健脾化痰方通过调控FOXO1/PDK4信号通路干预PCOS-IR大鼠脂代谢的作用机制研究OA北大核心CSTPCD
Effects of Jianpi Huatan Fang on lipid metabolism and FOXO1/PDK4 expression in the ovary in rats with polycystic ovary syndrome and insulin resistance
目的 探讨健脾化痰方对多囊卵巢综合征合并胰岛素抵抗(PCOS-IR)大鼠脂代谢及叉头盒转录因子-1(FOXO1)/丙酮酸脱氢酶激酶 4(PDK4)信号通路的影响.方法 40 只雌性SD大鼠随机分为空白对照组 10只和造模组 30 只.采用高脂饮食(8 周)联合来曲唑(第 4～8 周加入)建立PCOS-IR大鼠模型.完成造模后,将造模组大鼠随机分为模型对照组、健脾化痰方组、二甲双胍组,药物干预 4 周.观察各组一般情况,测定中医证候评分,计算体重变化;采用苏木素-伊红(HE)染色观察卵巢组织病理学改变;血液生化仪测定空腹血糖(FBG)和血脂四项;酶联免疫吸附(ELISA)法测定性激素如卵泡刺激素(FSH)、促黄体生成素(LH)、睾酮(T)、雌激素(E2)、胰岛素(FINS)水平;蛋白免疫印迹(Western Blot)法及实时荧光定量PCR法测定卵巢FOXO1、PDK4 表达的变化.结果 与空白对照组相比,模型对照组出现脾虚痰湿症状,体重明显增加,血清LH、T、LH/FSH升高,E2、FSH降低,卵巢多囊性改变明显,糖脂代谢调控失常(P＜0.01).与模型对照组相比,健脾化痰方组与二甲双胍组大鼠体重增速放缓,卵泡发育情况见好,血清LH、T、LH/FSH、FBG、FINS、HOMA-IR、TC、TG、LDL-C降低,E2、FSH升高,卵巢FOXO1、PDK4 mRNA及蛋白表达下调(P＜0.05,P＜0.01);可升高血清HDL-C含量,但是组间差别无统计学意义(P＞0.05).结论 健脾化痰方能有效调节性激素分泌,改善PCOS-IR大鼠卵巢生殖功能,调节糖脂代谢,其机制可能是通过抑制FOXO1/PDK4 通路发挥作用.
Objective To investigate the effects of Jianpi Huatan Fang on lipid metabolism and expression levels of FOXO1 and PDK4 in rats with polycystic ovary syndrome(PCOS)and insulin resistance(IR).Methods Forty female rats were divided randomly into a blank control group(n=10)and a model group(n=30).A PCOS-IR rat model was established using a high-fat diet(8 weeks)combined with letrozole(added at weeks 4～8).Thirty successfully modeled rats were then divided randomly into a model control group,a Jianpi Huatan Fang group(11.07 g/kg),and a metformin group(0.2 g/kg)(n=10 rats per group).Drug intervention was given for 4 weeks.The general status,Traditional Chinese medicine syndrome score,and weight changes were observed in each group.Histopathological changes in the ovary were detected by hematoxylin and eosin staining.Fasting blood glucose and blood lipids were measured using a blood biochemical analyzer.Levels of sex hormones including follicle-stimulating hormone(FSH),luteinizing hormone(LH),testosterone(T),estradiol(E2),and insulin were determined by enzyme linked immunosorbent assay and changes in the expression of FOXO1 and PDK4 in the ovaries were determined by Western Blot and real-time fluorescence quantitative polymerase chain reaction.Results Rats in the model control group exhibited symptoms of spleen deficiency and phlegm-dampness and showed significant weight gain,sex hormone disorders,polycystic ovarian changes,and dysregulation of glucose and lipid metabolism,compared with rats in the blank control group(P＜0.01).In addition,weight increase was slower in rats in the Jianpi Huatan Fang group and the metformin group compared with that in the model control group,and follicle development was improved.Serum LH,T,LH/FSH,fasting blood glucose,insulin,homeostatic model assessment for IR,cholesterol,triglycerides,and low-density lipoprotein cholesterol decreased,estradiol and FSH increased,and ovarian FOXO1 and PDK4 mRNA and protein expression levels were down regulated in the Jianpi Huatan Fang group compared with the findings in the model control group(P＜0.05,P＜0.01).Serum high-density lipoprotein cholesterol content was also increased,but the difference was not significant(P＞0.05).Conclusions Jianpi Huatan Fang can effectively regulate sex hormone secretion,improve ovarian reproductive function,and regulate glucose and lipid metabolism in obese PCOS-IR rats,possibly via inhibiting the FOXO1/PDK4 pathway.
杨璐瑜;林安盈;杨正望;李岚;余曦明
湖南中医药大学第一附属医院,长沙 410021湖南中医药大学,长沙 410208湖南中医药大学第二附属医院,长沙 410005
生物学
多囊卵巢综合征胰岛素抵抗脂代谢FOXO1PDK4健脾化痰方
polycystic ovary syndromeinsulin resistancelipid metabolismFOXO1PDK4Jianpi Huatan Fang
《中国实验动物学报》 2024 (004)
451-460 / 10
湖南省自然科学基金青年项目(2022JJ40317),湖南中医药大学中药粉体与创新药物省部共建国家重点实验室培育基地开放基金(21PTKF1011). Funded by the Hunan Natural Science Foundation Youth Program(2022JJ40317),Open Fund for the Cultivation Base of State Key Laboratory of Traditional Chinese Medicine Powder and Innovative Drugs Jointly Built by Hunan University of Chinese Medicine(21PTKF011).
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