绝经激素治疗对早发性卵巢功能不全患者氧化应激及免疫衰老的影响

Effect of menopausal hormone therapy on oxidative stress and immune aging in premature ovarian insufficiency

目的 探究绝经激素治疗(MHT)对早发性卵巢功能不全(POI)患者氧化应激及免疫衰老的影响。方法 选择2019年6月—2022年6月宁波大学附属第一医院收治的50例POI患者和50例健康围绝经期女性为研究对象,根据治疗方式分为A组(25例,健康围绝经期女性,安慰剂治疗)、B组(25例,健康围绝经期女性,MHT)、C组(25例,POI患者,安慰剂治疗)、D组(25例,POI患者,MHT)。对比4组治疗前后氧化应激指标、炎症细胞因子、免疫衰老指标及相关通路蛋白水平。结果 A组丙二醛(MDA)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSHPx)、过氧化氢酶(CAT)水平分别为(7.72±0.45)nmol/ml、(85.32±5.36)U/ml、(85.34±5.23)U/ml、(70.14±3.45)U/ml;B组MDA、SOD、GSHPx、CAT水平分别为(5.65±0.49)nmol/ml、(98.45±10.16)U/ml、(103.45±4.16)U/ml、(78.25±9.33)U/ml;C组MDA、SOD、GSHPx、CAT水平分别为(10.54±0.31)nmol/ml、(72.44±2.31)U/ml、(40.15±5.34)U/ml、(57.53±7.16)U/ml;D组MDA、SOD、GSHPx、CAT水平分别为(8.42±0.37)nmol/ml、(81.16±4.33)U/ml、(58.52±12.11)U/ml、(60.85±1.98)U/ml。4组MDA、SOD、GSHPx、CAT水平比较差异均有统计学意义(F=602.017,75.146,358.331,56.994,均P<0.05)。4组白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)水平,CD4^(+)/CD8^(+)比值、CD28^(+)/CD57^(+)比值、CD28^(-)/CD57^(-)比值、CD28^(-)/CD57^(+)比值,Keap1、Nrf2、NQO1蛋白水平比较,差异均有统计学意义(均P<0.05)。结论 MHT可降低POI患者炎症细胞因子水平,改善氧化应激损伤,降低免疫细胞的衰老程度,可能与激活Keap1-Nrf2/ARE信号通路有关。

Objective To investigate the effect of menopausal hormone therapy(MHT)on oxidative stress and immune aging of premature ovarian insufficiency(POI).Methods Fifty POI patients and fifty healthy perimenopausal women in the First Affiliated Hospital of Ningbo University from June 2019 to June 2022 were selected as study subjects.According to the treatment methods,they were divided into group A(25 healthy perimenopausal women receiving placebo treatment),group B(25 healthy perimenopausal women receiving MHT),group C(25 POI patients receiving placebo treatment),and group D(25 POI patients receiving MHT).The levels of oxidative stress indexes,inflammatory cytokines,immune senescence indexes,and related pathway proteins were compared among the four groups before and after treatment.Results The levels of malondialdehyde(MDA),superoxide dismutase(SOD),glutathione peroxidase(GSHPx),and catalase(CAT)in group A were(7.72±0.45)nmol/ml,(85.32±5.36)U/ml,(85.34±5.23)U/ml,and(70.14±3.45)U/ml,respectively;the levels of MDA,SOD,GSHPx,and CAT in group B were(5.65±0.49)nmol/ml,(98.45±10.16)U/ml,(103.45±4.16)U/ml,and(78.25±9.33)U/ml,respectively;the levels of MDA,SOD,GSHPx,and CAT in group C were(10.54±0.31)nmol/ml,(72.44±2.31)U/ml,(40.15±5.34)U/ml,and(57.53±7.16)U/ml,respectively;the levels of MDA,SOD,GSHPx,and CAT in group D were(8.42±0.37)nmol/ml,(81.16±4.33)U/ml,(58.52±12.11)U/ml,and(60.85±1.98)U/ml,respectively.There were statistically significant differences in the levels of MDA,SOD,GSHPx,and CAT among the four groups(F=602.017,75.146,358.331,56.994,all P<0.05).There were statistically significant differences in the levels of interleukin-6(IL-6),tumor necrosis factor-α(TNF^(-)α),CD4^(+)/CD8^(+)ratio,CD28^(+)/CD57^(+)ratio,CD28^(-)/CD57^(-)ratio,CD28^(-)/CD57^(+)ratio,Keap1,Nrf2,and NQO1 proteins among the four groups(all P<0.05).Conclusion MHT can reduce the levels of inflammatory cytokines,improve oxidative stress damage,and reduce aging degree of immune cells,which may be related to activation of Keap1-Nrf2/ARE signaling pathway.