【作者】 杨丽娟；

【导师】 王莉；

【作者基本信息】 河北医科大学 ， 麻醉学（专业学位）， 2021， 硕士

【摘要】 目的:探讨右美托咪定（Dex）对体外循环（CPB）心脏瓣膜置换术患者炎症反应和外周血单核细胞焦亡的的影响及机制。方法:选取于本院择期行体外循环心脏瓣膜置换术患者44例,性别不限,年龄45～64岁,BMI 18～25 kg/m²,ASA分级Ⅱ或Ⅲ级,NYH A心功能分级Ⅱ或Ⅲ级,根据随机数字表法,将其分为2组（n=22）:右美托咪定组（Dex组）和生理盐水组（NS组）。Dex组于常规麻醉诱导后经静脉输注Dex0.5μg/kg,10 min内输注完毕,继之以0.5μg·kg^-1·h^-1的速率输注至术毕;NS组以等容量生理盐水替代。于麻醉诱导后切皮前（T1）、CPB开始后30 min（T2）、CPB停止即刻（T3）及停止后24 h（T4）时采集患者颈内静脉血样,采用ELISA法测定血浆IL-18、IL-1β的浓度,采用Fi coll密度梯度分离法提取单个核细胞,诱导贴壁后得到单核-巨噬细胞,采用Western blot法检测单核细胞中NLRP3、Caspase-1及GSDMD的表达。记录术中丙泊酚用量、舒芬太尼用量、去甲肾上腺素用量、术后机械通气时间及ICU停留时间。结果:两组患者外周血的血浆IL-18、IL-1β水平与T1时刻比较,在T2-4时刻升高,差异有统计学意义（P<0.05）。与NS组比较,Dex组血浆IL-18、IL-1β水平在T2-4时刻均降低,差异有统计学意义（P<0.05）。两组患者外周血单核细胞中NLRP3、Caspase-1、GSDMD蛋白表达,与T1时刻比较,在T2-4时刻升高,差异有统计学意义（P<0.05）。与NS组比较,Dex组NLRP3、Caspase-1、GSDMD蛋白表达在T2-4时刻均降低,差异有统计学意义（P<0.05）。两组患者术后机械通气时间比较,Dex组较NS组降低,差异有统计学意义（P<0.05）。结论:Dex减轻了体外循环心脏瓣膜置换术患者的炎症反应,其抗炎机制可能与抑制NLRP3、Caspase-1蛋白表达,降低其下游炎症因子IL-18、IL-1β水平,抑制细胞焦亡有关。更多还原

【Abstract】 Objective:The study was aimed to determine the effects and mechanism of dexmedetomidine（Dex）on inflammatory response and peripheral blood monocytes pyroptosis in patients with cardiac valve replacement under cardiopulmonary bypass.Methods:44 American Society of Anesthesiologists physical statusⅡorⅢpatients of both sexesp of New York Heart AssociationⅡorⅢp aged45-64 yrp BMI 18-25 kg/m²p receiving elective cardiac valve replacement with cardiopulmonary bypassp were randomly divided into 2 groups（n=22）according to the random number table method:dexmedetomidine group（Group Dex）and normal saline group（Group NS）.Patients in Group Dex received an infusion of 0.5μg/kg（initial dose）within 10 min after anesthesia induced intubationp followed by continuous infusion at 0.5μg·kg^-1·h^-1until the end of the operationp while patients in Group NS were injected with the equal volume of normal saline.The blood samples of internal jugular vein were collected before skin incision（T1）p 30 min after the initiation of CPB（T2）p immediately after the end of CPB（T3）and 24 h after CPB（T4）.The concentrations of plasma IL-18 and IL-1βwere determined by ELISAp mononuclear cells were extracted by Ficoll density gradient separationp and NLRP3p Caspase-1 and GSDMD protein expression in monocytes was detected by Western blot.Propofolp sufentanil and norepinephrine consumption during operationp the time of postoperative mechanical ventilation and the stay time of ICU were recorded.Results:The levels of plasma IL-18 and IL-1βin the two groups at T2-4were significantly higher than those at T1（P<0.05）.Compared to Group NSp the levels of plasma IL-18 and IL-1βin Group Dex decreased at T2-4（P<0.05）.Compared with T1p the protein expression of NLRP3p Caspase-1and GSDMD in peripheral blood monocytes of the two groups increased at T2-4（P<0.05）.Compared to Group NSp NLRP3p Caspase-1 and GSDMD protein expression in Group Dex decreased at T2-4（P<0.05）.Compared with Group NSp the time of postoperative mechanical ventilation in Group Dex decreased（P<0.05）.Conclusion:Dex alleviates the inflammatory response in patients undergoing cardiac valve replacement with cardiopulmonary bypassp the anti-inflammatory mechanism may be related to the inhibition of the expression of NLRP3 and Caspase-1 proteins and the decrease of the levels of downstream inflammatory cytokines IL-18 and IL-1βp thus inhibiting pyroptosis.更多还原