基于Ⅱ型胶原诱导性关节炎模型大鼠探讨雷公藤多苷片的长期毒性研究

Study on long-term toxicity of Tripterygium glycosides tablets based on typeⅡcollagen-induced arthritis model rats

目的观察雷公藤多苷片对Ⅱ型胶原诱导性关节炎(CIA)大鼠多系统的毒性反应。方法将健康SD大鼠随机分为正常组、模型组及实验组,每组10只;除正常组外,其余各组建立胶原诱导性关节炎模型。首次免疫后灌胃给药,正常组和模型组均给予等体积0.3%羧甲基纤维素钠溶液,实验组给予72 mg·kg^(-1)·d^(-1)雷公藤多苷溶液,每天给药1次,连续给药6周。于第42天取材,各组分别检测血常规,计算脏器指数;用酶联免疫吸附试验法检测大鼠肝、肾功能及性激素等水平;用苏木精-伊红(HE)染色法观察肝、肾、卵巢、睾丸组织病理形态学改变。结果正常组、模型组和实验组的睾丸指数分别为(0.81±0.05)%、(0.97±0.06)%和(0.81±0.12)%,雌二醇含量分别为(63.90±16.19)、(55.42±7.23)和(40.04±5.97)pg·mL^(-1),睾酮含量分别为(1290.96±257.94)、(1198.43±190.77)和(912.62±61.72)pg·mL^(-1)。模型组的上述指标与实验组比较,在统计学上差异均有统计学意义(P<0.01,P<0.05)。HE病理结果表明,雷公藤多苷片能引起CIA模型大鼠的卵巢、睾丸组织病理学异常改变。结论雷公藤多苷片8倍临床等效剂量连续用药6周可以引起CIA大鼠生殖系统的损伤。

Objective To observe the multi-system toxicity of Tripterygium glycosides tablets in rats with typeⅡcollagen-induced arthritis(CIA).Methods Healthy SD rats were randomly divided into normal group,model group and experimental group,with 10 rats in each group.In addition to the normal group,the other groups were established collagen-induced arthritis model.After the first immunization,the normal group and the model group were given an equal volume of 0.3%sodium carboxymethyl cellulose solution,and the experimental group was given 72 mg·kg^(-1)·d^(-1)Tripterygium glycosides solution,once a day for 6 weeks.On the 42 nd day,the blood routine of each group was detected and the organ index was calculated.The levels of liver,kidney function and sex hormones in rats were detected by enzyme-linked immunosorbent assay.The histopathological changes of liver,kidney,ovary and testis were observed by hematoxylin-eosin(HE)staining.Results The testicular indexes of the normal group,the model group and the experimental group were(0.81±0.05)%,(0.97±0.06)%and(0.81±0.12)%;the estradiol contents were(63.90±16.19),(55.42±7.23)and(40.04±5.97)pg·mL^(-1);the testosterone contents were(1290.96±257.94),(1198.43±190.77)and(912.62±61.72)pg·mL^(-1),respectively.There were statistically significant differences in the above indexes between the model group and the experimental group(P<0.01,P<0.05).HE pathological results showed that Tripterygium glycosides tablets could cause abnormal histopathological changes of ovary and testis in CIA model rats.Conclusion Continuous administration of 8-fold clinical equivalent dose of Tripterygium glycosides tablets for 6 weeks can cause damage to the reproductive system of CIA rats.