大鼠肾炎灵片长期毒性试验及对雄性性腺功能的影响

Long-Term Toxicity of Shen Yan Ling Tablet and Its Effect on Male Reproductive Function in Rats

目的:中药益肾清利复方肾炎灵片是雷公藤、生黄芪等复方配伍剂,既对肾小球疾病有确切临床疗效,又减轻了雷公藤的不良反应。按照《新药(西药)临床前毒理学研究指导原则》的规范,研究中药肾炎灵片对大鼠长期毒性,及对雄性性腺功能的影响。方法:根据临床治疗剂量和急性毒性试验结果,设定了肾炎灵低剂量(1.25g/kg体重)、中剂量(2.50g/kg体重)、高剂量(5.00g/kg体重)和对照组,每组20只,雌雄各半,给予大鼠连续灌服肾炎灵干粉3个月,进行规范化的长期毒性试验,同时观察肾炎灵对血清性激素和附睾精子计数的影响。结果:连续给药3个月,动物无死亡,一般情况良好。血液学和生物化学检查的各项指标绝大部分在正常范围内波动,与对照组比较,试验组个别指标有统计学意义的变化(如RBC、WBC、HGB、AST、TBIL,P<0.05),但没有临床意义。主要脏器质量系数与对照组无显著性差异,组织学检查发现,高剂量组部分大鼠肝、肺有轻度病理改变。血清激素水平变化不显著(P>0.05),高剂量组附睾管腔内精子数量减少(P<0.05)。结论:该剂量范围(1.25～5.00g/kg体重)肾炎灵灌喂大鼠3个月,不产生明显的积蓄性毒性反应;较大剂量(≥5.00g/kg体重)对雄性性腺产生负性影响。

Objective： Shen Yan Ling Tablet is an innovative compound of traditional Chinese medicine, scientifically prepared with Tripterygium wilfordii, Radix Astragali, and others, with precise efficacy on renal diseases and reduced adverse effects of Tripterygium wilfordii. Based on the Guiding Principles for New Drug Toxicity Research Before Clinical Application, we investigated the long-term toxicity of Shen Yan Ling Tablet and its effect on the reproductive function in rats. Methods ： According to the clinical therapeutic dose and the results of the acute toxicity test of Shen Yah Ling Tablet, we equally divided 80 rats （ males and females half-and-half） into a low-dose （1.25 g/kg body wt）, a medium-dose （2.50 g/kg body wt）, a high-dose （5.00 g/kg body wt） and a control group. After a 3-month medication, we conducted standardized long-term toxicity tests and observed the effects of Shen Yah Ling on the serum sexual hormones and epididymal sperm count. Results ： After 3 months of treatment with Shen Yah Ling, no death occurred, the general status remained unchanged, and the parameters of blood cytology and biochemistry fluctuated within the normal range, without any significant changes （P 〉 0.05）. Some blood parameters, RBC, WBC, HGB, AST and TBIL, showed statistic changes （P 〈 0.05）, but with no clinical significance. There were no significant differences in the mass coefficients of the main organs between the medica-tion and control groups. The high-dose group exhibited slight hepatic and pulmonary pathological changes and significantly reduced sperm counts in the epididymis, but no significant changes in serum sexual hormones （ P 〈 0.05 ）. Conclusion ： Three-month medi- cation of Shen Yah Ling at 1.25 - 5. 00 g/kg produced no significant accumulated toxicity on rats, but it had a negative effect on their reproductive function at a higher dose of ≥ 5.00 g/kg.