鳖甲煎丸对子宫肌瘤模型大鼠血清激素水平及子宫组织病理改变的影响

Effects of Biejiajianwan on serum hormone level and the pathologic change of uterus in rats' uterine myoma

目的研究鳖甲煎丸的抗子宫肌瘤作用。方法选用雌性SD大鼠,随机分为正常对照组,去势对照组,雌孕激素负荷模型组,米非司酮阳性对照组（2.25 mg/kg）,鳖甲煎丸高、中和低三个剂量（3.0,1.5,0.75 g/kg）组。除正常对照组外其余6组均行双侧卵巢切除术。除正常对照组及去势对照组外,各组均采用雌激素孕激素联合法造成雌性大鼠子宫肌瘤模型,于注射雌激素10周后,经口灌胃给予鳖甲煎丸和阳性对照药米非司酮,为期2个月。给药期末通过子宫的大体观、脏器系数、血清雌孕激素水平测定结果,以及子宫雌孕激素受体免疫组化检测、HE染色和Masson染色结果,评价鳖甲煎丸对抗试验性子宫肌瘤的作用。结果 1鳖甲煎丸连续经口给药2个月,大鼠血清雌孕激素水平虽无显著变化,但子宫在雌激素孕激素作用下的过度增生得到轻度抑制;2 HE染色及Masson染色结果显示,与雌孕激素负荷模型组比较,鳖甲煎丸组子宫内膜和肌层增厚明显减轻,子宫纤维化组织的含量明显减少（P〈0.05）;3雌孕激素受体的免疫组化染色结果显示,模型动物子宫在长期大量雌激素和孕激素的作用下,子宫内膜和肌层的雌孕激素受体均明显增多。鳖甲煎丸组子宫雌激素受体无显著变化,但与模型组比较,鳖甲煎丸3.0及1.5 g/kg剂量组的子宫孕激素受体数量明显减少（P〈0.01或0.05）。结论鳖甲煎丸对雌激素孕激素负荷大鼠的子宫肌瘤具有一定治疗作用,其有效剂量为1.5~3.0 g/kg。

Objective To observe the effects of Biejiajianwan on serum sex hormone level and the pathologic change of uterus in rats with hysteromyoma. Methods The female SD rats were divided randomly into the control group, the ovariectomized group, the model group（rats ovariectomized and loaded by Estradiol and Progesterone）, the mifepristone group（2.25 mg/kg）,the Biejiajianwan low, moderate and high dose groups（3.0, 1.5, 0.75 g/kg）. Except the control group, the rats were ovariectomized or/and injected with estradiol and progesterone to establish uterine leiomyoma-like hyperplasia model.For 10 weeks after the first estradiol injection, the rats were treated with Beijiajianwan（3.0, 1.5, 0.75, 0.375 g/kg） and mifeoristone（2.25 mg/kg） per oral for 8 weeks. At the end of experimental course, the uterus weights and the body weights were recorded,and the levels of serum sex hormone were detected by Elisa. The morphological features and the thickness of the uterine smooth muscle were observed by means of Masson staining, HE staining and immunohistochemical method. Results 1Beijiajianwan had no obvious effects on uterus weight index and the levels of serum sex hormone（progesterone, estradiol）. 2 Compared with the model group, histopathological assessment showed that 3.0, 1.5, 0.75 g/kg Beijiajianwan could decrease the thickness of the uterine smooth muscle, improve smooth muscle fibre hypertrophy（P〈0.05, model group） with the stain of HE and Masson. 3 Immunohistochemical analysis showed that although Beijiajianwan has no effects on the estrogen receptor expression in myometrial and endometrium of uterus compared with model group（P〉0.05）, Beijiajianwan（3.0, 1.5g/kg） could down-regulate progesterone receptor expression significantly in both myometrial and endometrium of uterus（P〈0.05, P〈0.01, model group）.Conclusion Beijiajianwan could minished the degree of myometrium incrassation and pathomorphological changes of uterus of rats loaded by estradiol and progesterone, the effective dosage of Beijiajianwan was 1.5~3.0 g/kg in rat.