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目的 通过糖皮质激素对大鼠烟雾吸人性肺损伤进行干预,探索其对凝血功能的影响.方法 以雄性SD大鼠为研究对象,将150只大鼠随机(随机数字法)分为对照组(吸入空气)、烟雾吸人组(s组,烟雾吸人30 min)、烟雾+高剂量甲泼尼龙(methyl prednislolone,MP)组(s+HMP组,腹腔注射MP 40 mg/kg)、烟雾+中剂量MP组(s+MMP组,腹腔注射MP 4 mg/kg)、烟雾+低剂量MP组(s+LMP组,腹腔注射MP 0.4 mg/kg)(均n=30),烟雾干预后24 h,计算生存曲线,收集肺组织进行病理检测及干湿比测定,收集动脉血进行血气测定,对肺内及血浆中凝血相关因子进行检测.结果 烟雾吸人后24 h,三个MP治疗组生存率显著高于s组(均P＜0.05),s+MMP组生存率(85.17％)显著高于s+HMP组、s+LMP组(65.73％和60.07％,均P＜0.05).s+MMP组、s+HMP组较s+LMP组可显著改善肺干湿比及血气变化(均P＜0.05).肺泡灌洗液(bronchoalveolarlavage fluid,BALF)检测显示,与对照组相比,烟雾吸入后组织因子(tissue factor,TF)及凝血酶抗凝血酶复合物(thrombin-antithrombin complex,TAT-c)显著升高(P＜0.01,P=0.005),凝血因子Ⅱ(factorⅡ,FⅡ)显著降低(P=0.007);给予MP干预后,TF及TAT-c显著下降,FⅡ显著回升,s+MMP、s+HMP组较s+LMP组改善更明显.对肺组织中血栓调节蛋白(thrombomodulin,TM)和TF的mRNA检测显示,烟雾吸入后,TF的表达显著升高(P＜0.01),TM的表达显著降低(P＜0.01);给予MP干预后,TM和TF的表达均显著改善,s+HMP组较s+MMP组、s+LMP组改善更显著.对外周血凝血因子检测显示,TF、纤维蛋白原(fibrinogen,FIB)和TAT-c显著升高(均P＜0.05),给予MP后FⅧ显著升高,TF在s+HMP组较s组显著升高(P＜0.01),s+MMP组、s+LMP组较s组和s+HMP组显著降低,FIB和TAT-c在各剂量MP组均显著降低,TAT-c在s+HMP组、s+MMP组较s+LMP组改善明显;对外周血中TM和内皮细胞蛋白C受体(endothelialcell protein C receptor,EPCR)检测显示,烟雾吸人后TM和EPCR显著升高(均P＜0.05),各剂量MP均可显著降低两种因子,其中s+MMP组较s+HMP组和s+LMP组效果更显著;对蛋白C(proteinC,PC％)的检测发现,烟雾吸入后PC％显著降低(P＜0.01),s+HMP组、s+MMP组可显著改善PC％水平,s+LMP组与s组差异无统计学意义;烟雾吸人后抗凝血酶Ⅲ(antithrombin,ATⅢ％)显著降低(P=0.025),三种剂量MP组均可显著提高ATⅢ％水平.结论 糖皮质激素可显著改善烟雾吸人后造成的局部及全身凝血功能紊乱,高剂量和中剂量激素效果显著.激素对凝血系统的调节是其在急性肺损伤救治中的一个重要机制.“,”Objective To explore the impact of glucocorticoid on coagulation through administrating on rats with smoke inhalation.Methods Totally 150 male S-D rats were randomly (random number) divided into 5 groups:control group (ambient air inhalation),smoke group (smoke inhalation for 30 min),smoke+high dosage methyl prednisolone group(MP 40 mg/kg,intraperitoneal injection,s+HMP group),smoke+medium dosage MP (4 mg/kg) group (s+MMP group),smoke+low dosage MP (0.4 mg/kg) group (s+LMP group) (all n=30).Survival rates were calculated 24 h after smoke inhalation.Lung tissues were collected for histopathology and wet to dry (W/D) ratio.Arterial blood was collected for blood gas test.Coagulation factors in lung and plasma were tested.Results Survival rates of three MP groups were markedly improved compared with the smoke group (all P＜0.05),and was significantly higher in the medium dosage group(85.17％) than those in the low and high dosage groups (65.73％ and 60.07％,all P＜0.05).The W/D ratio and blood gas test were markedly improved in the high and medium groups (all P＜0.05).Tissue factor (TF) and thrombin-antithrombin complex (TAT-c) in bronchoalveolar lavage fluid (BALF) increased dramatically after SI (P＜0.01,P=0.005) with a remarkable drop of factor Ⅱ (F Ⅱ) (P=0.007),all of which were attenuated by MP with dosage dependence.The mRNA expression of TF increased dramatically after SI and recovered significantly with MP administration,while the expression of thrombomodulin (TM) recovered in the opposite direction with MP,all of which were in a dosage dependent manner.TF,fibrinogen (FIB),TAT-c increased significantly in plasma after smoke inhalation (P＜0.01,P=0.027,P=0.005).F Ⅷ ％ increased with MP administration and TF was raised by high dosage MP compared with the smoke group.FIB and TAT-c were decreased in all MP groups,which were significant higher in the high and middle dosage groups.The change of TM and endothelial cell protein C receptor (EPCR) in circulation were similar with FIB or TAT-c with or without MP.Protein C (PC％) and antithrombin (AT Ⅲ ％) dropped dramatically after SI,high and middle dosages of MP could restore the activity significantly,while low dosage would restore AT Ⅲ ％ but not PC％.Conclusions Glucocorticoid can significantly improve local and systemical coagulation disorder caused by smoke inhalation,and high-and medium-dosage hormones are effective.The regulation of hormones on the coagulation system is an important mechanism in the treatment of smoke inhalation induced lung injury.