补天大造丸干预早期卵巢功能不全大鼠免疫功能的作用机制*

作者：杨永琴，申 剑，王帅哲，马睿玲，胡 杨，杨 燕

单位：甘肃中医药大学，甘肃 兰州 730000

引用：引用：杨永琴，申剑，王帅哲，马睿玲，胡杨，杨燕.补天大造丸干预早期卵巢功能不全大鼠免疫功能的作用机制[J].中医药导报,2025,31(6):49-54,66.

DOI：10.13862/j.cn43-1446/r.2025.06.009

PDF： 下载PDF

摘要：

目的：探究补天大造丸对早期卵巢功能不全大鼠免疫功能及细胞因子的影响。方法：60只大鼠随机取10只为空白对照组，其余50只大鼠均通过腹腔注射环磷酰胺（75 mg/kg）构建卵巢功能减退模型。将50只造模成功的大鼠随机分为模型对照组、阳性对照组、补天大造丸高剂量组、补天大造丸中剂量组、补天大造丸低剂量组，每组10只。补天大造丸高、中、低剂量组分别给予23.580、11.790、5.895 g/kg的补天大造丸灌胃，阳性对照组给予戊酸雌二醇片（补佳乐）灌胃，剂量为0.090 mg/（kg·d）。模型对照组与空白对照组则灌胃蒸馏水。所有灌胃操作均从造模当日开始，1次/d，连续28 d。模型对照组在造模后2周处死，其余各组在给药结束后，于动情间期处死。HE染色观察大鼠卵巢、子宫、组织变化，检测胸腺指数、脾脏指数、子宫指数及卵巢指数，血清性激素LH、FSH、E2、AMH及INH-B水平，血清炎症因子IL-2、IL-10及TGF-β水平。结果：相较于空白对照组，模型对照组大鼠卵巢组织存在显著萎缩现象，各级卵泡数量减少，卵泡结构遭到破坏，黄体不仅数量稀少而且发育状况不佳。与模型对照组比较，药物干预组呈现出明显的改善态势，窦卵泡、原始卵泡、初级卵泡、次级卵泡及成熟卵泡，卵细胞、卵丘、透明带、放射冠结构清晰可见，并且其卵泡外围环绕的颗粒细胞层数多于模型对照组，排列较为规则，黄体数量相比模型对照组更多，发育情况尚可。另外，与模型对照组比较，各给药组大鼠子宫内膜层出现明显增厚现象，腺腔增大，同时肌层也增厚，且排列紧密。与模型对照组比较，补天大造丸高、中、低剂量组大鼠胸腺指数、脾脏指数均下降（P＜0.01或P＜0.05）；与模型对照组比较，补天大造丸低、中、高剂量组子宫指数与卵巢指数均升高（P＜0.01或P＜0.05）。与模型对照组比较，补天大造丸高、中剂量组大鼠血清中LH、FSH水平下降（P＜0.01），补天大造丸低剂量组大鼠血清中LH下降（P＜0.05），FSH水平无明显变化（P＞0.05）；与模型对照组比较，补天大造丸高、中剂量组大鼠血清中E2、AMH、INH-B水平上升（P＜0.01），补天大造丸低剂量组E2、AMH水平上升（P＜0.05），INH-B水平无明显变化（P＞0.05）；与模型对照组比较，阳性对照组与补天大造丸高、中、低剂量组大鼠血清IL-2、TGF-β水平下降（P＜0.01或P＜0.05），IL-10表达上升（P＜0.01或P＜0.05）。结论：补天大造丸可调节免疫性早发性卵巢功能不全小鼠的血清生殖激素与细胞因子水平，减轻卵巢炎症反应，有效调控免疫紊乱状态，显著提升卵巢储备能力，发挥保护作用，从而为卵巢构建起一道防护屏障。

关键词：早发性卵巢功能不全；补天大造丸；TGF-β；IL-2；IL-10；大鼠

Abstract：

Objective: To explore the effects of Butian Dazao pill on the immune function and cytokines in rats with premature ovarian insufficiency. Methods: A total of 10 rats were randomly selected as blank group from 60 rats. Except for the blank group, the remaining rats were given a single intraperitoneal injection of cyclophosphamide at a dose of 75 mg/kg to construct a model of ovarian hypofunction. After the successful replication of the model, 50 successfully modeled rats were randomly divided into model control group, positive control group, high dose group of Butian Dazao pill (high dose group), medium dose group of Butian Dazao pill (medium dose group), and low dose group of Butian Dazao pill (low dose group), with 10 rats in each group. The high, medium and low dose groups were given Butian Dazao pill at doses of 23.580, 11.790, and 5.895 g/kg respectively. The positive control group was given Progynova at a dose of 0.090 mg/（kg·d） for intragastric administration. The model control group and the blank group were given distilled water for intragastric administration. The intragastric administration was started on the day of model construction, once a day for 28 consecutive days. The rats in the model control group were executed during the diestrus stage 2 weeks after model construction, and the rats in the other groups were executed during the diestrus stage after the end of drug administration. The changes in the ovaries, uteri, and tissues were observed by HE staining. The thymus index, spleen index, uterine index, and ovarian index were detected. The expression levels of serum LH, FSH, E2, AMH, INH-B, IL-2, IL-10 and TGF-β were measured. Results: HE staining showed that, compared with the blank group, the ovarian tissues of the rats in the model control group were significantly atrophied under naked-eye observation, and that the number of follicles at all levels was reduced. The follicular structure was damaged in model group, and the corpora lutea were few and poorly developed. Compared with the model control group, the drug intervention groups showed improvements. Sinus follicles, primordial follicles, primary follicles, secondary follicles, and mature follicles could be seen in positive control group, high dose group, medium dose group , and low dose group. The structures of oocytes, cumulus oophorus, zona pellucida, and corona radiata could be seen. The positive control group, high dose group, medium dose group, and low dose group showed more layers of granulosa cells surrounding the follicles than model control group, and they were arranged regularly. The positive control group, high dose group, medium dose group, and low dose group showed more corpora lutea than model control group, and their development was acceptable. Compared with the model control group, the endometrial layer was significantly thickened in positive control group, high dose group, medium dose group, and low dose group showed more. The glandular cavity was enlarged, and the muscular layer was thickened and arranged densely in positive control group, high dose group, medium dose group, and low dose group showed more. Compared with the model control group, the thymus index and spleen index decreased in high, medium and low dose group (P<0.05 or P<0.01). Compared with the model control group, the uterine index and ovarian index increased in high, medium and low dose groups (P<0.01 or P<0.05). Compared with the model control group, the levels of LH and FSH in the serum decreased in high and medium dose group (P<0.01). The level of LH in the serum decreased in low dose group (P<0.05), while the level of FSH showed no significant change in low dose group (P>0.05). Compared with the model control group, the levels of E2, AMH, and INH-B in the serum increased in the high and medium dose groups (P<0.01). The levels of E2 and AMH in the serum increased in low dose group (P<0.05), while the level of INH-B showed no significant change in low dose group (P>0.05). Compared with the model control group, the level of serum IL-2 and TGF-β decreased in Progynova group, high dose group, medium dose group and low dose group (P<0.01 or P<0.05), while the expression of IL-10 increased in Progynova group, high dose group and medium dose group (P<0.01 or P<0.05). Conclusion: Butian Dazao pill can improve the levels of serum reproductive hormones and cytokines in mice with immune premature ovarian insufficiency, reduce the ovarian inflammatory reaction, regulate the immune disorder, improve the ovarian reserve capacity, and play a protective role in the ovaries.

Key words：premature ovarian insufficiency; Butian Dazao pill; TGF-β, IL-2; IL-10; rat

发布时间：2026-01-03

点击量：56