A preliminary study on the effects of Xiang shao granules on reproductive endocrinology in drugged ovariectomised rats
Authors: Tang Huimin , Jia Qiucheng , Chen Wanying , Wu Yihan , Wei Weiwei , Zheng Hong , Chen Jiming 
Published: March 2024

Objective: To establish a rat model of pharmacological ovariectomy by GnRH-a injection, and to preliminarily investigate the reproductive endocrine effects of Xiangshao granules on pharmacological ovariectomised rats.
Methods: A rat model of pharmacological ovariectomy was established by injecting female rats with GnRH-a. The rats were randomly divided into four groups: GnRH-a injected saline group (GnRH-a + NS); GnRH-a injected oestradiol group (GnRH-a + E2); GnRH-a injected Xiang shao granule group (GnRH-a + Xiang shao), and the control group of saline injected rats (NS + NS). according to the observation of the vaginal smear of the rats to determine the success of the modelling, after the success of the modelling of the corresponding drug gavage intervention for 28 days, every other day to weigh the body weight of the rats and measure the anal temperature, according to the changes in body weight of the rats to adjust the amount of drug intervention. Plasma sex hormone levels (E2, FSH, LH), uterine weight, uterine index and endometrial histomorphological changes, and ovarian weight, ovarian index and ovarian histomorphological changes were measured in each group after gavage.
Results: (1) Vaginal cell smears of rats in the control group (NS+NS) showed changes in the estrous cycle, whereas vaginal cell smears of rats in the GnRH-a+NS, GnRH-a+E2, and GnRH-a+Xiang shao groups showed no changes in the estrous cycle; (2) The body mass gain of rats in the GnRH-a+NS, GnRH-a+E2, and GnRH-a+Xiang shao groups was significantly higher than that of the NS+NS group, whereas intervention with estradiol (E2) and peony granules significantly slowed down the GnRH-a induced body mass gain. NS group, while the intervention of estradiol (E2) and Xiang shao granules could significantly delay the trend of GnRH-a-induced body mass gain in rats; (3) The anal temperature of rats after GnRH-a injection showed an overall increasing trend, and compared with GnRH-a+NS, the body temperature of rats in GnRH-a+E2 and GnRH-a+Xiang shao groups showed a gradual decreasing trend, and the decreasing of the temperature in Xiang shao granules compared with that of rats in E2 group was (4) Plasma sex hormone levels (E2, FSH, LH) were significantly lower in the GnRH-a+NS, GnRH-a+E2, and GnRH-a+Xiang shao groups than in the NS+NS group (P<0.001), and the levels of E2 in the GnRH-a+E2 and GnRH-a+Xiang shao groups were significantly higher than those in the GnRH-a+NS group (P<0.001, P<0.05), and the levels of E2 in the GnRH-a+NS group were significantly lower than those in the GnRH-a+Xiang shao group (P<0.001, P<0.05). 0.05), and the E2 level in GnRH-a+E2 group was higher than that in GnRH-a+Xiangshao Granules group (P<0.05); the FSH level in GnRH-a+E2 group was significantly lower than that in GnRH-a+ Xiangshao granules group (P<0.05), and there was a slight downward trend in the FSH level of GnRH-a+E2 group compared to that of GnRH-a+NS, but the difference was not statistically significant (P> 0.05); LH levels in the GnRH-a+E2 group were significantly lower than those in the GnRH-a+NS and GnRH-a+Xiang shao groups (P<0.001, P=0.001), whereas there was no significant difference in the LH and FSH levels between the two groups, GnRH-a+NS and GnRH-a+ Xiang shao groups (P>0.05); (5) compared with the NS+NS group, GnRH-a injected rats in each model, uterine weight and uterine index, ovarian weight and ovarian index were significantly decreased (P<0.001); comparing between the groups, the uterine weight and uterine index, ovarian weight and ovarian index of GnRH-a+ E2 and GnRH-a+Xiang shao groups were significantly higher than those of GnRH-a+NS group (P<0.001, P<0.05); uterine weight and uterine index, ovarian weight and ovarian index of GnRH-a+E2 group were significantly higher than those of GnRH-a+NS group (P<0.001, P<0.05); and uterine weight and uterine index, ovarian weight and ovarian index were elevated compared with the GnRH-a+Xiang shao group (P<0.05); (6) compared with the NS+NS group, the number of primordial follicles was significantly higher and the number of growing follicles and mature follicles was significantly lower in the GnRH-a+NS, GnRH-a+E2 and GnRH-a+Xiang shao groups; (7) the number of rats' uterine wall was significantly higher and the number of rats' uterine wall was significantly lower in the NS+NS group than in the GnRH-a NS+NS group and GnRH-a group, the uterine wall of rats in each group was significantly thinner, the endothelial layer was atrophied, the thickness of the uterine wall increased in the GnRH-a+E2 and GnRH-a+Xiang shao groups, and the number of vaginal folds and blood vessels also increased. Among them, the improvement of uterus and vagina was more obvious in GnRH-a+E2 than in GnRH-a+NS and GnRH-a+Xiangshao groups.
Conclusion: GnRH-a injection could reduce the levels of sex hormones E2, FSH and LH in rats, causing perimenopausal symptoms such as hot flashes, while E2 and Xiang shao granules significantly improved such symptoms, and Xiang shao granules had a slight oestrogenic effect, but to a lesser extent than E2.