Panevina A S, Smetneva N S, Vasilenko A M, Shestakova M V
Endocrinology Research Centre, Moscow, Russia.
A.I. Evdokimov Moscow State University of Medicine and Dentistry, Moscow, Russia.
Ter Arkh. 2018 Nov 22;90(10):79-83. doi: 10.26442/terarkh2018901079-83.
To determine the effects of menopausal hormone therapy dosage on levels of proinflammatory cytokines and immunoglobulins in bodily fluids of patients with type 2 diabetes mellitus (DM) and chronic obstructive pulmonary disease (COPD) during perimenopause.
The study included 119 perimenopausal females with moderate type 2 DM and stable COPD with signs of menopausal syndrome. Cytokine levels in bronchoalveolar lavage fluid and blood serum were measured with flow cytofluorometry (Вeckman Coulter FC500, USA) using a multiplex kit for human cytokines (BMS810FF) in adherence to the manufacturer's instructions. The lower limit of quantification was 2.5-52.7 pg/mL. The following cytokines were studied: IL-1β, IL-6, IL-8, TNF-α and IF-γ. The data was analyzed with Flow CytomixProver 3.0 manufacturer-licensed software package. IgМ, IgG and IgА in the blood serum (Vektor-Best, Russia) were detected using an immunoenzymatic assay (Stat Fax 3200Analyzer, Awareness Technology, USA). Menopausal hormone therapy (MHT) with 17 beta-estradiol/dydrogesterone (standard - 2 mg, low - 1 mg, ultralow - 0.5 mg): 0.5/2.5 (estradiol 0.5 mg/dydrogesterone 2.5 mg) - ultralow-dose MHT, 1/10 (estradiol 1 mg/dydrogesterone 10 mg) - low-dose MHT; 2/10 (estradiol 2 mg/dydrogesterone 10 mg) - standard-dose MHT. Саrbohydrate metabolism was assessed in three groups.
While 2/10 MHT yielded the most prominent decrease in IL-1β, IL-6, IL-8, TNF-α and IF-γ levels in bronchoalveolar lavage fluid and blood serum, the effect was statistically insignificant compared to 0.5/2.5 and 1/10 MHT. Initially decreased IgM, IgG and IgA levels were elevated in all the three dosage groups with no significant differences between them. As to carbohydrate metabolism target values of glycemia were achieved in all three groups taking MHT.
Standard-, low- and ultralow-dose MHT has positive effects on levels of proinflammatory cytokines and immunoglobulins characteristic of the association between type 2 DM, COPD and menopausal syndrome. The differences between the three dosage groups were statistically insignificant. Different dosage of MHT with dydrogesterone provide for improving impaired carbohydrate metabolism.
确定围绝经期2型糖尿病（DM）和慢性阻塞性肺疾病（COPD）患者接受绝经激素治疗的剂量对其体液中促炎细胞因子和免疫球蛋白水平的影响。
该研究纳入了119名患有中度2型DM且COPD病情稳定并有绝经综合征体征的围绝经期女性。支气管肺泡灌洗液和血清中的细胞因子水平采用流式细胞荧光测定法（美国贝克曼库尔特FC500），使用人细胞因子多重检测试剂盒（BMS810FF），按照制造商的说明进行测定。定量下限为2.5 - 52.7 pg/mL。研究了以下细胞因子：白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）、白细胞介素-8（IL-8）、肿瘤坏死因子-α（TNF-α）和干扰素-γ（IF-γ）。数据使用制造商授权的Flow CytomixProver 3.0软件包进行分析。血清中的免疫球蛋白M（IgМ）、免疫球蛋白G（IgG）和免疫球蛋白A（IgА）（俄罗斯Vector-Best公司产品）采用免疫酶测定法（美国Aware Technology公司Stat Fax 3200分析仪）进行检测。采用17β-雌二醇/地屈孕酮进行绝经激素治疗（MHT）（标准剂量 - 2 mg，低剂量 - 1 mg，超低剂量 - 0.5 mg）：0.5/2.5（雌二醇0.5 mg/地屈孕酮2.5 mg） - 超低剂量MHT，1/10（雌二醇1 mg/地屈孕酮10 mg） - 低剂量MHT；2/10（雌二醇2 mg/地屈孕酮10 mg） - 标准剂量MHT。对三组的碳水化合物代谢情况进行了评估。
虽然2/10剂量的MHT使支气管肺泡灌洗液和血清中IL-1β、IL-6、IL-8、TNF-α和IF-γ水平下降最为显著，但与0.5/2.5和1/10剂量的MHT相比，该效果在统计学上无显著差异。所有三个剂量组中，最初降低的IgM、IgG和IgA水平均有所升高，且组间无显著差异。至于碳水化合物代谢，所有接受MHT的三组患者的血糖目标值均已达到。
标准剂量、低剂量和超低剂量的MHT对2型DM、COPD与绝经综合征关联所特有的促炎细胞因子和免疫球蛋白水平具有积极影响。三个剂量组之间的差异在统计学上不显著。不同剂量的地屈孕酮MHT可改善受损的碳水化合物代谢。
