大黄总蒽醌对雌性大鼠下丘脑、垂体功能和结构的影响及可逆性

目的:观察大黄总蒽醌对雌性大鼠下丘脑和垂体功能及结构的影响及其可逆性。方法:SD雌性大鼠40只,随机取10只作为正常组,其余30只灌胃大黄总蒽醌73 mg·kg-1,连续60 d。于末次给药后24 h,停药30,60 d分别处死1/3动物。酶联免疫(ELISA)法检测大鼠血清促性腺激素释放激素(GnRH),黄体生成素(LH),卵泡刺激素(FSH)水平;记录性周期;取垂体称重,计算脏器指数;HE染色观察下丘脑、垂体形态学变化。结果:给药60 d和停药30 d LH,FSH水平高于正常组,GnRH水平低于正常组(P0.05)。停药60 d LH,FSH水平低于给药60 d,GnRH水平高于给药60 d(P0.05)。给药30,60 d大鼠性周期紊乱率、动情间期天数高于正常组(P0.05);给药60 d大鼠性周期紊乱率、动情间期天数高于给药30 d(P0.05)。停药30 d性周期紊乱率高于正常组(P0.05)。垂体指数:给药60 d高于正常组(P0.05);停药30,60 d低于给药60 d(P0.05)。组织形态学检测,给药60 d,下丘脑神经元减少,有红色神经元、鬼影细胞、染色质边集;垂体细胞减少,排列不规整,血窦扩张,嗜酸性细胞适应性增生。停药30 d,下丘脑神经元增加,鬼影细胞、染色质边极减少;垂体细胞增加,血窦扩张减轻,嗜酸性细胞增生减少。停药60 d,下丘脑和垂体的上述病理改变进一步恢复。结论:灌胃60 d大黄总蒽醌对雌性大鼠性激素水平、性周期和下丘脑、垂体组织结构均有毒性,但这种损害是可逆的,停药60 d基本恢复。

Effect of Rhubarb Total Anthraquinone on Function and Structure of Hypothalamus and Pituitary of Female Rats

Objective: To observe the effects of rhubarb total anthraquinone on function and structure of hypothalamus, pituitary and its reversibility in female rats. Method: Forty female SD rats were selected, in which 10 rats were randomly selected as normal control group, and the remaining 30 rats were administered orally with 73 mg·kg^-1 rhubarb total anthraquinone for 60 days. At 24 h, 30 d and 60 d after the last administration, 1/3 rats were put to death. ELISA was used to detect the gonadotropin-releasing hormone (GnRH), luteinizing hormone (LH) and follicle-stimulating (FSH) levels in serum. Their estrous cycle was recorded. The pituitary was collected and weighed to calculate the index of pituitary. The morphological changes in hypothalamus and pituitary were observed by HE staining. Result: The LH and FSH levels of the model group at 60 d after administration and 30 d after drug discontinuance were higher than that in the normal control group, and GnRH level was lower than that in normal control group (P<0.05). The LH and FSH level of the model group at 60 d after drug discontinuance were lower than that at 60 d after administration, GnRH level was higher than that at 60 d after administration (P<0.05). The rate of the estrous cycle disordered and the number of diestrus days of the model at 30 d and 60 d after administration were higher than that in normal control group (P<0.05). The rate of the estrous cycle disordered and the number of diestrus days of the model group at 60 d after administration were higher than that at 30 d after administration (P<0.05). The rate of disordered estrous cycle of the model group at 30 d after drug discontinuance was higher than that in normal control group (P<0.05). The indexes of pituitary of the model group at 60 d after administration was higher than normal control group (P<0.05); and that at 30 d and 60 d after drug discontinuance was lower than at 60 d after administration (P<0.05). Pathological examination showed that the hypothalamus neurons of the model group at 60 d after administration reduced, red neurons, ghost cells and chromatin side pole appeared; pituitary cells decreased and became irregular, blood sinus was expanded, adaptability of eosinophilic cell was proliferated. The hypothalamus neurons of the model group at 30 d after drug discontinuance increased, red neurons decreased, ghost cells and chromatin side pole reduced; pituitary cells increased, blood sinus expansion was reduced, adaptability of eosinophilic cell hyperplasia was reduced. Pathological changes of the hypothalamus and pituitary were further recovered in the model group at 60 d after drug discontinuance. Conclusion: Estrogen level, estrous cycle and structure of hypothalamus and pituitary in female rats were affected by 60 d oral administration with rhubarb total anthraquinone, which however is reversible at 60 d after drug discontinuance.