卡马西平对健康及癫雄性大鼠生殖系统相关指标的影响

Effects of reproductive system in experimental male rats with carbamazepine

目的探讨卡马西平单药以及癫与卡马西平共同作用下对雄性大鼠生殖系统相关指标的影响,为癫男性患者临床用药提供基础研究数据。方法运用氯化锂-匹罗卡品建立Wistar雄性大鼠癫模型。选择健康清洁的Wistar雄性大鼠设造模组、非造模组及对照组,再将造模组、非造模组随机分为三个亚组,分别给予不同浓度卡马西平灌胃60 d后,所有入组大鼠取血样、睾丸、附睾、精子标本,分别观测血清性激素[(总睾酮(TT)、雌二醇(E2)、孕酮(P)、泌乳素(PRL)、黄体生成素(LH)、卵泡刺激素(FSH)]、脏器系数、精子计数、精子活力与形态等指标,分析卡马西平单药及癫与卡马西平协同作用对雄性大鼠生殖的影响。结果造模组大鼠给予不同浓度卡马西平灌胃后,LH、FSH、E2水平均较对照组明显升高(P均<0.01),各浓度组P水平均明显低于对照组(P均<0.05),各浓度组TT水平明显低于对照组,PRL水平未见明显改变。非造模组大鼠给予不同浓度卡马西平药物灌胃后,LH、FSH水平均较对照组明显升高(P均<0.01),TT水平均低于对照组(P均<0.05),PRL水平中高浓度组明显低于对照组(P均<0.05),P、E2未见明显改变。非造模组大鼠给予不同浓度卡马西平药物灌胃后,各浓度组附睾重量及附睾脏器系数均较对照组明显降低(P均<0.01)。结论卡马西平对于雄性大鼠生殖系统相关指标存在明显不良反应,且有明显药物浓度关联性,而卡马西平与癫发作共同作用的不良反应未见协同叠加效应。

Objective To study the effects of CBZ and CBZ with epilepsy on reproductive system of male Wistar rats. Methods Male rat epilepsy models were established with lithium-pilocarpine and health male Wistar rats controls were used. They were given three different concentration carbamazepine infused into stomach. Blood,testis and epididymis,and sperms were sampled; serum sex hormones,viscera coefficient,sperm counts,sperm motility and morphology were observed for analyzing on effects male epileptrc rats＇ reproductive system. Results In the epilepsy model rats receiving high,medium and low concentration CBZ showed that LH,FSH,E2 were significantly higher than in controls,there were but no significant differences between the three concentration groups.Progesterone（ P） levels of three concentrations were obviously lower than in controls,but in low concentration group was significantly lower than in the other two concentration groups. Testosterone（ T） levels in three concentration groups were significantly lower than in healthy group. No changes were found in PRL. In the health control Wistar rats receiving. high,medium and low concentration CBZ,LH and FSH were significantly higher than in controls,testosterone（ T） levels in three concentration groups were significantly lower than in health group,especially the high concentration group,PRL levels in medium and low concentration group obviously lower than in controls. There was no difference in P and E2. There were no changes in weight and testicular weight and testicular viscera coefficient between male epilepsy rats and health group,but epididymis weight and epididymis viscera coefficient were obviously lower in the health rats with three concentration CBZ than in controls. No sperm count change in the three concentrations for male epilepsy rats and health group,but both of them had the lower sperm activity rate than in controls,especially in high concentration group. Conclusions Carbamazepine itself for male rats reproductive system has obvious side effects and obvious drug concentration relevance,both carbamazepine and epilepsy also present the part of the side effects of correlation concentration,but the mechanism is relatively complex,caused by many factors in joint action.