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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(P<0.05)。停药60 d LH,FSH水平低于给药60 d,GnRH水平高于给药60 d(P<0.05)。给药30,60 d大鼠性周期紊乱率、动情间期天数高于正常组(P<0.05);给药60 d大鼠性周期紊乱率、动情间期天数高于给药30 d(P<0.05)。停药30 d性周期紊乱率高于正常组(P<0.05)。垂体指数:给药60 d高于正常组(P<0.05);停药30,60 d低于给药60 d(P<0.05)。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。
Objective: To observe the effect and its reversibility of total anthraquinone on the function and structure of hypothalamus and pituitary in female rats. Methods: Forty male Sprague-Dawley rats were randomly divided into normal group (n = 10), and the remaining 30 rats were given rhubarb total anthraquinone 73 mg · kg-1 for 60 days. Twenty-four hours after the last administration, one third of animals were sacrificed on the 30th and 60th days respectively. Serum levels of gonadotropin-releasing hormone (GnRH), luteinizing hormone (LH) and follicle stimulating hormone (FSH) were measured by enzyme-linked immunosorbent assay (ELISA) Hypothalamus and pituitary morphological changes were observed by staining. Results: The levels of FSH in the LH and FSH groups after administration for 60 d and 30 d after drug withdrawal were significantly higher than those in the normal control group (P <0.05). After 60 days of LH withdrawal, FSH levels were lower than 60 days after administration, and GnRH levels were higher than those of 60 days after drug administration (P <0.05). The rate of sexual cycle disorder and the number of days of estrus were significantly higher at 30 and 60 days after administration (P <0.05). The rate of sexual cycle disorder at 60 days after administration was higher than that at 30 days after administration <0.05). The discontinuation rate of 30-day cycle was higher than that of the normal group (P <0.05). Pituitary index: 60 d after administration was higher than that in the normal group (P <0.05); 30 and 60 d after drug withdrawal were lower than 60 d after drug administration (P <0.05). Histomorphological examination showed that hypothalamic neurons decreased with red neurons, ghost cells and chromatin margins at 60 d after dosing. Pituitary cells decreased, irregularly arranged, sinusoids dilated and eosinophils were adaptively proliferated. After 30 days of withdrawal, neurons in the hypothalamus increased, ghost cells and edges of the chromatin decreased, pituitary cells increased, sinusoids dilated and eosinophils decreased. 60 days after withdrawal, the pathological changes of hypothalamus and pituitary were further recovered. CONCLUSION: Total anthraquinone of Rhubarb after 60 days of gavage was toxic to sex hormones, sexual cycle and structure of hypothalamus and pituitary in female rats. However, this damage was reversible and recovered basically after 60 days’ withdrawal.