论文部分内容阅读
目的:观察耐甲氧西林金黄色葡萄球菌（MRSA）脓毒症患者外周血自然杀伤（NK）细胞亚群和功能，探讨基质金属蛋白酶（MMP）对MRSA脓毒症患者NK细胞功能的影响。方法:选择2017年1月至2018年6月本科收治的MRSA脓毒症患者21例和健康对照者（NC）11例，分离外周血单个核细胞（PBMC），流式细胞术检测NK细胞亚群比例。通过检测PBMC与靶细胞共培养体系中CD107a、CD69、CD16的表达评估NK细胞功能。分选NK细胞，实时定量PCR法检测MMP mRNA，使用MMP抑制剂刺激NK细胞，检测共培养体系中CD107a变化。组间比较采用成组n t检验或配对n t检验。n 结果:总NK细胞比例在NC和MRSA脓毒症患者之间的差异无统计学意义（n P>0.05），MRSA脓毒症患者CD56brightCD16-NK细胞[（5.36±1.02)% n vs (4.30±0.89)%]和CD56-CD16+NK细胞[（24.04±2.92）% n vs （9.70±1.54）%]升高（n P<0.05），CD56dimCD16+NK细胞（71.22±13.03）% n vs （87.64±7.05%）]降低（n P<0.01）。NK细胞通过不同受体介导相应靶细胞杀伤后，MRSA脓毒症患者NK细胞中CD107a[（33.55±3.84）% n vs （25.34±6.20%）]和CD69[（14.96±1.47%） n vs （18.80±1.49）%]比例低于NC（n P<0.01），CD16 MFI[（247.1±50.31） n vs （189.4±57.54）]高于NC（n P<0.01）。MMP-1/2/3/9 mRNA在MRSA脓毒症患者NK细胞中的相对表达量升高（n P0.05). CD56brightCD16n -NK [(5.36±1.02)% n vs (4.30±0.89)%] and CD56n -CD16n +NK [(24.04±2.92)% n vs (9.70±1.54)%] percentage was elevated (n P<0.05), while CD56dimCD16n +NK percentage [(71.22±13.03)% n vs (87.64±7.05)%, n P<0.01] was reduced in MRSA sepsis. NK cells recognized and killed target cells via different receptors upon activation. CD107a [(33.55±3.84)% n vs (25.34±6.20)%] and CD69 percentage [(14.96±1.47)% n vs(18.80±1.49)%] was decreased (n P<0.0001), while CD16 MFI was increased [(247.1±50.31) n vs (189.4±57.54), n P<0.01] in MRSA sepsis patients in comparison with healthy controls. MMP-1/2/3/9 mRNA relative levels were elevated in purified NK cells from MRSA sepsis patients (n P<0.01). Inhibition of MMP in NK cells from MRSA sepsis patients promoted CD107a percentage [(33.67±8.03)% n vs (25.87±6.23)%, n P=0.018].n Conclusions:NK cell subsets imbalance and exhaustion is existed in MRSA sepsis, which might be due to the MMP-induced down-regulation of antibody-dependent cell-mediated cytotoxicity.