人参皂苷Rg_(3)通过PI3K/Akt信号通路抑制大鼠卵巢型子宫内膜异位症血管生成相关因子表达机制研究  

Study on the Mechanism of Inhibiting Angiogenesis-related Factors Expression in Ovarian Endometriosis Rats by Ginsenoside Rg_(3)via P13K/Akt Signaling Pathway

作　　者：李晨阳 张学红[1] LI Chenyang;ZHANG Xuehong(First Clinical Medical College,Lanzhou University,Lanzhou 730000,China)

机构地区：[1]兰州大学第一临床医学院,甘肃兰州730000

出　　处：《西部中医药》2022年第11期66-72,共7页Western Journal of Traditional Chinese Medicine

基　　金：甘肃省自然科学基金(18JR3RA350/092NKDA009)。

摘　　要：目的:探讨人参皂苷Rg_(3)抑制卵巢型子宫内膜异位症(ovarian endometriosis,OEMs)大鼠血管生成相关因子表达及其机制。方法:采用异位移植的方法建造大鼠OEMs模型,给予人参皂苷Rg_(3)干预治疗,检测大鼠体质量;干预后采集大鼠卵巢型异位子宫,记录其体积和质量,利用定量聚合酶链反应(quantitative polymerase chain reaction,qPCR)法检测子宫血管内皮生长因子(vascular endothelial growth factor,VEGF)mRNA、血管内皮细胞生长因子受体2(vascular endothelial growth factor receptor 2,VEGFR-2)mRNA、缺氧诱导因子1α多肽(hypoxia-inducible factor 1-alpha,HIF-1α)mRNA、基质金属蛋白酶-9(matrix metalloproteinase-9,MMP-9)mRNA、基质金属蛋白酶-2(matrix metalloproteinase-2,MMP-2)mRNA的表达,蛋白印记Western blot和免疫组化法检测子宫磷脂酰肌醇-3-羟激酶(phosphatidylinositol 3-hydroxykinase,PI3K)、磷酸化磷脂酰肌醇-3-羟激酶(phosphorylated phosphatidylinositol 3-hydroxykinase,p-PI3K)、丝氨酸/苏氨酸蛋白激酶(serine/threonine protein kinase,Akt1)、磷酸化丝氨酸/苏氨酸蛋白激酶(serine/threonine protein kinase,p-Akt1)、细胞外调节蛋白激酶(extracellular regulated protein kinases,ERK1/2)、磷酸化细胞外调节蛋白激酶(phosphorylated extracellular regulated protein kinases,p-ERK1/2)蛋白。结果:人参皂苷Rg_(3)可浓度依赖性减缓子宫异位大鼠体质量下降幅度,降低异位子宫质量和体积,降低异位子宫组织中血管生成相关因子VEGF、VEGFR-2、HIF-1α、MMP-9、MMP-2的mRNA表达及蛋白表达和p-PI3K、p-Akt1、p-ERK1/2蛋白表达,对PI3K、Akt 1、ERK1/2总蛋白无影响。结论:人参皂苷Rg_(3)可抑制OEMs PI3K/Akt通路的激活,降低血管生成相关因子表达和ERK1/ERK2磷酸化水平,抑制OEMs血管生成。Objective:To discuss the inhibitory effects of ginsenoside Rg_(3)on the expressions of angiogenesis-related factors in ovarian endometriosis(OEMs)rats and its mechanism.Methods:Heterotopic transplantation was adopted to establish rat model with OEMs,and the models were intervened and treated with ginsenoside Rg_(3),to detect body mass of the rats;after the intervention,ovarian type ectopic uterus of the rats were collected to record the volume and mass,qPCR was used to determine the expressions of VEGF mRNA,VEGFR-2 mRNA,HIF-1αmRNA,MMP-9 mRNA and MMP-2 mRNA of the uterus,Western blot and immunohistochemical method were applied to measure P13K,p-P13K,Akt1,p-Akt1,ERK1/2,p-ERK1/2 protein in the womb.Results:Ginsenoside Rg_(3)could slow down the decrease of body mass of the rat model in a dose-dependent manner,reduce the mass and volume of ectopic uterus,lower the expressions of angiogenesis-related factors VEGF-2 mRNA,VEGFR mRNA,HIF-1αmRNA,MMP-9 mRNA and MMP-2 mRNA,and the contents of p-P13K,p-Akt1,p-ERK1/2 protein of the uterus,while it shows no influence on total protein of P13K,Akt1 and ERK1/2.Conclusion:Rg_(3)could inhibit the activation of P13K/Akt signaling pathway in OEMs rats,lower the expressions of angiogenesis-related factors and ERK1/ERK2 phosphorylation level,and refrain angiogenesis in OEMs.

关 键 词：子宫内膜异位症 卵巢型 PI3K/AKT信号通路 血管生成相关因子 人参皂苷RG3 

分 类 号：R271.19[医药卫生—中医妇科学]