Objective To investigate the effect ofulinastatin on severe heat-stroke with acute lung injury induced by severe heat stroke.Methods Thirty severe heat stroke patients were divided into conventional group (n=15) and ulinastatin group (n=15) randomly,with another 80 healthy adults serving as controls.The baseline data such as age,gender,onset period and APACHE Ⅱ scores were recorded and compared between the two groups on admission.Peripheral leucocyte counts,oxygenation index and Murray scores were determined on the 1st,3rd and 5th day.The concentration of inflammatory mediators in bronchoalveolar lavage fluid (BALF) and alveolar macrophage supernatant were detected by enzyme-linked immunosorbent assay (ELISA).Western blotting and real-time PCR were used to measure expression of triggering receptor-1 on myeloid cells (TREM-1) on alveolar macrophages.Furthermore,comparison was made in terms of the ventilation period,ICU stay time and mortality in 28 days between the two groups.Results No differences were found in age,gender,onset period and APACHE Ⅱ scores between the two groups (P＞0.05).Compared with the conventional group,peripheral leucocyte counts and Murray scores in the ulinastatin group significantly decreased on the 3rd and 5th day (P＜0.05,P＜0.01).But oxygenation index was higher in the ulinastatin group than in the conventional group (P＜0.05).The concentration of TNF-α and IL-6 in BALF was lower in the ulinastatin group than in the conventional group (on the 3rd day:P＜0.05,P＜0.01;on the 5th day:P＜0.01,P＜0.01).The concentration of TNF-α and IL-6 in alveolar macrophage supernatant was lower in the ulinastatin group than in the conventional group (on the 3rd day:-P＜0.05,P＜0.01;on the 5th day:P＜0.01,P＜0.05).The expression of TREM-1 protein on alveolar macrophages were lower in the ulinastatin group than in the conventional group (on the 3rd day P＜0.01;on the 5rd day P＜0.05).TREM-1 mRNA was lower in the ulinastatin group than in the conventional group (on the 3rd day:P＜0.05;on the 5th day:P＜0.05).Eventually,the treatment of ulinastatin shorten ventilation period and ICU stay time (P＜0.01,P＜0.05).Nonetheless,it failed to show any improvement in terms of the mortality during 28 days (P＞0.05).Conclusion Our study exhibited that ulinastatin had good effect on the heat stroke patients with acute lung injury and it helped reduce the inflammatory reaction of pulmonary tissues.The underlying mechanism of these effects might lie in its ability to reduce heat stroke-induced inflammatory secretion and expression of TREM-1 on alveolar macrophage.%目的 观察乌司他丁对重症中暑急性肺损伤的临床疗效.方法 30例重症中暑患者按随机数字表法分为常规治疗组和乌司他丁组,每组15例,另设健康对照组(n=8).比较两组中暑患者人院时的年龄、性别、发病至接受治疗的时间以及APACHEⅡ评分等基线情况的差异,以及人院后第0、3、5天外周血白细胞计数,Murray评分和氧合指数的差别,并通过酶联免疫吸附法(ELISA)测定支气管肺泡灌洗液(BALF)与肺泡巨噬细胞培养上清炎症介质的浓度,采用免疫印迹法和实时定量PCR法检测肺泡巨噬细胞髓样细胞触发受体-1(TREM-1)表达情况.观察并比较两组患者的机械通气时间、ICU住院时间和28d病死率.结果 两组患者人院时的年龄、性别、发病至接受治疗的时间以及APACHEⅡ评分差异无统计学意义(P＞0.05).治疗后第3、5天,乌司他丁组外周血白细胞计数、Murray评分均低于常规治疗组(P＜0.05或P＜0.01),而氧合指数高于常规治疗组(P＜0.05);BALF及肺泡巨噬细胞培养上清中的TNF-α和IL-6浓度均低于常规治疗组(P＜0.05或P＜0.01),肺泡巨噬细胞TREM-1 mRNA和蛋白表达水平明显低于常规治疗组(P＜0.01或P＜0.05).乌司他丁组重症中暑患者的机械通气时间和ICU住院时间明显低于常规治疗组(P＜0.01或P＜0.05),但28d病死率两组比较差异无统计学意义(P＞0.05).结论 乌司他丁对重症中暑急性肺损伤具有良好的临床疗效,有利于减轻肺组织炎症反应程度,其机制可能与乌司他丁调控重症中暑肺泡巨噬细胞的炎症分泌活性及TREM-1表达有关.
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