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
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湖南中医药大学

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湖南省自然科学基金青年项目


Mechanism of Jianpi Huatan Fang in Intervention of Lipid Metabolism in PCOS-IR Rats by Regulating FOXO1/PDK4 Signal Pathway
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Hunan University of Chinese Medicine

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    摘要:

    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:50只雌性大鼠随机分为空白对照组10只和造模组40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,通过HOMA-IR、卵巢组织病理观察评估模型。将造模成功的30只大鼠随机分为模型对照组、健脾化痰方组(11.07g/kg)、二甲双胍组(0.2g/kg),每组各10只,药物干预4周。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(甘油三酯TG、胆固醇TC、高密度脂蛋白HDL-C、低密度脂蛋白LDL-C);酶联免疫吸附(ELISA)法测定性激素(卵泡刺激素FSH、促黄体生成素LH、睾酮T)、胰岛素(FINS)水平;免疫蛋白印迹(WB)法及实时荧光定量PCR法测定卵巢FOXO1、PDK4表达的变化。结果:与空白对照组比较,模型对照组体重明显增加,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,可能是通过抑制FOXO1/PDK4通路发挥作用。

    Abstract:

    Objective: To investigate the effects of Jianpi Huatan recipe on lipid metabolism and expression of FOXO1 and PDK4 in rats with polycystic ovary syndrome (PCOS) and insulin resistance (IR) . Methods: Fifty female rats were randomly divided into a blank control group of 10 and a model group of 40. A PCOS-IR rat model was established using a high-fat diet (8 weeks) combined with letrozole (added at weeks 4-8), and the model was evaluated through HOMA-IR and ovarian tissue pathology observation. Thirty successfully modeled rats were randomly divided into a model control group, a Jianpi Huatan Fang group (11.07g/kg), and a Metformin group (0.2g/kg), with 10 rats in each group. Drug intervention was given for 4 weeks. Hematoxylin eosin (HE) staining was used to observe the histopathology changes of the ovary; Fasting blood glucose (FBG) and blood lipids (triglyceride TG, cholesterol (TC), high-density lipoprotein (HDL-C), low-density lipoprotein (LDL-C) were measured by blood biochemical analyzer; Enzyme linked immunosorbent assay (ELISA) was used to measure the levels of sex hormones follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T) and insulin (FINS); Immunoblotting (WB) and real-time fluorescence quantitative PCR were used to detect changes in the expression of FOXO1 and PDK4 in the ovaries. Results: Compared with the blank control group, the model control group showed significant weight gain, significant polycystic ovarian changes, and dysregulation of glucose and lipid metabolism (P<0.01). Compared with the model control group, the weight growth rate of rats in the Jianpi Huatan Fang group slowed down, and the development of follicles improved. Serum LH, T, LH/FSH, FBG, FINS, HOMA-IR, TC, TG, LDL-C decreased, E2 and FSH increased, while ovarian FOXO1, PDK4 mRNA and protein expression were down regulated (P<0.05, P<0.01); It can increase the serum HDL-C content, but there is no statistically significant difference between groups (P>0.05). Conclusion:Jianpi Huatan recipe can effectively regulate the secretion of sex hormones, improve the ovarian reproductive function and regulate glucose and lipid metabolism in obese PCOS-IR rats, which may play a role by inhibiting FOXO1/PDK4 pathway.

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  • 收稿日期:2023-08-13
  • 最后修改日期:2024-03-20
  • 录用日期:2024-03-20
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