2026 年第 5 期 第 21 卷

中性粒细胞弹性蛋白酶抑制剂对高海拔地区脓毒症相关急性呼吸窘迫综合征疗效的临床观察研究

Clinical observational study on the efficacy of neutrophil elastase inhibitor in the treatment of sepsis-associated acute respiratory distress syndrome at high altitude areas

作者：刘晓琴1马启霞1郭利涛2史生辉1孙斌1许雪侠1

英文作者：Liu Xiaoqin1 Ma Qixia1 Guo Litao2 Shi Shenghui1 Sun Bin1 Xu Xuexia1

单位：1青海省人民医院重症医学科，西宁810007；2西安交通大学第一附属医院重症医学科，西安710061

英文单位：1Department of Critical Care Medicine Qinghai Provincial People′s Hospital Xining 810007 China； 2Department of Critical Care Medicine the First Affiliated Hospital of Xi′an Jiaotong University Xi′an 710061 China

关键词：脓毒症；急性呼吸窘迫综合征；西维来司他钠；中性粒细胞弹性蛋白酶；中性粒细胞弹性蛋白酶抑制剂

英文关键词：Sepsis;Acuterespiratorydistresssyndrome;Sivelestatsodium;Neutrophilelastase;Neutrophilelastaseinhibitor

• 摘要：

• 目的 评估中性粒细胞弹性蛋白酶（NE）抑制剂西维来司他钠对高海拔地区脓毒症相关急性呼吸窘迫综合征（ARDS）患者的治疗效果。方法 选取青海省人民医院重症医学科2023年8月至2024年8月收治的高海拔地区脓毒症相关ARDS患者56例，采用随机数字表法将患者分为观察组（27例）和对照组（29例）。2组按需给予ARDS标准治疗，观察组在标准治疗的基础上联合西维来司他钠治疗。比较2组入院第1、7天急性生理学与慢性健康系统评分系统Ⅱ（APACHEⅡ）评分、序贯器官衰竭评估（SOFA）评分、氧合指数、降钙素原、白细胞介素6（IL-6）、白细胞计数、高敏C反应蛋白（hs-CRP）水平，采用酶联免疫吸附试验法检测NE水平。结果 2组入院第1天APACHEⅡ、SOFA评分比较差异均无统计学意义（均P＞0.05）。入院第7天，2组APACHEⅡ、SOFA评分均低于第1天，且观察组SOFA评分低于对照组（均P＜0.05）。观察组与对照组入院第1天氧合指数比较差异无统计学意义［130（107,174）比159（113,190）］（Z＝-1.369，P＝0.171）。入院第7天2组氧合指数均高于第1天（均P＜0.001），且观察组高于对照组［286（240，316）比230（197,264）］（Z=-3.281，P<0.001）。入院第1天，2组白细胞计数、降钙素原、IL-6、hs-CRP水平比较差异均无统计学意义（均P＞0.05）。第7天，2组白细胞计数、降钙素原、IL-6、hs-CRP水平均低于治疗前，且观察组均低于对照组（均P＜0.05）。入院第1天，观察组与对照组NE水平比较差异无统计学意义［（56±4）μg/L比（56±5）μg/L］（t＝-0.364，P＝0.717）。入院第7天，2组NE水平均低于第1天（均P＜0.05），且观察组低于对照组［（48±4）μg/L比（54±5）μg/L］（t=4.620，P＜0.001）。结论 西维来司他钠可显著改善高海拔地区脓毒症相关ARDS患者的氧合指数，减轻器官损伤，抑制过度炎症反应。

• Objective To evaluate the therapeutic effect of sivelestat sodium, a neutrophil elastase (NE) inhibitor, on sepsis-associated acute respiratory distress syndrome (ARDS) at high altitude areas. Methods A total of 56 patients with sepsis-associated ARDS at high altitudes admitted to the Department of Critical Care Medicine, Qinghai Provincial People′s Hospital from August 2023 to August 2024 were enrolled and randomly divided into observation group (27 cases) and control group (29 cases) by random number table method. Both groups received standard ARDS treatment as needed, and the observation group was additionally treated with sivelestat sodium on the basis of standard treatment. Acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score, sequential organ failure assessment (SOFA) score, oxygenation index, procalcitonin, interleukin-6 (IL-6), white blood cell count, high-sensitivity C-reactive protein (hs-CRP) levels on day 1 and day 7 after admission were compared between the two groups. NE level was detected by enzyme-linked immunosorbent assay. Results There were no significant differences in APACHE Ⅱ and SOFA scores between the two groups on day 1 (both P>0.05). On day 7, APACHE Ⅱ and SOFA scores in both groups were lower than those on day 1, and SOFA score in the observation group was lower than that in the control group (all P<0.05). There was no significant difference in oxygenation index between the observation group and the control group on day 1 ［130(107, 174) vs 159(113, 190)］(Z=-1.369, P=0.171). On day 7, oxygenation index in both groups were higher than those on day 1 (both P<0.001), and that in the observation group was higher than that in the control group ［286(240, 316) vs 230(197, 264)］(Z=-3.281, P<0.001). On day 1, there were no significant differences in white blood cell count, procalcitonin, IL-6 and hs-CRP levels between the two groups (all P>0.05). On day 7, the above indicators in both groups were lower than those before treatment, and those in the observation group were lower than those in the control group (all P<0.05). On day 1, there was no significant difference in NE level between the observation group and the control group ［(56±4)μg/L vs (56±5)μg/L］(t=-0.364, P=0.717). On day 7, NE levels in both groups were lower than those on day 1 (both P<0.05), and that in the observation group was lower than that in the control group ［(48±4)μg/L vs (54±5)μg/L］(t=4.620, P<0.001). Conclusion Sivelestat sodium can significantly improve oxygenation index, alleviate organ injury and inhibit excessive inflammatory response in patients with sepsis-associated ARDS at high altitudes.