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目的探讨抗癫痫药物对Wistar大鼠性激素分泌以及卵巢生成卵泡和黄体的影响。方法健康雌性Wistar大鼠60只,随机分为对照组、丙戊酸钠组、奥卡西平组、左乙拉西坦组、左乙拉西坦+奥卡西平组以及左乙拉西坦+丙戊酸钠组,每组10只。按照分组每天给药2次,连续3个月,处死前1个月,每天阴道涂片3次(6:00,14:00,20:00),判定动物的性周期阶段,在动情间期采血、处死,并分离卵巢组织。卵巢称重;卵巢组织采用HE染色并观察卵泡和黄体数目;采用放免法测定血中雌二醇、孕酮水平。结果与对照组比较,左乙拉西坦+奥卡西平组孕酮水平上升(P<0.01);丙戊酸钠组、奥卡西平组、左乙拉西坦组、左乙拉西坦+丙戊酸钠组孕酮水平下降(P<0.01),同时,左乙拉西坦组雌二醇水平下降(P<0.01);左乙拉西坦+奥卡西平组黄体数目增加(P<0.05),左乙拉西坦+奥卡西平组、左乙拉西坦+丙戊酸钠组卵泡数目下降(P<0.01)。结论长期应用抗癫痫药物可以引起性激素分泌紊乱,对于女性癫痫患者,应根据不同时期的发育特点选择用药。
Objective To investigate the effects of antiepileptic drugs on the secretion of sex hormones and ovarian follicles and corpus luteum in Wistar rats. Methods Sixty healthy female Wistar rats were randomly divided into control group, sodium valproate group, oxcarbazepine group, levetiracetam group, levetiracetam + oxcarbazepine group and levetiracetam + Sodium valproate group, each group of 10. According to the sub-group administered 2 times a day for 3 consecutive months, 1 month before the death, vaginal smear 3 times a day (6:00, 14:00, 20:00), to determine the animal’s sexual cycle stage, during the estrus period Blood was collected, sacrificed, and ovarian tissue was isolated. The ovary was weighed. The ovarian tissue was stained with hematoxylin and eosin (HE) to observe the number of follicles and corpora lutea. The level of estradiol and progesterone in blood was determined by radioimmunoassay. Results Compared with the control group, the levels of progesterone in levetiracetam + oxcarbazepine group were significantly increased (P <0.01), while those in sodium valproate group, oxcarbazepine group, levetiracetam group, levetiracetam + The progesterone level in sodium valproate group decreased (P <0.01), while the estradiol level in levetiracetam group decreased (P <0.01); the number of luteal phase in levetiracetam + oxcarbazepine group increased (P < 0.05). The number of follicles in levetiracetam + oxcarbazepine group and levetiracetam + sodium valproate group decreased (P <0.01). Conclusion Long-term use of antiepileptic drugs can cause sexual hormone secretion disorders, for women with epilepsy, should be based on different periods of development characteristics of choice medication.