腺嘌呤制作雄性Wistar大鼠肾阳虚型不育症动物模型最佳时效和量效的小样本研究

Construction of the Male Rat Model of Adenine-induced Infertility with Kidney-yang Deficiency

目的:探讨阿拉伯胶助溶后的腺嘌呤对Wistar大鼠生殖毒性的时效和量效关系。方法:将腺嘌呤按0、50、100、150、200mg/ml浓度配制,按与腺嘌呤1:10比例加入阿拉伯胶作为助溶剂,1ml/(100g.d)剂量灌胃,共分5个剂量组;每10d各剂量组处死1批,每组每批5只,共3批。观察大鼠一般状态,分析精子质量、称量体重及生殖器官重量、进行病理检查、用放免法检测性激素的变化,并对腺嘌呤生殖毒性的时效和量效关系进行比较分析。结果:随着腺嘌呤给药时间的延长和剂量的增加,第3d各剂量组肾阳虚体征开始逐渐出现,100mg/(100g.d)剂量组灌胃10d开始,空白对照组比较,精子密度和活力、T、LH水平等各项指标出现明显降低(P<0.05或P<0.01),各给药组睾丸病理均出现轻重不同的病理变化,并呈一定的时效和量效关系。而50mg/(100g.d)剂量组自20d开始出现上述改变。结论:腺嘌呤法制作雄性Wistar大鼠肾阳虚型不育症动物模型最佳剂量点和时间点为按50～100mg/(100g.d)剂量腺嘌呤连续灌胃10～20d。

Objective ： To investigate the time- and dose-related reproductive toxicity of adenine in male Wistar rats. Metheds ： Adenine was dissolved with Arabian sol at the proportion of 1：10 and different adenine solutions were prepared at the concentration of 0, 50, 100, 150 and 200 mg/ml. Seventy-five male Wistar rats were equally assigned to 5 dose groups and received intragastric administration of the adenine solution at 1 ml/（ 100 g · d）. Five from each group were sacrificed every 10, 20 and 30 days, their sperm quality and body and genital weight measured, pathological examinations conducted, sex hormone changes detected by radioimmunoas- say, and analyses made on the time- and dose-related reproductive toxicity of adenine. Results： With the increase in the time and dose of adenine administration, signs of kidney-yang deficiency gradually appeared in all the dose groups on the third day; and statistically significant changes were observed in sperm concentration and motility, and serum testosterone and luteinizing hormone levels in the 100 mg/（ 100 g · d） group （P 〈 0.05 or P 〈 0.01 ） by the 10th day. The same changes were observed in 50 mg/（ 100 g·d） group by the 20th day. Different degrees of pathological changes were noted in a time and dose-dependent manner in all the dose groups, suggestive of a progressive reduction of the reproductive function with the increase of time and dose of adenine administration. Conclusion .. For the construction of the male rat model of adenine-induced infertility with kidney-yang deficiency, the best dose is 50- 100 mg/（ 100 g · d） and the best administration time is 10-20 consecutive days intragastrically.