火器伤烟雾吸入致吸入性肺损伤细胞因子的变化及与多器官功能损害的关系

Study on changes in inflammatory cytokines and the relationship to multiple organ injury in rats with aspiration lung injury after fire - arm injury

目的 观察火器伤烟雾吸入致重度吸入性肺损伤后支气管肺泡灌洗液(BALF)中致炎、抗炎细 胞因子含量变化,及其在多器官功能损害中的作用。方法 复制火器伤致大鼠重度吸入性肺损伤模型。观察 大鼠伤后2、4、6、8、12和24 h肺湿重／于重比,BALF中自蛋白、乳酸脱氢酶(LDH)、肿瘤坏死因子-α (TNF-α)、白细胞介素-6(IL-6)、IL-4的含量,外周血丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、血尿 素氮(BUN)、血肌酐(SCr)、肌酸激酶同工酶(CK-MB)含量,并与正常对照组比较。结果 大鼠肺湿重／干重 比、BALF中白蛋白及LDH含量随时间的延长而增加;TNF-α在损伤后即增加,2 h达高峰;IL-6损伤后 4 h明显增加,且伤后4-24 h保持较高浓度;IL-4于伤后6-8 h下降。外周血ALT、AST、BUN、SCr、 CK-MB伤后持续增加。结论 细胞因子可能是介导多器官功能损害的直接介质。多器官功能损害可能由 TNF-α触发,随后引起细胞因子的级联反应,致炎因子IL-6的持续高表达和抑炎因子IL-4后期失控加剧 了MOF的发展。

Objective To observe the phasic variations in concentrations of pro-inflammatory and anti-inflammatory cytokines, and to explore their potential roles in the occurrence and development process of multiple organ dysfunction. Methods Fire-arm induced aspiration lung injury model was replicated. The following parameters were observed： wet/dry weight ratio of rat＇s lungs, contents of albumin and lactate dehydrogenase （LDH）, concentrations of tumor necrosis factor-α （TNF-α）, interleukin-6 （IL-6） and IL-4 in bronchoal alveolar lavage fluid （BALF）, contents of alanine amino transferase （ALT）, asparate aminotransferase （AST）, blood urea nitrogen （BUN）, serum creatinine （SCr）, and MB isoenzyme of creatine kinase （CK-MB）. Results The wet/dry weight ratio of rat＇s lungs and contents of albumin and LDH in BALF increased with the passage of time. The concentration of TNF-α increased immediately after injury and reached the peak value at 2 hours. The concentration of IL-6 increased obviously 4 hours after injury, and maintained a high level from 4 hours to 24 hours. The concentration of IL-4 decreased from 6 hours to 8 hours after injury. The contents of ALT, AST, BUN, SCr and CK-MB increased continually after injury. Conclusion Cytokines are the direct mediators for multiple organ failure （MOF）, and MOF is triggered by TNF-α and a cascade of cytokine release, with a prolonged high -expression of IL-6. The loss of control of IL-4 aggravates the development of MOF.