r-hGH联合DHEA对卵巢低反应小鼠GDF-9、AGE、RAGE表达的影响

Effects of r-hGH combined with DHEA on the expression of GDF-9,AGE and RAGE in ovarian hyporesponsiveness mice

目的 探究重组人生长激素(r-hGH)联合脱氢表雄酮(DHEA)对卵巢低反应(POR)小鼠模型干预效果及对生长分化因子-9(GDF-9)、晚期糖基化终末产物(AGE)及其受体(RAGE)的影响。方法 100只小鼠随机分为对照组、模型组、r-hGH组、DHEA组和r-hGH+DHEA组。使用慢性制动应激法建立卵巢早衰及卵巢低反应小鼠模型,对照组用等量的溶剂处理。r-hGH组和DHEA组分别使用r-hGH和DHEA干预,r-hGH+DHEA组进行联合干预。检测血清抗苗勒管激素(AMH)水平。使用HE染色法检测卵巢中卵泡数量。qRT-PCR和Western blotting检测卵巢组织中AGE、RAGE和卵泡中GDF-9 mRNA和蛋白水平。结果 建模后,小鼠血清AMH、卵泡数目以及GDF-9 mRNA和蛋白水平降低,而AGE、RAGE mRNA和蛋白水平升高(P<0.05)。r-hGH组和DHEA组的AMH、卵泡数目以及GDF-9 mRNA和蛋白水平高于模型组,而AGE、RAGE mRNA和蛋白水平低于模型组(P<0.05)。r-hGH+DHEA组AMH、卵泡数目以及GDF-9 mRNA和蛋白水平高于r-hGH组和DHEA组,而AGE、RAGE mRNA和蛋白水平低于r-hGH组和DHEA组(P<0.05)。结论 r-hGH联合DHEA对POR小鼠具有较好干预效果,与下调卵巢中AGE、RAGE并促进GDF-9 mRNA和蛋白的表达有关。

Aim To investigate the effect of recombinant human growth hormone(r-hGH)combined with de-hydroepiandrosterone(DHEA)on the ovarian hyporesponsive mouse model and its effect on the expression ofgrowth differ-entiation factor-9(GDF-9),advanced glycation end product(AGE)and receptor of advanced glycation endproducts(RAGE).Methods:100 mice were randomly divided into control group,model group,r-hGH group,DHEA group and r-hGH+DHEA group.A model of premature ovarian failure and ovarian hyporesponsiveness was established using chronic brake stress.The control group was treated with the same amount of solvent.The r-hGH group and DHEA group were treated with r-hGH and DHEA respectively.The mice in the r-hGH+DHEA group were treated with r-hGH and DHEA.The level of anti-Mullerian hormone(AMH)in the serum was measured.The number of follicles in the ovary was measured using HE staining.qRT-PCR and Western blotting were used to detect the levels of AGE,RAGE GDF-9 mRNA and protein in follicles in ovarian tissue.Results:After modeling,mouse serum AMH,follicle number,AGE,RAGE and GDF-9 mRNA and protein levels were significantly reduced(P<0.05).The AMH,follicle number,AGE,RAGE,and GDF-9 mRNA and protein levelsin the r-hGH group and DHEA group were significantly higher than those in the model group(P<0.05).The AMH,follicle number,AGE,RAGE,and GDF-9 mRNA and protein levels in the r-hGH+DHEA group were significantly higher than those in the r-hGH and DHEA groups(P<0.05).Conclusion R-hGH combined with DHEA has a good intervention effect on POR mouse model,which may be related to its down-regula-tion of AGE and RAGE mRNA levels in ovary and promotion of GDF-9 expression.