寿胎丸加味方对多囊卵巢综合征高雄激素-胰岛素抵抗流产模型大鼠炎症反应和子宫内膜容受性相关因子表达的影响  

Effect of Modified Shoutai Pill(寿胎丸加味方)on Inflammatory Reaction and Expression of Endometrial Receptivity-Related Factors in A Rat Model of Polycystic Ovary Syndrome and Miscarriage with High Testosterone-Insulin Resistance

作　　者：郭婷婷 蒋蒙 杨怀影 吉翔 张跃辉 GUO Tingting;JIANG Meng;YANG Huaiying;JI Xiang;ZHANG Yuehui(Heilongjiang University of Chinese Medicine,Harbin,150040;First Affiliated Hospital,Heilongjiang University of Chinese Medicine,Harbin,150040)

机构地区：[1]黑龙江中医药大学,黑龙江省哈尔滨市150040 [2]黑龙江中医药大学附属第一医院

出　　处：《中医杂志》2025年第3期275-282,共8页Journal of Traditional Chinese Medicine

基　　金：国家自然科学基金(82074259,82374286);黑龙江省青年岐黄学者培养项目(黑中医药教函[2023]36号);黑龙江中医药大学“优秀青年学术带头人”科研项目。

摘　　要：目的从炎症反应和子宫内膜容受性探讨寿胎丸加味方治疗多囊卵巢综合征高雄激素-胰岛素抵抗流产的可能作用机制。方法将动情周期规律且处于动情前期的SPF级雌性SD大鼠30只与SPF级雄性SD大鼠15只,于每日18:00按2∶1比例合笼,次日8:00雌鼠阴道涂片镜下观察到大量精子且见阴道栓视为妊娠第0.5天,共获得30只孕鼠。在妊娠第0.5天将孕鼠随机分为正常组、模型组、寿胎丸加味方组,每组10只。自妊娠第0.5天至第13.5天,寿胎丸加味方组予寿胎丸加味方药液26.6 g/(kg·d)灌胃,每天2次,连续14天;正常组和模型组同时予生理盐水4 ml/只灌胃。除正常组外,其余两组孕鼠自妊娠第7.5天至第13.5天联合应用双氢睾酮(DHT)和胰岛素(INS)腹腔注射连续7天,建立多囊卵巢综合征高雄激素-胰岛素抵抗流产大鼠模型。妊娠第13.5天对孕鼠进行口服葡萄糖耐量试验(OGTT),检测0、30、60、90、120 min时血糖水平;妊娠第14.5天取材,ELISA法检测孕鼠血清中孕酮(P4)、雌二醇(E2)、空腹胰岛素(FINS)、白细胞介素6(IL-6)、肿瘤坏死因子α(TNF-α)水平,并计算胰岛素抵抗指数(HOMA-IR);观察孕鼠胚胎着床情况,计算流产率、平均活胎数;HE染色观察子宫组织病理形态;qRT-PCR法检测孕鼠子宫组织中Il-6、Tnf-α、白血病抑制因子(Lif)、同源框基因10(Hoxa10)、催乳素家族8亚家族a成员2(Prl8a2)、胰岛素样生长因子结合蛋白1(Igfbp1)mRNA表达。结果与正常组比较,模型组孕鼠在0、30、60、90、120 min时血糖均升高,流产率及HOMA-IR升高,平均活胎数减少,血清中P4、E2水平降低,IL-6、TNF-α、FINS水平升高,子宫组织中Il-6、Tnf-αmRNA表达升高,Lif、Hoxa10、Prl8a2 mRNA表达降低(P<0.05或P<0.01);子宫颜色暗红,可见宫腔内有多处明显瘀血,胚胎数量减少且发育不良,胎盘出血坏死增多,吸收胚胎和血胚较多;病理形态示子宫蜕膜层存在血栓,蜕膜细胞形态不清晰,Objective To explore the possible mechanisms of Modified Shoutai Pill(寿胎丸加味方,MSP)in treating polycystic ovary syndrome(PCOS)with hyperandrogenism,insulin resistance,and miscarriage,focusing on inflammatory response and endometrial receptivity.Methods Thirty female SPF-grade SD rats with regular estrous cycles and in proestrus,and 15 male SPF-grade SD rats were housed together in a 2∶1 ratio at 18:00.At 8:00 next morning,rats showing abundant sperm and vaginal plugs were considered pregnant on the day 0.5.The 30 pregnant rats were randomly divided into three groups,normal group,model group,and MSP group,with 10 rats in each group.From day 0.5 to day 13.5 of pregnancy,the MSP group was given 26.6 g/(kg·d)of the MSP via gavage twice a day for 14 consecutive days.The normal group and the model group received 4 ml of normal saline daily.From day 7.5 to day 13.5 of pregnancy,the rats in the model group and MSP group were intraperitoneally injected with dihydrotestosterone(DHT)and insulin(INS)for 7 consecutive days to establish a PCOS model with hyperandrogenism,insulin resistance,and miscarriage.On day 13.5 of pregnancy,an oral glucose tolerance test(OGTT)was performed to measure blood glucose levels at 0,30,60,90,and 120 minutes.On day 14.5,serum level of progesterone(P4),estradiol(E2),fasting insulin(FINS),interleukin-6(IL-6),and tumor necrosis factor-alpha(TNF-α)were measured by ELISA.The insulin resistance index(HOMA-IR)was calculated.Embryo implantation,miscarriage rate,and average number of live fetuses were observed.Uterine tissue pathology was examined by HE staining,and mRNA expression of Il-6,Tnf-α,leukemia inhibitory factor(Lif),homeobox gene 10(Hoxa10),prolactin family 8 subfamily A member 2(Prl8a2),and insulin-like growth factor-binding protein 1(Igfbp1)in the uterine tissue was detected by qRT-PCR.Results Compared with the normal group,the model group had significantly higher blood glucose level at 0,30,60,90,and 120 minutes,increased miscarriage rate,elevated HOMA-IR,decreased average nu

关 键 词：多囊卵巢综合征 高雄激素血症 胰岛素抵抗 流产 寿胎丸 炎症因子 子宫内膜容受性 

分 类 号：R285.5[医药卫生—中药学]