雷公藤内酯醇对雄性大鼠的生殖毒性及其机制研究

Reproductive toxicity of triptolide and its mechanism in male rats

评价雷公藤内酯醇的雄性生殖毒性,观察染毒后雄性大鼠精子的畸形率、睾丸组织脂质过氧化物、睾丸组织标志酶活力和血清中激素水平的改变。设阴性和阳性对照组,以低(0.025 mg·kg^(-1))、中(0.05 mg·kg^(-1))、高剂量(0.1 mg·kg^(-1))的雷公藤内酯醇混悬液对健康雄性Wistar大鼠连续灌胃染毒30 d,1次/d,于末次染毒24 h后处死大鼠,测定睾丸组织和血清中各项指标,并考察附睾精子畸形率。结果显示阳性对照组相比阴性对照组,各组具有显著性差异。中剂量染毒组的大鼠睾丸组织SOD,LDH,G-6-PD,Na+-K+-ATPase,Ca+-Mg+-ATPase含量较阴性对照组显著降低,并随着染毒达到高剂量,以上各指标的下调更加明显。大鼠睾丸组织GSH-Px和β-G水平只在染毒高剂量时,表现出明显的下降。而各染毒组的MDA,FSH,LH水平均表现差异无统计学意义。雷公藤内酯醇染毒中、高剂量组精子畸形率高于阴性对照组。提示在该实验染毒和剂量范围内,雷公藤内酯醇对睾丸组织具有脂质过氧化作用,导致生精细胞、支持细胞和间质细胞的损伤;同时伴有睾丸标志酶活力的下降,阻碍睾丸组织的有氧代谢和细胞对能量的利用,形成了一条对雄性生殖系统的损伤链。

The arrenotokous toxicity of triptolide was evaluated,and the rate of sperm abnormality,the changes of the lipid peroxide,the enzyme activity and the hormone in male rats were observed. With the negative and positive control group,the healthily male rats were respectively given by gavage triptolide suspension at the dose of 0. 025,0. 05,0. 1 mg·kg^（-1） for 30 days. Then the rats were killed for the measurement of the indicators in testis and serum,as well as the study on the sperm abnormality. The results showed that the positive control group had significant difference,compared with the negative control group. The content of SOD,LDH,G-6-PD,Na＋-K＋-ATPase,Ca＋-Mg＋-ATPase decreased significantly in 0. 05 mg·kg^（-1） group,and reduced more obviously with exposure to the dose of 0. 1 mg·kg^（-1）. The levels of GSH-Px and β-G showed a significant decrease in the testis of rats only at the dose of 0. 1 mg·kg^（-1）. Nevertheless,the MDA levels,the FSH levels and the LH levels showed no significant difference. The deformity rate of sperm increased significantly in 0. 05 mg·kg^（-1） group and 0. 1 mg·kg^（-1） group. The results indicated the triptolide had the effect of the lipid peroxidation to damage Spermatogenic cells,Sertoli＇s cells and Leydig cells. At the same time,the triptolide interfered not only with the energy supply process of aerobic and anaerobic glycolysis,but also with the energy utilization in testis by affecting the activities of testis marker enzymes,and produced a damage chain of the male reproductive system.