滋肾清热利湿化瘀方对多囊卵巢综合征小鼠C/EBPβ-STAT3信号通路的调节作用  

Regulation effect of Zishen Qingre Lishi Huayu Formula on C/EBPβ-STAT3 signaling pathway in polycystic ovary syndrome mice

作　　者：金晶 李欣 李佩双[2] 丁志玲 彭佳华[3] 梁瑞宁 JIN Jing;LI Xin;LI Peishuang;DING Zhiling;PENG Jiahua;LIANG Ruining(Graduate School of Jiangxi University of Chinese Medicine,Nanchang 330004,China;Affiliated Hospital of Jiangxi University of Chinese Medicine,Nanchang 333006,China;Institute of Obstetrics and Gynecology,Jiangxi University of Chinese Medicine,Nanchang 330006,China;The Second Affliated Hospital of Jiangxi University of CM,Nanchang 330012,China)

机构地区：[1]江西中医药大学研究生院,南昌330004 [2]江西中医药大学附属医院,南昌333006 [3]江西中医药大学中医妇产科学研究所,南昌333006 [4]江西中医药大学第二附属医院,南昌330012

出　　处：《中华中医药杂志》2023年第9期4365-4370,共6页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家自然科学基金项目(No.81560783,No.81860865,No.82060880);江西省中医妇产科疾病临床医学研究中心基金项目(No.20181BCG42003);江西中医药大学校级科技创新团队发展计划(No.CXTD22013);2022年大学生创新创业训练计划省级项目(No.S202210412070)。

摘　　要：目的:探讨滋肾清热利湿化瘀方(简称滋肾方)治疗多囊卵巢综合征(PCOS)可能机制。方法:将40只C57BL/6J小鼠随机分为4组:正常组、模型组、滋肾方组及枸橼酸氯米芬组,每组10只。除正常组外,其余各组来曲唑(LET)诱导PCOS模型,滋肾方组给予11.8 g·kg^(-1)·d^(-1)滋肾方,枸橼酸氯米芬组给予1 mg·kg^(-1)·d^(-1)枸橼酸氯米芬,正常组和模型组给予等体积0.9%氯化钠溶液,持续14 d。观察记录小鼠阴道动情周期及体质量;测量卵巢质量,计算卵巢质量指数;HE染色法进行卵巢组织病理学观察,并对黄体及囊性卵泡数量进行统计;ELISA法检测小鼠血清中促黄体生成素(LH)、卵泡刺激素(FSH)、睾酮(T)、白细胞介素(IL)-6、IL-10及肿瘤坏死因子-α(TNF-α)水平;Western Blot法检测转录因子CCAAT增强子结合蛋白β(C/EBPβ)、信号转导和转录活化因子3(STAT3)、磷酸化STAT3(p-STAT3)蛋白水平。结果:与模型组比较,经滋肾方干预后小鼠体质量增长率、卵巢质量、卵巢质量指数和囊性卵泡数量有不同程度下降(P<0.05,P<0.01),黄体数量显著升高(P<0.01);LH、LH/FSH、T、IL-6及TNF-α水平显著下降(P<0.01),FSH和IL-10水平显著上升(P<0.01);C/EBPβ蛋白表达量显著上调(P<0.01),p-STAT3/STAT3蛋白表达量显著下调(P<0.01)。结论:滋肾方能有效改善LET诱导的PCOS小鼠炎症损伤,可能是通过C/EBPβ-STAT3信号通路实现的。Objective:To investigate the possible mechanism of treating polycystic ovary syndrome(PCOS)with Zishen Qingre Lishi Huayu Formula.Methods:Forty C57BL/6J mice were randomly divided into 4 groups,namely normal group,model group,Zishen Qingre Lishi Huayu Formula(Zishen)group and Clomiphene citrate group,with 10 mice in each group.Except the normal group,the other groups were given Letrozole(LET)to induce PCOS model,the latter Zishen group was given 11.8 g·kg^(-1)·d^(-1)Zishen Qingre Lishi Huayu Formula,the clomiphene citrate group was given 1 mg·kg^(-1)·d^(-1)Clomiphene citrate,the normal group and model group were given equal volume 0.9%sodium chloride solution.It lasted for 14 days.Vaginal estrous cycle and body weight of mice were observed and recorded.Ovarian mass was measured and ovarian mass index was calculated.HE staining was used to observe the histopathology of the ovary,and the number of luteal corpus and cystic follicles were counted.Serum levels of luteinizing hormone(LH),follicle-stimulating hormone(FSH),testosterone(T),interleukin(IL)-6,IL-10 and tumor necrosis factor-α(TNF-α)were determined by ELISA.CCAAT enhancer binding proteinβ(C/EBPβ),signal transducer and activator of transcription 3(STAT3),phosphorylated STAT3(p-STAT3)protein levels were measured by Western Blot.Results:Compared with model group,the weight growth rate,ovarian mass,ovarian mass index and the number of cystic follicles of mice in the Zishen group were decreased to varying degrees(P<0.05,P<0.01),while the number of luteal body was significantly increased(P<0.01).The levels of LH,LH/FSH,T,IL-6,TNF-αin the Zishen group were significantly decreased(P<0.01),while the levels of FSH and IL-10 were significantly increased(P<0.01).The protein expression of C/EBPβin the Zishen group was up-regulated(P<0.01),and the protein expression of p-STAT3,STAT3 were down-regulated(P<0.01).Conclusion:Zishen Formula can effectively improve the inflammatory injury of letrozole-induced PCOS mice,which may be achieved through C/EBPβ-STAT3 signa

关 键 词：滋肾清热利湿化瘀方 多囊卵巢综合征 CCAAT增强子结合蛋白β 信号转导和转录活化因子3 机制 动物模型 炎症反应 性激素 

分 类 号：R285.5[医药卫生—中药学]