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目的探讨新型雷公藤甲素衍生物MC004对大鼠睾丸组织结构及睾丸酶活力的影响。方法雄性Wistar大鼠32只,随机分为4组。隔日尾静脉注射,溶剂对照组和低、中、高剂量组分别给予生理盐水和0.25、0.50、0.75 mg/kg的MC004,共28 d。末次给药24 h后剖杀,制备睾丸病理切片并测定睾丸中乳酸脱氢酶(LDH)、乳酸脱氢酶x(LDH-x)、酸性磷酸酶(ACP)和山梨醇脱氢酶(SDH)的活力。结果与对照组相比较,MC004 0.75 mg/kg组大鼠体重增长缓慢;各剂量组睾丸、附睾的绝对重量及相对重量均显著降低(P<0.01);MC004可引起大鼠睾丸组织匀浆中LDH、LDH-x、SDH和ACP酶活力的显著降低,差异均有统计学意义(P<0.01)。结论雄性大鼠隔日尾静脉注射给药28 d 0.25 mg/kg剂量的MC004时,即能引起大鼠睾丸组织病理学改变且对睾丸酶活力具有显著抑制作用,从而产生雄性生殖毒性。
Objective To investigate the effects of a new triptolide derivative MC004 on rat testicular tissue structure and testicular enzyme activity. Methods Thirty-two male Wistar rats were randomly divided into 4 groups. After intravenous injection every other day, the vehicle control group and the low, middle, and high dose groups were given physiological saline and MC004 0.25, 0.50, 0.75 mg/kg, respectively, for a total of 28 days. After 24 hours after the last dose, the testis was cut to prepare testicular pathological sections and testicular lactate dehydrogenase (LDH), lactate dehydrogenase x (LDH-x), acid phosphatase (ACP), and sorbitol dehydrogenase (SDH) were determined. ) The vitality. Results Compared with the control group, the weight gain of rats in the MC004 0.75 mg/kg group was slow; the absolute weight and relative weight of the testis and epididymis in each dose group were significantly decreased (P<0.01); MC004 can cause rat testicular tissue homogenization. The activities of LDH, LDH-x, SDH and ACP were significantly decreased, and the differences were statistically significant (P<0.01). Conclusions The administration of MC004 at a dose of 0.25 mg/kg for 28 days to the male rats every other day can induce the pathological changes of the testes of the rats and have a significant inhibitory effect on the testicular enzyme activity, resulting in male reproductive toxicity.