文献类型：期刊文献

中文题名：基于PTEN介导的PI3K/AKT信号通路探讨加味四君子汤干预卵巢早衰的作用机制

英文题名：Exploration on the Mechanism of Intervention of Modified Sijunzi Decoction in Premature Ovarian Failure Based on PI3K/AKT Signaling Pathway Mediated by PTEN

作者：代雅婷[1];李晶[1];桑玉莹[1];辛如娟[1];魏冬青[2];王新斌[3]

第一作者：代雅婷

机构：[1]甘肃中医药大学中西医结合学院,甘肃兰州730000;[2]甘肃中医药大学附属医院,甘肃兰州730000;[3]甘肃中医药大学,甘肃兰州730000

第一机构：甘肃中医药大学中西医结合学院

年份：2025

卷号：32

期号：11

起止页码：77

中文期刊名：中国中医药信息杂志

外文期刊名：Chinese Journal of Information on Traditional Chinese Medicine

基金：甘肃省自然科学基金(23JRRA1206);甘肃省高校教师创新基金项目(2023B-109)。

语种：中文

中文关键词：加味四君子汤;卵巢早衰;磷酸酶与张力蛋白同源物;磷脂酰肌醇3-激酶;蛋白激酶B;大鼠

外文关键词：modified Sijunzi Decoction;premature ovarian failure;PTEN;PI3K;AKT;rats

摘要：目的探讨加味四君子汤通过PTEN介导的PI3K/AKT信号通路干预卵巢早衰(POF)的作用机制。方法将50只SPF级健康雌性SD大鼠分为正常组(10只)和造模组(40只),造模组予环磷酰胺注射构建POF模型,将造模组随机分为模型组和中药低、中、高剂量组,每组10只,中药低、中、高剂量组予加味四君子汤药液6.3、12.6、25.2 g/kg灌胃,正常组和模型组予等体积生理盐水灌胃,每日1次,连续28 d。每日观察并记录大鼠一般状态,给药结束后测定卵巢指数,HE染色观察卵巢组织形态,ELISA检测血清雌二醇(E_(2))、黄体生成素(LH)、卵泡刺激素(FSH)、抗米勒管激素(AMH)、促性腺激素释放激素(GnRH)、β-内啡肽(β-EP)含量,RT-PCR检测卵巢组织磷酸酶与张力蛋白同源物(PTEN)、磷脂酰肌醇3-激酶(PI3K)、蛋白激酶B(AKT)mRNA表达,Western blot检测PTEN、PI3K、AKT、p-PI3K、p-AKT蛋白表达,免疫组化检测PTEN、PI3K、AKT阳性表达。结果与正常组比较,模型组大鼠精神萎靡,毛发脱落,饮食饮水减少,大便变稀,体质量减少(P<0.05),卵巢指数降低(P<0.05),卵巢组织结构紊乱,卵泡数量减少,血清LH、FSH、GnRH含量升高(P<0.05),E_(2)、AMH、β-EP含量降低(P<0.05),卵巢组织PTEN mRNA及蛋白表达降低(P<0.05),PI3K、AKT mRNA及蛋白表达升高(P<0.05),p-PI3K、p-AKT蛋白表达升高(P<0.05);与模型组比较,中药各剂量组大鼠一般状态较前明显改善,体质量增加(P<0.05),卵巢指数升高(P<0.05),卵巢组织成熟卵泡数量增加,血清LH、FSH、GnRH含量降低(P<0.05),E_(2)、AMH、β-EP含量升高(P<0.05),卵巢组织PTEN mRNA及蛋白表达升高(P<0.05),PI3K、AKT mRNA及蛋白表达降低(P<0.05),p-PI3K、p-AKT蛋白表达降低(P<0.05)。结论加味四君子汤可能通过调控PTEN介导的PI3K/AKT信号通路,修复POF大鼠卵巢组织卵泡过度消耗,改善卵巢功能,从而达到干预POF进程的目的。
Objective To explore the mechanism of modified Sijunzi Decoction in the intervention of premature ovarian failure(POF)rats through PTEN-mediated PI3K/AKT signaling pathway.Methods Totally 50 SPF-grade healthy female SD rats were divided into normal group(10 rats)and model group(40 rats).The model group was injected with cyclophosphamide to establish a POF model,and then randomly divided into model group and TCM low-,medium-and high-dosage group,with 10 rats in each group,TCM low-,medium-and high-dosage group were given modified Sijunzi Decoction 6.3,12.6,25.2 g/kg by gavage,the normal group and model group were given equal volume of normal saline,once a day for 28 days.The general condition and body mass of rats in each group were observed and recorded daily.After administration,the ovarian index was measured,HE staining was used to observe the morphology of ovarian tissue,ELISA was used to detect the contents of serum estradiol(E2)luteinizing hormone(LH),follicle-stimulating hormone(FSH),anti-Müllerian hormone(AMH),gonadotropin-releasing hormone(GnRH)andβ-endorphin(β-EP),RT-PCR was used to detect the mRNA expression of PTEN,PI3K and AKT in ovarian tissue,Western blot was used to detect the protein expression of PTEN,PI3K,AKT,p-PI3K and p-AKT,immunohistochemistry was used to detect the positive expression of PTEN,PI3K and AKT.Results Compared with the normal group,the rats in the model group were depressed,the hair fell off,the diet and drinking water were reduced,the stools became thinner,the body mass was reduced(P<0.05),and the ovarian index was reduced(P<0.05),the ovarian tissue structure was disordered,the number of follicles decreased,and the contents of serum LH,FSH and GnRH increased(P<0.05),the contents of E2,AMH andβ-EP decreased(P<0.05),the expression of PTEN mRNA and protein decreased(P<0.05),the expressions of PI3K and AKT mRNA and protein increased(P<0.05),and the expressions of p-PI3K and p-AKT protein increased(P<0.05).Compared with the model group,the general condition of rats in each dosage of TCM groups improved significantly,the body mass increased(P<0.05),ovarian index increased(P<0.05),the number of follicles in rat ovarian tissue increased,the contents of LH,FSH and GnRH decreased(P<0.05),the contents of E2,AMH andβ-EP increased(P<0.05),the expression of PTEN mRNA and protein increased(P<0.05),the expression of PI3K and AKT mRNA and protein decreased(P<0.05),and the protein expression of p-PI3K and p-AKT decreased(P<0.05).Conclusion Modified Sijunzi Decoction may regulate the PI3K/AKT signaling pathway mediated by PTEN,repair the excessive consumption of follicles in ovarian tissue of POF rats,improve the ovarian function,so as to intervene the process of POF.