NAG enzyme, the level of serum creatinine and BUN had no difference in the low dosage group, but increased in the middle dosage and high dosage groups. The renal pathological changes were slight in the small dosage group, but in the groups of middle dosage and high dosage. Renal tubular injury, necrosis, focal atrophy, and early interstitial fibrosis were demonstrated, which were more seriously in the group of AA20mg.·kg^-1· d^-1. The ultramicroscopic structure of renal tubulo-epithelial cells observed by electron-microscope showed that there were obvious changs in high dosage group, mainly nuclear abnormality. Conclusions The renal toxicity of aris tolochic acid was relative, and dose dependent.
出处
《临床肾脏病杂志》
2005年第6期261-264,F0003,共5页
Journal Of Clinical Nephrology
基金
上海市自然科学基金资助课题（NQ03ZR14031）
关键词
马兜铃酸
毒性试验
肾疾病
Aristolochic acid
Toxicity test
Kidney diseases
