荷芪散对多囊卵巢综合征大鼠内分泌代谢及PI3 K/AKT信号通路的影响

摘要

目的 观察荷芪散对多囊卵巢综合征大鼠内分泌代谢的影响和对PI3K/AKT信号通路的调控作用,探讨荷芪散防治多囊卵巢综合征的可能作用机制.方法 从60只健康雌性SD中随机选取15只作为正常组,其余大鼠均采用颈背部皮下注射脱氢表雄酮(DHEA)的方法建立多囊卵巢综合征模型,将造模成功大鼠随机分为模型组、荷芪散组、二甲双胍组,每组15只.荷芪散组和二甲双胍组分别给予相应药物灌胃,正常组和模型组均给予生理盐水灌胃.灌胃8周后,检测各组大鼠血糖指标[空腹血糖(FPG)、空腹胰岛素(FINS)、胰岛素抵抗指数(HOMA-IR)]、血脂指标及性激素[黄体生成素(LH)、卵泡刺激素(FSH)、睾酮(T)]水平,同时用HE染色法观察各组大鼠卵巢组织形态,采用RT-PCR方法检测胰岛素受体底物-1(IRS-1)、丝氨酸/苏氨酸蛋白激酶AKT-2(AKT-2)、糖原合成激酶-3β(GSK-3β)、葡萄糖转运蛋白因子-4(GLUT-4)、人第10号染色体缺失的磷酸酶(PTEN)mRNA表达水平.结果 荷芪散组、二甲双胍组FPG、FINS、HOMA-IR、TC、TG、LDL-C、LH、LH/FSH、T均明显低于模型组(P均<0.05),而HDL-C变化不明显(P>0.05);荷芪散组FPG、FINS、HOMA-IR与二甲双胍组比较差异均无统计学意义(P均>0.05),TG、LDL-C、LH、LH/FSH、T均明显低于二甲双胍组(P均<0.05),而TC、FSH明显高于二甲双胍组(P均<0.05).荷芪散组、二甲双胍组大鼠卵巢组织接近正常.荷芪散组、二甲双胍组大鼠卵巢组织中IRS-1、AKT、GSK-3β、GLUT-4mRNA相对表达量均明显高于模型组(P均<0.05),PTENmRNA相对表达量均明显低于模型组(P均<0.05);荷芪散组大鼠卵巢组织中IRS-1、AKT、GSK-3β、GLUT-4mRNA相对表达量均明显高于二甲双胍组(P均<0.05),PTENmRNA相对表达量明显低于二甲双胍组(P<0.05).结论 荷芪散可通过上调局部卵巢组织PI3K/AKT信号通路中相关重要信号传导分子的基因表达,下调拮抗因子的基因表达,改善多囊卵巢综合征模型大鼠的糖脂代谢、胰岛素抵抗及卵巢组织形态.%Objective It is to observe the effects of Heqi San on endocrine metabolism and the regulation on PI 3K/AKT signaling pathway in rats with polycystic ovary syndrome (PCOS), and to explore its possible mechanism .Methods 60 healthy female SD rats were selected , in which 15 ones as normal group , the other rats were used to establish PCOS models by subcutaneous injection of dehydroepiandrosterone ( DHEA ) , the successful models were randomly divided into model group, Heqi San group and melbine group , each group had 15 rats.Heqi San group and melbine group were treated with respective medicine by gavage , the model group and normal group were given normal saline by gavage .After treatment for 8 weeks, the levels of blood sugar indexes (FPG, FINS, HOMA-IR), blood fat and sex hormone (LH, FSH, T) were de-tected, the morphological changes of ovarian tissue of rats were observed with HE staining method , and RT-PCR method was used to detect the expression of IRS -1,AKT-2,GSK-3B,GLUT-4,PTEN.Results The levels of FPG,FINS,HOMA-IR, TC, TG, LDL-C,LH, LH/FSH, T in Heqi san group and melbine group were significantly lower than that in model group (P<0.05), but the difference in HDL-C was not significant (P>0.05).The levels of TG, LDL-C,LH,LH/FSH, T in Heqi San group were lower while the levels of TC ,FSH were higher than those in melbine group (P<0.05), but there was no significant difference in FPG , FINS and HOMA-IR between the two groups (P>0.05).The ovary tissue was nearly normal in Heqi San group and melbine group .The expression of IRS-1, AKT, GSK-3B, GLUT-4mRNA in Heqi San group and melbine group were higher while the expression of PTEN mRNA was lower than those in model group (P<0.05).The expression of IRS-1, AKT, GSK-3B, GLUT-4mRNA in Heqi San group were higher while the expression of PTEN mRNA was lower than those in melbine group (P<0.05).Conclusion Heqi San can improve glucose and lipid metabolism , insu-lin resistance and ovarian morphology in the rats with PCOS by up-regulating the gene expression of related important signa-ling molecules and down-regulating antagonistic factor in via PI 3K/AKT pathway in local ovarian tissue .