胸段硬膜外阻滞改善老年食管癌患者术后免疫抑制的机制

Mechanism of thoracic epidural block in improvement of immunosuppression after esophageal cancer surgery in elderly patients

目的探讨胸段硬膜外阻滞对老年食管癌患者术后免疫功能的影响。方法选取40例65岁以上行右胸上腹两切口食管癌根治术患者,随机分为全身麻醉组(GA组)和全身麻醉复合胸段硬膜外阻滞组(GEA组)。检测术前、术后48 h受试者血清中肿瘤坏死因子-α(TNF-α)、白介素-2(IL-2)、白介素-10(IL-10),外周血单个核细胞(PBMC)程序性细胞死亡蛋白-1配体(PD-L1)及CD8^+T细胞程序性细胞死亡蛋白-1(PD-1)表达量,CD8^+T细胞凋亡率,以及CD8^+T细胞分泌γ-干扰素(IFN-γ)的能力。结果 2组术后48 h TNF-α、IL-2、IL-10水平均高于术前,其中GEA组TNF-α、IL-2、IL-10水平显著低于GA组(P<0.05)。2组术前PD-L1表达量、PD-1含量、CD8^+T细胞凋亡率、IFN-γ无显著差异(P>0.05),术后48 h GEA组PBMC PD-L1表达量显著低于GA组(P<0.05)、CD8^+T细胞PD-1表达显著高于GA组(P<0.05),CD8^+T细胞凋亡率显著低于GA组(P<0.05),但CD8^+T细胞分泌IFN-γ水平显著高于GA组(P<0.05)。结论胸段硬膜外阻滞可能通过降低围术期的应激反应来部分逆转围术期单核细胞PD-L1的上调,从而减轻T细胞IFN-γ的分泌和增殖的抑制,改善老年食管癌患者围术期免疫功能。

Objective To investigate effect of thoracic epidural block on postoperative immunologic function in elderly esophageal cancer patients. Methods Forty esophageal cancer patients over 65 years of age underwent two incisions in the upper right thoracic abdomen were selected and randomly divided into two groups： general anesthesia group（ GA group） and general anesthesia combined with thoracic epidural block group（ GEA group）. Preoperative and postoperative 48 h serum tumor necrosis factor-α（ TNF-α）,interleukin-2（ IL-2）,interleukin-10（ IL-10） levels were determined,expression levels of programmed cell death protein-1 ligand（ PD-L1） in peripheral blood mononuclear cells（ PBMCs） and programmed cell death protein-1（ PD-1） in CD8^＋T cells were detected. CD8^＋T cell apoptosis rate and CD8^＋T cell IFN-γ secretion ability were detected. Results After 48 h of operation,the levels of TNF-α,IL-2 and IL-10 in both groups were higher than surgery before,and GEA group was significantly lower than GA group（ P〈0. 05）. PD-L1 expression,PD-1 content,CD8^＋T cell apoptosis rate,and IFN-γ secretion showed no significant differences between two groups（ P〈0. 05）. The GEA group had lower expression of PD-L1 in PBMCs,and higher expression of CD8^＋T cell apoptosis rate than GA group（ P〈0. 05）,but the level of IFN-γ secretion by CD 8＋T cells was higher than that in GA group（ P〈0. 0 5）. Conclusion The thoracic epidural block may partially reverse the up-regulation of PD-L1 in monocytes by reducing perioperative stress response,thereby to alleviate inhibitory function of IFN-γ secretion and proliferation of T cells and improve immune function of elderly patients with esophageal cancer.