【作者】 梁志欣；

【导师】 陈良安； 张波；

【作者基本信息】 中国人民解放军军医进修学院 ， 内科学， 2012， 博士

【摘要】 目的：ALI/ARDS是临床常见危重症，目前缺乏有效的治疗方法。动物实验及体外研究表明全氟化碳汽化吸入对ALI/ARDS具有治疗作用。本研究通过随机对照临床试验评价全氟化碳汽化吸入对ALI/ARDS的临床疗效和安全性并对其生物学机制进行初步研究。方法：（1）应用无创正压通气的ALI/ARDS患者随机分入治疗组和对照组，治疗组连续汽化吸入全氟化碳3天，200ml/次，1次/12小时，对照组汽化吸入注射用水，观察治疗后两组患者氧合指数、气管插管率、28天ICU病死率及并发症差异；（2）应用有创正压通气的ALI/ARDS患者随机分入治疗组和对照组，治疗组连续汽化吸入全氟化碳5天，100ml/次，1次/8小时，对照组汽化吸入注射用水，观察治疗后两组患者氧合指数、28天ICU病死率、28天内无机械通气时间及并发症差异；（3）检测全氟化碳汽化吸入前后ALI/ARDS患者血标本白细胞计数、TNF-a和IL-1β水平变化并应用microRNA芯片和基因表达谱芯片高通量研究全氟化碳吸入前后差异表达的microRNA和基因。结果：（1）应用无创正压通气ALI/ARDS患者19例入选治疗组，20例入选对照组。与对照组比较，治疗组患者氧合指数(P>0.05)、气管插管需求率（P=0.73）、28天ICU病死率(P=0.71)未见统计学差异，未发现与PFC汽化吸入相关的并发症；（2）应用有创正压通气ALI/ARDS患者12例入选治疗组，10例入选对照组。与对照组比较，治疗组患者氧合指数(P>0.05)、28天内无机械通气时间（P=0.39）、28天ICU病死率(P=0.67)未见统计学差异，治疗组第3天平均动脉压升高（99.57vs.82.44,P=0.02）；（3）全氟化碳汽化吸入后C反应蛋白出现下降趋势，但与对照组比较未达到统计学差异（P>0.05），对白细胞计数、TNF-a、IL-1β水平无影响。全氟化碳汽化吸入导致miR-30C-1-3p、 miR-3178、 miR-4534、hsa-miR-4725-3p、miR-92b-5p共5个miRNA和255条基因表达出现变化。结论：（1）应用无创正压通气汽化吸入全氟化碳治疗ALI/ARDS临床患者与常规无创正压通气治疗比较疗效无差异且安全；（2）应用有创正压通气汽化吸入全氟化碳治疗ALI/ARDS临床患者与常规有创正压通气治疗比较疗效无差异但可能造成血流动力学改变；（3）全氟化碳汽化吸入可能通过影响多个miRNA和基因的表达发挥生物学作用。更多还原

【Abstract】 Objective：Acute lung injury (ALI)/Acute Respiratory Distress Syndrome (ARDS)is a serious and common condition for which there are currently no specific strategiesfor treatment. It has been proved that perfluorocarbon vaporization inhalation hastherapeutic effects on ALI/ARDS in animal models and vitro studies. The study aimedto evaluate the clinical effects, mechanism and safety of perfluorocarbon vaporizationinhalation through randomized controlled trial.Methods:（1）The ALI/ARDS patients who received noninvasive positive pressureventilation (NPPV) were randomly divided into treatment or control group. Patients intreatment group received200ml perfluorocarbon vaporization inhalation every12hoursfor3days successively, patients in control group received sterile water inhalation. Aftertreatment, a comparison was made in oxygenation index, the proportion of patientsrequiring intubation, mortality in ICU within28days and the incidence ofcomplications between the two groups;（2）The ALI/ARDS patients who receivedinvasive positive pressure ventilation (IPPV) were randomly divided into treatment orcontrol group. Patients in treatment group received100ml perfluorocarbon vaporizationinhalation every8hours for5days successively, patients in control group receivedsterile water inhalation. After treatment, a comparison was made in oxygenation index,mortality in ICU within28days, the numbers of ventilator-free days between day1andday28, the incidence of complications between the two groups;（3）The level of whiteblood cell count, TNF-a and IL-1βwere detected before and after the therapy.ThemicroRNAs and genes differently expressed before and after the inhalation of theperfluorocarbon were detected by the application of microRNA and cDNA microarrays.Results（:1）19patients who received NPPV were divided into treatment group and20patients were divided into control group. There was no significant difference inoxygenation index(P>0.05), the proportion of patients requiring intubation（P=0.73）,mortality in ICU within28days (P=0.71) and the incidence of complications betweenthe two groups; （2）12patients who received IPPV were divided into treatment group and10patients were divided into control group. There was no significant difference inoxygenation index(P>0.05), the numbers of ventilator-free days between day1and day28（P=0.39），mortality in ICU within28days (P=0.67) between the two groups. But onthe third days, the mean arterial blood pressure in treatment group was higher than thatin the control group（99.57vs.82.44, P=0.02）;（3）The level of C-reactive protein of treatment group declined but was notsignificantly different from that of the control group (P>0.05). There was nosignificant difference in the level of white blood cell count, TNF-a and IL-1βbetweenthe two groups. Different expressions were detected in5miRNAs (miR-30C-1-3p,miR-3178, miR-4534, hsa-miR-4725-3p, miR-92b-5p) and255genes before and afterthe inhalation of the perfluorocarbon.Conclusions:（1）The efficacy of perfluorocarbon vaporization inhalation throughNPPV is not different from NPPV and is safe for ALI/ARDS patients;（2）The efficacyof perfluorocarbon vaporization inhalation through IPPV is not different from IPPV forALI/ARDS patients, but it may result in hemodynamic changes;（3）Perfluorocarbonvaporization inhalation may play a biological role by affecting the expression in anumber of miRNAs and genes.更多还原