促排合剂对肾阳虚排卵障碍模型大鼠生殖调控机制研究

目的] 探讨促排合剂对肾阳虚排卵障碍模型大鼠生殖内分泌功能影响的作用机制。方法] 本实验以60只雌性SD健康大鼠为研究对象，选择目前应用最多的肌注氢化可的松的方法来制备肾阳虚排卵障碍大鼠模型，模型制备成功后，按照随机数字表法随机分为6组，每组10只，分别建立空白对照组、模型对照组、氯米芬阳性组、促排合剂低、中（正常）、高剂量组。空白对照组每日灌服生理盐水1 mg/100 g，促排合剂组按等效剂量0.5、1、2倍作为低、中、高剂量组给药剂量标准给药15 d，氯米芬阳性组大鼠剂量为4.5 mg/kg，模拟人的月经周期，在15 d的治疗期（3个性周期），每个性周期的前2 d给药，后3 d停药。各组干预15 d后，动情期处死大鼠。处死前观察并记录大鼠动情周期变化，测定不同组大鼠体质量及脏器质量系数，检测下丘脑-垂体-卵巢轴（HPO轴）、下丘脑-垂体-肾上腺轴（HPA轴）相关激素和氧化应激反应相关因子水平变化。结果] 氯米芬阳性组、促排合剂低、中、高剂量组大鼠体质量均显著高于模型对照组水平（P<0.05）；氯米芬阳性组、促排合剂低、中、高剂量组大鼠各脏器质量系数均显著高于模型对照组水平（P<0.05）；氯米芬阳性组、促排合剂低、中、高剂量组大鼠血清孕酮（P）、促性腺激素释放激素（GnRH）、卵泡刺激素（FSH）、黄体生成素（LH）和血清雌二醇（E2）含量水平均显著低于空白对照组水平，而均显著高于模型对照组水平（P<0.05）；氯米芬阳性组、促排合剂低、中、高剂量组大鼠血清肾上腺皮质激素（ACTH）和皮质醇（COR）含量水平均显著低于空白对照组水平，然而均显著高于模型对照组水平（P<0.05）；氯米芬阳性组、促排合剂低、中、高剂量组大鼠血清总超氧化物歧化酶（T-SOD）和过氧化氢酶（CAT）含量水平均显著低于空白对照组水平，丙二醛（MDA）含量水平显著高于空白对照组水平，然而T-SOD和CAT含量水平均显著高于模型对照组水平，且MDA含量水平显著高于模型对照组水平（P<0.05）。结论] 促排合剂可通过改善下丘脑-垂体-靶腺轴调节功能和缓解氧化应激反应的相关机制，促进肾阳虚大鼠生殖功能的改善和生殖器官的发育，为该制剂的临床推广提供了一定的药理学依据。

Study on reproductive regulation mechanism of Cupai Heji on ovulation disorder model rats with kidney yang deficiency

Objective] To explore the mechanism of the effect of Cupai Heji on reproductive endocrine function of ovulation disorder model rats with kidney yang deficiency.Methods] The 60 healthy female SD rats were randomly divided into 6 groups according to the random number table method,with 10 rats in each group. Blank control group,model control group,clomiphene positive group,low dose,medium dose,and high dose groups of Cupai Heji were established respectively. Before death,the changes of estrous cycle of rats were observed and recorded,body weight and organ weight coefficient of rats in different groups were measured,and levels of hormones and factors related to oxidative stress response of hypothalamic pituitary ovarian axis (HPO axis) and hypothalamic pituitary adrenal axis (HPA axis) were detected.Results] The body weight of rats in clomiphene positive group,low dose group,medium dose group and high dose group were significantly higher than those in model control group (P<0.05). The weight coefficients of various organs in clomiphene positive group,low,medium and high dose groups were significantly higher than those in model control group (P<0.05). The levels of serum P,GnRH,FSH,LH and E2 in clomiphene positive group,low,medium and high dose groups were significantly lower than those in blank control group,but significantly higher than those in model control group (P<0.05). The levels of serum ACTH and COR in clomiphene positive group,low,medium,and high dose groups were significantly lower than those in blank control group,but significantly higher than those in model control group (P<0.05). The levels of serum T-SOD and CAT in clomiphene positive group,low,medium and high dose groups were significantly lower than those in blank control group,and the levels of mad were significantly higher than those in blank control group. However,the levels of T-SOD and CAT were significantly higher than those in model control group,and the levels of mad were significantly higher than those in model control group (P<0.05).Conclusion] Cupai Heji can promote the improvement of reproductive function and the development of reproductive organs in rats with kidney yang deficiency by improving the regulatory function of hypothalamus pituitary target gland axis and alleviating oxidative stress,which provides some pharmacological basis for the clinical promotion of Cupai Heji.