【摘要】 目的 探讨乌司他丁（UTI）对行体外循环（CPB）下心脏瓣膜置换术患者围术期炎性反应和外周血单个核细胞（PBMCs）焦亡的影响及其机制。方法 选择行CPB下心脏瓣膜置换术患者60例，采用随机数字表法分为2组：乌司他丁组（UTI组）和生理盐水组（NS组）,每组30例。UTI组患者接受总剂量为20 000 U/kg的UTI,半量于手术切皮前输注完毕，另半剂量经CPB管路给药。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）时采集颈内静脉血样，采用酶联免疫吸附法（ELISA）测定血浆白细胞介素（IL）-18、IL-1β的浓度，采用Western blot法检测单核细胞中核苷酸结合寡聚化结构域样受体蛋白3 （NLRP3）、半胱氨酰天冬氨酸特异性蛋白酶1 （Caspase-1）及消皮素-D （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重症监护室（ICU）停留时间。结果 与T₁时相比，两组患者T₂～T₄时血浆IL-18、IL-1β和单核细胞NLRP3、Caspase-1、GSDMD蛋白表达均显著升高（P<0.05）。与NS组相比，UTI组T₂～T₄时血浆IL-18、IL-1β浓度和PBMCs中NLRP3、Caspase-1、GSDMD蛋白表达均显著降低（P<0.05）。两组患者术中丙泊酚用量、舒芬太尼用量、去甲肾上腺素用量及ICU停留时间差异均无统计学意义（P>0.05）;UTI组术后机械通气时间较NS组显著降低，差异有统计学意义（P<0.05）。结论 UTI减轻了CPB下心脏瓣膜置换术患者围术期炎性反应，其抗炎机制可能与抑制PBMCs中NLRP3、Caspase-1蛋白表达、降低其下游炎症因子IL-18、IL-1β水平、抑制PBMCs焦亡有关。更多还原

【Abstract】 Objective To investigate the effect of ulinastatin（UTI） on perioperative inflammation and pyrolysis of peripheral blood mononuclear cells（PBMCs） and its mechanism in patients undergoing heart valve replacement under cardiopulmonary bypass（CPB）.Methods A total of 60 patients undergoing heart valve replacement under CPB were divided into 2 groups by a random number table: ulinastatin group（UTI group） and normal saline group（NS group）,with 30 cases in each group.Patients in the UTI group received a total dose of 20,000 U/kg of UTI,half of which was infused before surgical skin incision, and the other half of the dose was administered via the CPB line.The drug intervention of NS group was replaced with equal volume of normal saline.Blood samples from the internal jugular vein were collected before skin incision（T₁）,30 min after starting CPB（T₂）,immediately after stopping CPB（T₃） and 24 h after cessation（T₄） after induction of anesthesia, and enzyme-linked immunosorbent assay（ELISA） was used to detect the concentration of interleukin（IL）-18 and IL-1β in plasma.The expressions of nucleotide-binding oligomerization domain-like receptor protein 3（NLRP3） and cysteinyl aspartate specific protease 1（Caspase-1） in monocytes and Gasdermin-D（GSDMD） were detected by Western blot.The intraoperative dosage of propofol, sufentanil and norepinephrine, postoperative mechanical ventilation time and intensive care unit（ICU） stay time were recorded.Results Compared with T₁,the plasma IL-18,IL-1β and monocyte NLRP3,Caspase-1,GSDMD protein expressions were significantly increased at T₂～T₄ in the two groups of patients（P<0.05）.Compared with the NS group, the concentrations of plasma IL-18 and IL-1β and the expression of NLRP3,Caspase-1 and GSDMD protein in PBMCs were significantly reduced at T₂～T₄ in the UTI group（P<0.05）.There was no significant difference in the intraoperative propofol dosage, sufentanil dosage, norepinephrine dosage, or ICU stay time between the two groups of patients（P>0.05）;the postoperative mechanical ventilation time of the UTI group was significantly lower than that of the NS group, and the difference was statistically significant（P<0.05）.Conclusion UTI reduces the perioperative inflammatory response in patients undergoing heart valve replacement under CPB,and its anti-inflammatory mechanism may be related to inhibiting the expression of NLRP3 and Caspase-1 protein in PBMCs, reducing the levels of downstream inflammatory factors IL-18 and IL-1β,and inhibiting pyroptosis of PBMCs.更多还原