更舒方对去势围绝经期综合征模型大鼠的药效学研究

Pharmacodynamic Study of Gengshufang(更舒方) on Castrated Perimenopausal Syndrome Model Rats

目的:观察更舒方对卵巢去势围绝经期综合征模型大鼠行为学特点、血清激素及子宫系数的影响,探讨更舒方针对围绝经期综合征的药效学特点。方法:采取卵巢去势法制备围绝经期综合征大鼠模型。将造模成功48只大鼠据体质量按随机区划法分为模型组、坤泰组、17-β雌二醇+孕酮(下称雌激素组)以及更舒方高、中、低剂量组,同时设假手术组作为对照组。雌激素组皮下注射给药,其余组灌胃给药,给药4周,于末次给药后24 h内进行旷场实验、高架十字迷宫实验及明暗箱实验,进行行为学评估;采用10%水合氯醛(30 mg/kg)腹腔麻醉后腹主动脉取血并切除子宫;采用ELISA法测定血清雌二醇(E2)、促黄体生成素(LH)、促卵泡激素(FSH)浓度;称双侧子宫湿质量,计算子宫系数。结果:旷场实验结果显示,更舒方高、低剂量组大鼠运动总路程长于模型组(P<0.01),雌激素组和更舒方中剂量组大鼠进入中央区次数增多(P<0.05),且雌激素组在中央区停留时间延长(P<0.01),更舒方低剂量组大鼠运动总路程长于坤泰组;高架十字迷宫实验结果显示,与对照组比较,模型组大鼠OE%低于对照组(P<0.05),雌激素组和更舒方高、中剂量组大鼠的OE%和OT%明显高于模型组(P<0.05),更舒方中剂量组大鼠OE%、OT%均高于坤泰组(P<0.01);更舒方高剂量组OT%高于坤泰组(P<0.01);明暗箱实验结果显示,模型组大鼠在明箱停留时间与对照组比较有减少的趋势,但差异无统计学意义(P>0.05),雌激素组和更舒方中剂量组大鼠在明箱停留时间明显长于模型组(P<0.05),舒更方低剂量组大鼠在明箱停留时间短于坤泰组(P<0.05)。血清激素水平及子宫系数结果显示,模型组大鼠血清FSH和LH含量明显高于对照组(P<0.05),子宫系数低于对照组(P<0.05);更舒方高、中剂量组大鼠血清E2含量高于模型组(P<0.05),FSH和LH含量低于模型组(P<0.05),子宫系数高于模型组(P<0.05),更舒方高、中、低剂量组大鼠血清E2均高于坤泰组,舒更方中剂量组大鼠子宫系数高于坤泰组。结论:更舒方可以有效调节卵巢去势围绝经期综合征大鼠的焦虑样行为,减缓体质量增长,更舒方中剂量组可以使血清中E2含量增加,降低FSH、LH含量,增加子宫系数,改善围绝经期综合征的症状。提示更舒方可以通过改善性激素水平调节围绝经期综合征的情绪症状,具有深度开发的前景。

Objective: To observe the effects of Gengshufang on behavioral characteristics, serum hormones and uterine coefficient of ovarian castration-perimenopausal syndrome model rats, and to explore the pharmacodynamic characteristics of Gengshufang against perimenopausal syndrome. Methods: The perimenopausal rats models were established by ovarian castration. A total of 48 rats successfully modeled were divided into model group, Kuntai group, 17-βestradiol + progesterone(estrogen group) and Gengshufang high, medium and low-dose groups according to their body weight according to the random division method. The sham-operation group was set as the control group. The estrogen group was administered by subcutaneous injection, and the other groups were administered by intragastric administration for 4 weeks. The open field experiment, elevated cross labyrinth experiment, and light and dark box experiments were performed within 24 hours after the last administration.Blood was taken from the abdominal aorta after peritoneal anesthesia with 10% chloral hydrate(30 mg/kg) and the uterus was removed. The serum estradiol(E2), luteinizing hormone(LH), and follicle stimulating hormone(FSH) were measured by ELISA. The wet mass of bilateral uterus was measured and the coefficient of uterus was calculated. Results: The results of open field experiments showed that the total exercise distance of rats in the Gengshufang high-dose and low-dose groups was longer than that in the model group(P<0.01). The number of rats entering the central area was increased in the estrogen group and the Gengshufang medium-dose group(P<0.05). In addition, the retention time of estrogen group in central area was prolonged(P<0.01). The total distance of exercise in the Gengshufang low-dose group was longer than that in the Kuntai group. The results of the elevated cross maze test showed that the OE% of the model group was lower than that of the control group(P<0.05), the OE% and OT% in the estrogen group, the Gengshufang high-dose and medium-dose group were significantly higher than those of the model group(P<0.05), the OE% and OT% of the Gengshufang mediumdose group were higher than those of Kuntai group(P<0.01), the OT% of the Gengshufang high-dose group was higher than that of Kuntai group(P<0.01). The results of the light and dark box experiment showed that the retention time in the light box of the model group was less than that in the control group, but the difference was not statistically significant(P>0.05). The time of rats in the estrogen group and the Gengshufang medium-dose group was significantly longer than that in the model group(P<0.05), and the time of rats in the Gengshufang low-dose group was shorter than that in the Kuntai group(P<0.05). The results of serum hormone levels and uterine coefficient showed that the levels of serum FSH and LH in the model group were significantly higher than those in the control group(P<0.05), and the uterine coefficient was lower than that in the control group(P<0.05). The content of serum E2 in the Gengshufang high, medium and low-dose group was higher than that in the model group(P<0.05), the levels of FSH and LH was lower than that in the model group(P<0.05), the uterine coefficient was higher than that in the model group(P<0.05). The serum E2 of rats in Gengshufang high,medium and low-dose groups was higher than that of Kuntai group, and the uterine coefficient of rats in Gengshufang medium-dose group was higher than that of Kuntai group. Conclusions: Gengshufang can effectively regulate the anxiety-like behavior of rats with ovarian castration and perimenopausal syndrome, and slow the growth of body mass. Gengshufang middle-dose group can increase the E2 content in the serum, reduce the FSH and LH content, increase the uterine coefficient, and improve the symptoms of perimenopausal syndrome. It suggested that Gengshufang can regulate the emotional symptoms of perimenopausal syndrome by improving the level of sex hormones, which has the prospect of further development.