利多卡因对宫颈癌根治术患者应激激素及NK细胞杀伤力的影响

摘要

Objective To discuss the effects of lidocaine infusion on perioperative immune function by evaluating the levels of stress hormone and natural killer (NK) cell cytotoxicity.Methods Thirty-five patients of American Society of Anesthesiologists physical status Ⅰ or Ⅱ,aged 35-65 yr,undergoing elective radical hysterectomy,were randomized into lidocaine group (group L)and control group (group C).Fifteen minutes before anesthesia induction,a bolus of 1.5 mg/kg of lidocaine was administered iv.to each patient in group L and followed by a continuous infusion at 1.5 mg·kg-1 ·h-1 lasting to the end of surgery.Meanwhile,the patients in group C received the same volume of saline.Venous blood samples were collected individually 24 h before the operation,the end of the operation and 48 h after the operation.Levels of prostaglandin,epinephrine and norepinephrine were assayed by ELISA kits.NK Cells were obtained by CD56 antibody magnetic isolation.The cytotoxicity of NK cell was detected by LDH releasing assay,and phosphor-protein kinase A (p-PKA)and protein kinase A (PKA) were detected by Western blotting.Results There were no significantly different in the plasm levels of PGF2,EP1 and NE.The plasm levels of prostaglandin (562.5±98.2 vs.663.2±119.0) pg/ml,epinephrine (24.9±4.8 vs.29.7±3.5) pg/ml and norepinephrine (408.3 ±47.2 vs.499.6±45.6) pg/ml in patients of group L were lower than those in group C (P＜0.05)48 h after the surgery.The cytotoxicity of NK cell was higher in group L than that in group C (44.1 ±5.0 vs.37.1±5.5)％ (P＜0.05) 48 h after the surgery.The ratio of p-PKA/PKA was lower in group L than that in guoup C (0.060±0.008 vs.0.099±0.011) (P＜0.05) at the end of the surgery.Conclusion Perioperative intravenous lidocaine infusion can reduce the level of plasma catecholamine and PGE2,and protect the cytotoxicity of NK cell,possibly via inhibiting of cAMP-PKA signaling pathway.%目的 观察围术期静脉输注利多卡因对宫颈癌根治术患者应激激素和自然杀伤(NK)细胞杀伤力的影响,探讨利多卡因围术期免疫保护作用.方法 择期拟行宫颈癌根治术患者35例,年龄35～65岁,ASA Ⅰ或Ⅱ级,采用随机数字表法分为利多卡因组(L组)和对照组(C组).麻醉诱导前15 min,L组患者静注利多卡因1.5 mg/kg,随后利多卡因1.5 mg·kg-1 ·h-1持续泵注至患者出室;C组患者给予等量生理盐水.分别于术前24 h、术毕即刻、术后48 h采集患者外周静脉血,ELISA法测定血浆PGE2、EPI、NE浓度.免疫磁珠法分离NK细胞,乳酸脱氢酶释放法检测NK细胞杀伤力,Western blot法检测NK细胞磷酸化蛋白激酶A(p-PKA)和蛋白激酶A(PKA)表达.结果 术前24 h两组患者血浆PGE2、EP1和NE浓度差异无统计学意义.术后48 h,L组血浆PGE2浓度[(562.5±98.2)pg/ml vs (663.2±119.0) pg/ml]、EPI浓度[(24.9±4.8)pg/ml vs(29.7±3.5)pg/ml]、NE浓度[(408.3±47.2)pg/ml vs (499.6±45.6)pg/ml]明显低于C组(P＜0.05).术后48 h,L组NK细胞杀伤力明显高于C组[(44.1±5.0)％ vs(37.1±5.5)％,P＜0.05].术毕即刻,L组p-PKA/PKA明显低于C组(0.060±0.008 vs 0.099±0.011)(P＜0.05).结论 围术期静脉输注利多卡因能降低宫颈癌根治术患者血浆PGE2及儿茶酚胺水平;保护NK细胞对肿瘤细胞的杀伤能力,其机制可能是通过抑制cAMP-PKA信号通路.