体外循环下心脏瓣膜置换术患者术后谵妄与外周血单个核细胞焦亡的关系

Relationship between postoperative delirium and pyroptosis of peripheral blood mononuclear cells in patients undergoing heart valve replacement with cardiopulmonary bypass

目的评价体外循环(CPB)下心脏瓣膜置换术患者术后谵妄(POD)与外周血单个核细胞(PBMCs)焦亡的关系。方法择期行CPB下心脏瓣膜置换术患者60例,性别不限,年龄45~64岁,BMI 18~25 kg/m^(2),ASA分级Ⅱ或Ⅲ级,NYHA心功能分级Ⅱ或Ⅲ级。术后3 d内采用ICU意识障碍评估法(CAM-ICU)进行POD的评估,按照是否发生POD分为2组:POD组(n=45)和无POD组(NPOD组,n=15)。于麻醉诱导后切皮前(T_(1))、CPB开始后30 min(T_(2))、CPB停止即刻(T_(3))和停止后24 h(T_(4))时采集颈内静脉血样,采用ELISA法测定血浆S100β和神经元特异性烯醇化酶(NSE)的浓度,测定血浆IL-18和IL-1β的浓度。采用Western blot法检测PBMCs核苷酸结合寡聚化结构域样受体蛋白3(NLRP3)、caspase-1及消皮素-D(GSDMD)的表达。记录术后机械通气时间及ICU停留时间。结果与NPOD组比较,POD组T2~4时血浆S100β、NSE、IL-18、IL-1β浓度、PBMCs NLRP3、caspase-1和GSDMD表达水平升高,术后机械通气时间和ICU停留时间均延长(P<0.05)。与T1时比较,2组患者T2~4时血浆S100β、NSE、IL-18、IL-1β浓度、PBMCs NLRP3、caspase-1和GSDMD表达水平升高(P<0.05)。结论CPB下心脏瓣膜置换术患者POD的发生可能与PBMCs焦亡有关。

Objective To evaluate the relationship between postoperative delirium(POD)and pyroptosis of peripheral blood mononuclear cells(PBMCs)in the patients undergoing heart valve replacement with cardiopulmonary bypass(CPB).Methods Sixty patients of either sex,aged 45-64 yr,with body mass index of 18-25 kg/m^(2),of American Society of Anesthesiologists physical statusⅡorⅢ,with New York Heart Association classⅡorⅢ,undergoing elective heart valve replacement with CPB,were enrolled in this study.POD was assessed by the Consciousness Assessment Method for the intensive care unit(CAM-ICU)within 3 days after operation.All the patients were divided into 2 groups according to whether POD occurred within 3 days after operation:POD group(n=45)and non-POD group(NPOD group,n=15).After induction of anesthesia and before skin incision(T_(1)),at 30 min after start of CPB(T_(2)),immediately after termination of CPB(T_(3))and at 24 h after termination of CPB(T_(4)),blood samples from the internal jugular vein were collected to determine the concentrations of plasma S100β,neuron-specific enolase(NSE),interleukin(IL)-18 and IL-1β(by enzyme-linked immunosorbent assay)and expression of nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3),caspase-1 and gasdermin D(GSDMD)in PBMCs(by Western blot).The postoperative mechanical ventilation time and length of stay in ICU were recorded.Results Compared with NPOD group,the concentrations of plasma S100β,NSE,IL-18 and IL-1βwere significantly increased,the expression of NLRP3,caspase-1 and GSDMD in PBMCs was up-regulated at T2-4,and the postoperative mechanical ventilation time and length of stay in ICU were prolonged in POD group(P<0.05).Compared with those at T1,the concentrations of plasma S100β,NSE,IL-18 and IL-1βwere significantly increased,and the expression of NLRP3,caspase-1 and GSDMD in PBMCs was up-regulated at T2-4 in POD and NPOD groups(P<0.05).Conclusion The occurrence of POD may be associated with the pyroptosis of PBMCs in patients undergoing heart valve replacement with CPB.