文献类型：期刊文献

中文题名：基于PI3K/AKT信号通路研究当归水提物对多囊卵巢综合征大鼠的保护作用

英文题名：Protective Effect of Danggui(当归)Water Extract on Polycystic Ovary Syndrome Rats:Based on PI3K/AKT Signaling Pathway

作者：高雅[1,2];莫思懿[2];曹后康[2];张可锋[2];马晓辉[1];晋玲[1]

第一作者：高雅

机构：[1]甘肃中医药大学药学院,兰州730000;[2]桂林医学院高发病防治药理学重点实验室,桂林541004

第一机构：甘肃中医药大学药学院（西北中藏药协同创新中心办公室）

年份：2022

卷号：38

期号：6

起止页码：125

中文期刊名：中药药理与临床

外文期刊名：Pharmacology and Clinics of Chinese Materia Medica

收录：北大核心:【北大核心2020】；CSCD:【CSCD2021_2022】；

基金：国家自然科学基金(编号:81860673、81960779);道地药材生态种植及质量保障项目(编号:国中医药科技[2020]153号);国家现代农业产业技术体系项目(编号:CARS-21)。

语种：中文

中文关键词：当归水提物;多囊卵巢综合征(PCOS);糖脂代谢;磷酯酰肌醇3激酶/蛋白激酶信号通路

外文关键词：Danggui(当归)water extract;Polycystic ovary syndrome(PCOS);Glucose and lipid metabolism;PI3K/AKT signaling pathway

摘要：目的:研究当归水提物对来曲唑诱导的多囊卵巢综合征(PCOS)大鼠的保护作用及其作用机制。方法:将70只雌性SD大鼠随机选取15只设为正常对照组,每天灌胃1%羧甲纤维素钠溶液,其余55只大鼠作为造模组灌胃含有来曲唑1 mg/kg的1%羧甲纤维素钠溶液,灌胃体积均为8 mL/kg,同时给予高脂饲料喂养。4 w后,分别从正常对照组和造模组中随机挑选5只大鼠,对其卵巢进行病理学观察。确定造模成功后,将50只PCOS大鼠随机分为模型对照组、二甲双胍0.3 g/kg组、当归水提物2、4、8 g/kg组,每组10只。给药组灌胃给予相应的药物进行治疗,正常对照组和模型对照组给予等体积的蒸馏水,连续4 w。禁食不禁水16 h,麻醉大鼠后采集血液和卵巢,并记录卵巢质量;采用HE染色法评价大鼠卵巢组织病变;生化法或ELISA法测定血清中睾酮(T)、卵泡刺激素(FSH)、黄体生成素(LH)、雌二醇(E2)、空腹血糖(FBG)、空腹胰岛素(FINS)、三酰甘油(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)和高密度脂蛋白胆固醇(HDL-C)的活力或含量;Western blot法测定卵巢组织中磷酯酰肌醇-3激酶(PI3K)、p-PI3K、蛋白激酶B(AKT)和p-AKT的蛋白表达。结果:与正常对照组比较,模型对照组大鼠卵巢组织中颗粒细胞层数明显降低且囊状扩张明显,同时卵巢质量显著增加(P<0.01),血清T、LH、LH/FSH、FBG、FINS、HMOR-IR、TG、TC和LDL-C活力或含量均显著升高,且E2和HDL-C含量明显降低(P<0.01),卵巢组织中p-PI3K和p-AKT的蛋白表达显著下调(P<0.01);与模型对照组比较,当归水提物4、8 g/kg组卵巢组织颗粒细胞层数明显增加且囊状扩张得到改善,血清中T、LH、LH/FSH、FBG、FINS、HMOR-IR、TG、TC和LDL-C活力或含量均明显降低(P<0.05或P<0.01),E2和HDL-C含量显著上升(P<0.01),卵巢组织p-PI3K和p-AKT蛋白相对表达显著上调(P<0.05或P<0.01)。结论:当归水提物能缓解来曲唑导致的大鼠PCOS,并调节糖脂代谢紊乱,且作用机制可能与调控PI3K/AKT信号通路有关。
Objective:To study the effect and mechanism of Danggui(当归)water extract against letrozole-induced polycystic ovary syndrome(PCOS)in rats.Methods:Among 70 female SD rats,15 were randomly selected as the normal control group and were given 1%carboxymethylcellulose sodium solution(ig)every day.The remaining 55 rats were given 1%carboxymethylcellulose sodium solution containing 1 mg/kg letrozole(8 mL/kg,ig)for modeling and fed with high-fat diet at the same time.After 4 weeks,5 rats were randomly selected from the normal control group and the modeling group,respectively,and pathological changes of their ovaries were observed.After the identification of modeling outcome,50 PCOS rats were randomized into the model control group,0.3 g/kg metformin group,and 2 g/kg,4 g/kg,and 8 g/kg Danggui water extract groups,with 10 rats in each group.Rats in the administration groups were treated with corresponding drugs and those in the normal control group and model control group were given equivalent volume of distilled water for 4 consecutive weeks.After fasting for 16 h,blood and ovaries were collected from anesthetized rats,and the mass of ovaries was recorded.Based on hematoxylin-eosin(HE)staining,pathological changes of rat ovarian tissues were evaluated.Biochemical methods or enzyme-linked immunosorbent assay(ELISA)were employed to determine the activities or content of serum testosterone(T),follicle-stimulating hormone(FSH),luteinizing hormone(LH),estradiol(E2),fasting blood glucose(FBG),fasting insulin(FINS),triglycerides(TG),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C),and high-density lipoprotein cholesterol(HDL-C).Western blotting was used to determine the protein expression of phosphatidylinositol-3 kinase(PI3 K),phosphorylated phosphatidylinositol-3 kinase(p-PI3 K),protein kinase B(AKT),and phosphorylated protein kinase B(p-AKT).Results:Compared with the normal control group,the model control group showed small number of granulosa cells in the ovarian tissue,obvious cystic dilatation,and high ovary mass(P<0.01).The activities or content of T,LH,LH/FSH,FBG,FINS,HMOR-IR,TG,TC,and LDL-C in serum were increased,and the serum content of E2 and HDL-C(P<0.01)and protein expression of p-PI3 K and p-AKT in ovarian tissue were down-regulated(P<0.01)in the model control group as compared with those in the normal control group.Compared with the model control group,4 g/kg and 8 g/kg Danggui water extract decreased the number of granulosa cells in ovarian tissue,alleviated the cystic dilatation,lowered the activities or content of serum T,LH,LH/FSH,FBG,FINS,HMOR-IR,TG,TC,and LDL-C(P<0.05 or P<0.01),and up-regulated the content of E2 and HDL-C(P<0.01)and the relative protein expression of p-PI3 K and p-AKT in ovarian tissue(P<0.05 or P<0.01).Conclusion:Danggui water extract can relieve letrozole-induced PCOS in rats and alleviate the metabolic disorder of glucose and lipids by regulating the PI3 K/AKT signaling pathway.