加味半夏泻心汤对多囊卵巢综合征合并胰岛素抵抗模型大鼠肠道菌群及炎症因子的影响  

Effect of Jiawei Banxia Xiexin Decoction(加味半夏泻心汤)on Gut Microbiota and Inflammatory Factors in Polycystic Ovarian Syndrome with Insulin Resistance Model Rats

作　　者：赵红玉 陈如枫 郑冬雪 贾凡 刘津源 刘咏梅[1] 阚杰[1] 赵林华[1] 刘新敏[1] ZHAO Hongyu;CHEN Rufeng;ZHENG Dongxue;JIA Fan;LIU Jinyuan;LIU Yongmei;KAN Jie;ZHAO linhua;LIU Xinmin(Guang'anmen Hospital,China Academy of Chinese Medical Sciences,Beijing,100053;Beijing University of Chinese Medicine)

机构地区：[1]中国中医科学院广安门医院,北京市100053 [2]北京中医药大学

出　　处：《中医杂志》2022年第21期2072-2080,共9页Journal of Traditional Chinese Medicine

基　　金：国家自然科学基金(81674011)。

摘　　要：目的 探讨加味半夏泻心汤治疗多囊卵巢综合征(PCOS)合并胰岛素抵抗(IR)的可能作用机制。方法 78只SD大鼠随机分为空白组15只和造模组63只。造模组大鼠使用来曲唑联合高脂饮食构建PCOS-IR大鼠模型。将造模成功的60只大鼠随机分为模型组、二甲双胍组和加半高、中、低剂量组,每组12只。二甲双胍组给予盐酸二甲双胍0.1575 g/(kg·d),加半高、中、低剂量组分别给予加味半夏泻心汤26.46、13.23、6.615 g/(kg·d),模型组、空白组给予2 ml生理盐水,各组均灌胃2周后检测大鼠体质量、血糖(Glu)及血清空腹胰岛素(FINS),计算稳态模型胰岛素抵抗指数(HOMA-IR);测量卵巢重量,计算卵巢脏器系数,HE染色法观察大鼠卵巢的病理学改变;ELISA法检测血清雌二醇(E2)、睾酮(T)、黄体生成素(LH)、卵泡刺激素(FSH)、FINS、脂多糖(LPS)、肿瘤坏死因子α (TNF-α)、白细胞介素6 (IL-6)水平,并计算LH/FSH值;采用16S rRNA技术检测大鼠粪便的肠道菌群的Alpha、Beta多样性及物种组成差异。结果与空白组相比,模型组大鼠体质量升高、卵巢脏器系数降低,血清T、FSH、LH、LH/FSH、Glu、HOMA-IR及LPS均升高(P<0.05),病理结果显示卵巢较多囊状扩张卵泡,颗粒细胞减少,未见黄体,肠道菌群chao指数、ace指数、shannon指数有升高趋势,但差异均无统计学意义(P>0.05),疣微菌门、阿克曼菌属及异杆菌属丰度下降(P<0.05)。与模型组相比,各给药组大鼠体质量下降、卵巢脏器系数升高,chao、ace指数均下降(P<0.05),各给药组颗粒细胞及黄体数目增多,且加半高剂量组可见到成熟卵泡;二甲双胍组T水平、shannon指数、拟杆菌门、放线菌门、未命名的鼠尾草科、葡萄球菌属下降,E_(2)及LPS水平升高(P<0.05);加半高剂量组HOMA-IR、LPS、TNF-α水平、shannon指数下降,变形菌门升高(P<0.05);加半中、低剂量组E、T、FSH、LH水平升高,LH/FSH水平、狭义梭菌属、葡萄球�ObjectiveTo explore the possible mechanism of Jiawei Banxia Xiexin Decoction(加味半夏泻心汤,JBXD)in treatment of polycystic ovary syndrome with insulin resistance(PCOS-IR).MethodsA total of 78 SD rats were randomly divided into control group(n=15)and modeling group(n=63).PCOS-IR model was established using letrozole combined with high fat diet.Sixty successful modeling rats were randomly divided into a model group,metformin group,high-,medium-,and low-dose JBXD group,with 12 rats in each group.Corresponding administra-tions were given to each group by gavage for 2 weeks,including 0.1575 g/(kg·d)of metformin hydrochloride for met-formin group,26.46,13.23,and 6.615 g/(kg·d)JBXD for high-,medium-,and low-dose JBXD group,and 2 ml of normal saline for model group and control group.The body weight,blood glucose(Glu)and serum fasting insulin(FINS)were tested,and homeostasis model assessment of insulin resistance(HOMA-IR)was calculated.The ovary was weighted,and organ coefficient was calculated.The pathological changes of ovary were observed through HE staining.Serum estradiol(E2),testosterone(T),luteinizing hormone(LH),follicle-stimulating hormone(FSH),li-popolysaccharide(LPS),tumor necrosis factorα(TNF-α),and interleukin 6(IL-6)were determined by ELISA,and LH/FSH ratio was calculated.The Alpha and Beta diversity and species composition differences of gut microbiota in rat feces were detected by 16S rRNA technology.ResultsCompared to those in the control group,the weight of rats in the model group increased,with decreased ovarian organ coefficient and increased serum T,FSH,LH,LH/FSH,Glu,HOMA-IR and LPS(P<0.05).The ovaries of rats in the model group had more cystic dilated follicles,decreased number of granulosa cells and no corpus luteum.In the model group,chao index,ace index and shannon index increased,but the difference was not statistically significant(P>0.05).In the model group,the abundance of Verrucomicrobia,Akkermansia and Allobaculum decreased(P<0.05).Compared to those in the model group,the weight o

关 键 词：多囊卵巢综合征 胰岛素抵抗 肠道菌群 炎症因子 性激素 加味半夏泻心汤 

分 类 号：R285.5[医药卫生—中药学]