基于PI3K/Akt/mTOR信号通路探讨他克莫司联合多西环素对慢性子宫内膜炎的疗效及机制

Investigation of the efficacy and mechanism of tacrolimus combined with Doxycycline in the treatment of chronic endometritis via the PI3K/Akt/mTOR signaling pathway

摘要:

目的 基于PI3K/Akt/mTOR信号通路探讨他克莫司联合多西环素对慢性子宫内膜炎的疗效及其潜在机制。方法 选取2021年1月—2023年1月邯郸市第一医院妇科诊治的慢性子宫内膜炎患者94例，按照掷硬币法分为对照组和观察组，各47例。对照组采用多西环素治疗，观察组采用他克莫司联合多西环素治疗。比较两组的临床疗效，治疗前后PI3K、Akt、mTOR mRNA表达，血清PI3K/Akt/mTOR相关炎症因子［白细胞介素-1β（IL-1β）、肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）、干扰素-γ（IFN-γ）、白细胞介素-10（IL-10）］水平，外周血T细胞亚群（CD4⁺、CD8⁺、CD4⁺/CD8⁺）水平，治疗后随访12个月的复发率及不良反应发生率。结果 观察组总有效率高于对照组（P <0.05）。观察组治疗前后PI3K、Akt、mTOR mRNA相对表达量的差值均高于对照组（P <0.05）。观察组治疗前后IL-1β、TNF-α、IL-6、IFN-γ、IL-10水平的差值均高于对照组（P <0.05）；治疗后，两组患者的IL-1β、TNF-α、IL-6、IFN-γ水平均显著下降，IL-10水平显著升高，且观察组的IL-1β、TNF-α、IL-6、IFN-γ水平低于对照组，IL-10水平高于对照组（P <0.05）。两组治疗前后CD4⁺T的差值比较，经t检验，差异有统计学意义（P<0.05）；两组治疗前后CD8⁺T细胞和CD4⁺/CD8⁺比值的差值比较，差异均无统计学意义（P >0.05）。观察组CD38、CD138阳性率均低于对照组（P <0.05）。随访12个月，观察组有10例患者（21.28%）复发，对照组有15例患者（31.91%）复发，两组复发率比较，差异无统计学意义（P >0.05）。观察组不良反应总发生率低于对照组（P <0.05）。结论 他克莫司联合多西环素治疗慢性子宫内膜炎的疗效显著，降低复发风险，其机制可能与调控PI3K/Akt/mTOR信号通路，抑制炎症反应及改善免疫功能有关。

Abstract:

Objective To evaluate the efficacy of tacrolimus-doxycycline combination therapy for chronic endometritis (CE) and explore its mechanisms through PI3K/Akt/mTOR signaling pathway modulation.Methods Ninety-four CE patients treated at our hospital (January 2021-January 2023) were randomly assigned to either doxycycline monotherapy (control group, n = 47) or tacrolimus-doxycycline combination therapy (observation group, n = 47). Outcomes included: clinical efficacy; PI3K/Akt/mTOR mRNA expression; serum inflammatory cytokines [IL-1β, TNF-α, IL-6, IFN-γ, IL-10]; T-cell subsets (CD4?, CD8?, CD4?/CD8? ratio); 12-month recurrence rate; and adverse events.Results The observation group demonstrated significantly higher overall efficacy (P < 0.05) and greater reductions in PI3K, Akt, and mTOR mRNA expression (P < 0.05). Combination therapy yielded significantly larger decreases in proinflammatory cytokines (IL-1β, TNF-α, IL-6, IFN-γ) and greater IL-10 elevation vs. monotherapy (P < 0.05). Post-treatment, observation group showed: Significantly lower IL-1β, TNF-α, IL-6, IFN-γ concentrations (P < 0.05); Higher IL-10 levels (P < 0.05); Greater CD4? T-cell increase (P < 0.05); and Reduced CD38? and CD138? plasma cell positivity (P < 0.05). No significant intergroup differences were observed in CD8? T-cells, CD4?/CD8? ratio, or 12-month recurrence rate (21.28% vs. 31.91%, P > 0.05). The adverse event incidence was significantly lower with combination therapy (P < 0.05).Conclusion Tacrolimus-doxycycline combination therapy significantly improves CE outcomes by modulating PI3K/Akt/mTOR signaling, attenuating inflammation, enhancing CD4? T-cell response, and reducing plasma cell infiltration, with favorable safety profile.