摘要
目的基于“阴平阳秘”理论研究昼夜节律紊乱对多囊卵巢综合征(PCOS)模型大鼠性激素及卵巢形态的影响及作用机制。方法SD大鼠采用脱氢表雄酮(DHEA)注射法构建PCOS模型,观察大鼠一般情况,造模第12天开始阴道涂片观察动情周期,造模结束后,ELISA检测血清促黄体生成素(LH)、卵泡刺激素(FSH)、雌二醇(E2)、总睾酮(T)水平。成功制备PCOS模型大鼠30只,随机分为PCOS组(正常光照),PCOS+PL组(长光照),PCOS+CL组(持续光照),各10只;同时设置10只大鼠为对照组(正常光照)。光照处理结束后,所有大鼠均断颈取血并收集卵巢组织,检测各组大鼠卵巢相对质量,同时采用HE染色观察卵巢组织形态并进行有腔卵泡和囊状卵泡计数。透射电镜观察卵巢组织超微结构变化。蛋白质印迹法检测骨形态发生蛋白(BMP)、Smad4、Smad1/5/9蛋白表达水平的变化。结果PCOS组大鼠表现无规则动情周期,表明PCOS大鼠模型制备成功。与PCOS组相比,PCOS+PL组和PCOS+CL组大鼠体重、卵巢系数降低,卵巢组织形态加重且有腔卵泡和囊状卵泡数量增加,血清中LH、E2和T激素水平显著增加,而FSH激素水平显著降低,BMP6、Smad4、Smad1/5/9蛋白表达下调,光照时间越长PCOS的症状越严重。结论昼夜节律紊乱会加重PCOS模型大鼠性激素水平异常、卵巢囊性改变,可通过下调BMP/Smad信号通路进而加速PCOS的发展。
Objective Based on the“Balance Between Yin and Yang”theory,this study investigated the effects and mechanisms of circadian rhythm disruption on hormone levels and ovarian morphology in a rat model of Polycystic Ovary Syndrome(PCOS).Methods SD rats were used to establish a polycystic ovary syndrome(PCOS)model through the injection of dehydroepiandrosterone(DHEA).The general condition and body weight of the rats were observed,and vaginal smears were taken from day 12 of modeling to observe the estrous cycle.After modeling,ELISA was performed to measure serum levels of luteinizing hormone(LH),follicle-stimulating hormone(FSH),estradiol(E2),and total testosterone(T).A total of 30 PCOS model rats were successfully prepared and randomly divided into three groups:PCOS model group,PCOS+prolonged light exposure group,and PCOS+continuous light exposure group,with ten rats in each group.Additionally,a control group of ten rats with normal sleep schedules were also set.After light treatment,blood samples were collected by decapitation for analysis,and ovarian tissues were collected to measure relative ovarian mass.HE staining was used to observe the morphology of ovarian tissue and the number of antral follicles and cystic follicles.Transmission electron microscopy was used to observe ultrastructural changes in ovarian tissue.Western blotting detected changes in bone morphogenetic protein(BMP),Smad4,Smad1/5/9 protein expression levels.Results The PCOS model in rats exhibited irregular estrous cycles,indicating successful preparation of the PCOS rat model.Compared to the PCOS group,the rats in the PCOS+PL group and PCOS+cCL group showed reduced body weight and ovarian coefficient,aggravated ovarian tissue morphology with increased numbers of antral follicles and cystic follicles,significantly increased levels of LH,E2,and T hormones in serum.In contrast,FSH hormone level was significantly decreased.Additionally,protein expression of BMP6,Smad4,and Smad1/5/9 was downregulated.The longer the light exposure,the more severe of PCOS symptoms.Conclusion Disruption of circadian rhythm exacerbates abnormal hormone levels and ovarian cystic changes in PCOS model rats,accelerating the occurrence and development of PCOS by downregulating the BMP/Smad signaling pathway.
作者
陈艳
王帅
宗惠
李小叶
韩竹林
尚文霞
张丁艳
CHEN Yan;WANG Shuai;ZONG Hui;LI Xiaoye;HAN Zhulin;SHANG Wenxia;ZHANG Dingyan(Shanxi University of Chinese Medicine Affiliated Hospital,Shanxi Province,Taiyuan 030024 China)
出处
《中国生育健康杂志》
2026年第1期29-35,共7页
Chinese Journal of Reproductive Health
基金
山西省中医药管理局项目(2023ZYYB2012)
山西中医药大学附属医院青年基金培育项目(QN202203)
马堃“岐黄学者”工作室。