健脾化痰方通过LKB1/AMPK信号通路改善多囊卵巢综合征胰岛素抵抗的作用机制研究  

Study on mechanism of Jianpi Huatan Prescription in insulin resistance of polycystic ovary syndrome through AMPK/LKB1 signaling pathway

作　　者：罗甜 李潇 林安盈 杨璐瑜 李岚[4] 余曦明[5] Luo Tian;Li Xiao;Lin Anying;Yang Luyu;Li Lan;Yu Ximing(College of Pharmacy,Hunan University of Chinese Medicine,Changsha 410208,China;Women's Health and Rehabilitation Department,Guangzhou Huadu Maternal and Child Health Hospital,Guangzhou 510810,China;Obstetrics and Gynecology,Jiangxi Province Integrated Traditional Chinese and Western Medicine Hospital,Nanchang 330002,China;Department of Gynecology,the Second Affiliated Hospital of Hunan University of Chinese Medicine,Changsha 410005,China;Science and Technology Innovation Center,Hunan University of Chinese Medicine,Changsha 410208,China)

机构地区：[1]湖南中医药大学药学院,长沙410208 [2]广州市花都区妇幼保健院妇女保健与康复科,广州510810 [3]江西省中西医结合医院妇产科,南昌330002 [4]湖南中医药大学第二附属医院妇科,长沙410005 [5]湖南中医药大学科技创新中心,长沙410208

出　　处：《国际中医中药杂志》2024年第10期1303-1309,共7页International Journal of Traditional Chinese Medicine

基　　金：国家级大学生创新创业训练计划(202210541064)。

摘　　要：目的基于肝激酶B1(LKB1)/AMPK信号通路研究健脾化痰方对来曲唑联合高脂饲料诱导的PCOS伴胰岛素抵抗(IR)大鼠的影响,探讨其作用机制。方法将40只雌性SD大鼠分为造模组30只、空白组10只,造模组大鼠以高脂饲料喂养8周,从第4周起灌胃来曲唑溶液,连续5周;空白组正常饲养,第4周起灌胃等体积的羧甲基纤维素钠溶液。造模结束后,将造模组大鼠按随机数字表法分为健脾化痰方组、二甲双胍组、模型组,每组10只。健脾化痰方组和二甲双胍组予以相应药物干预,空白组和模型组灌胃等体积生理盐水,连续灌胃4周。采用HE染色观察卵巢组织形态学变化;腹腔葡萄糖耐量试验(IPGTT)检测大鼠糖耐量;ELISA法检测大鼠FSH、LH、雌二醇、睾酮、空腹血糖(FBG)、空腹胰岛素(FINS)水平;实时荧光定量PCR法和Western blot检测大鼠卵巢组织LKB1、AMPK mRNA及蛋白表达。结果与模型组比较,健脾化痰方组大鼠卵巢多囊样改变好转,体重降低(P<0.05),FBG、FINS、HOMA-IR、IPGTT水平降低(P<0.05或P<0.01);血清FSH、HDL-C水平升高(P<0.05或P<0.01),睾酮、LH、LH/FSH、TC、TG、LDL-C水平降低(P<0.05或P<0.01);卵巢组织中LKB1、AMPK mRNA及蛋白表达升高(P<0.05)。结论健脾化痰方可通过调控LKB1/AMPK信号通路,改善来曲唑联合高脂饲料导致的大鼠PCOS-IR,调节性激素水平,改善糖脂代谢紊乱状态,对大鼠卵巢多囊样变有修复作用。Objective To investigate the effects of Jianpi Huatan Prescription on a rat model of polycystic ovary syndrome(PCOS)with insulin resistance(IR)induced by letrozole combined with high fat diet based on the liver kinase B1(LKB1)/AMP activated protein kinase(AMPK)signaling pathway;To discuss its mechanism.Methods A total of 40 SD female rats were divided into model group(30 rats)and blank group(10 rats).The model group rats were fed with high-fat feed from the first week of modeling for 8 consecutive weeks,and from the fourth week onwards,were given a daily gavage of letrozole solution for 5 consecutive weeks;the blank group was fed normally,and from the 4th week onwards,an equal amount of sodium carboxymethyl cellulose solution was administered.After the completion of modeling,the modeling group was divided into Jianpi Huatan Prescription group,Metformin group,and model group according to random number table method.The Jianpi Huatan Prescription group and the metformin group were given corresponding drug interventions,while the other two groups were simultaneously administered an equal amount of physiological saline for a total of 4 weeks.Ovarian morphological changes were observed using HE staining;intraperitoneal glucose tolerance test(IPGTT)was used to detect glucose tolerance in rats;Enzyme linked immunosorbent assay(ELISA)was used to detect the levels of follicle stimulating hormone(FSH),luteinizing hormone(LH),estrogen(E2),total testosterone(T),fasting blood glucose(FBG),and fasting insulin(FINS)in rats;Real time fluorescence quantitative PCR and Western blot techniques were used to detect changes in LKB1,AMPK mRNA and protein expression in the LKB1/AMPK signaling pathway of rat ovarian tissue.Results Compared with the model group,the polycystic changes in the ovaries of rats in the Jianpi Huatan Prescription group were improved,and the growth rate of body weight decreased.The levels of FBG,FINS,HOMA-IR,and IPGTT decreased(P<0.05 or P<0.01),while serum FSH and HDL-C levels were significantly up-regulated(P<0.

关 键 词：多囊卵巢综合征 胰岛素抵抗 健脾化痰方 LKB1/AMPK 大鼠 

分 类 号：R285.5[医药卫生—中药学]