摘要目的 通过比较雾化吸入不同剂量普通肝素(UFH)对内毒素致急性肺损伤(ALI)大鼠肺部凝血、炎症和肺损伤组织学的效应,探讨UFH局部给药干预肺内凝血病的合适剂量.方法 29只雄性Wistar大鼠经尾静脉注射大肠杆菌脂多糖(LPS)复制ALI模型,按随机数字表法分为对照组(5只)和UFH组(24只).UFH组于制模后2h分别给予6、12、18 U/g的UFH 10 ml雾化吸入1次实施干预,而对照组则仅用生理盐水进行雾化吸入.LPS注射后6h处死大鼠,进行肺泡灌洗,收集支气管肺泡灌洗液(BALF).采用酶联免疫吸附试验( ELISA)检测凝血酶-抗凝血酶复合物(TATc)、肿瘤坏死因子-α(TNF-α)水平；计算肺组织湿/干重(W/D)比值,并进行肺损伤病理评分.结果 UFH 6 U/g和12 U/g组BALF中TATc(μg/L)、TNF-α(ng/L)以及肺组织W/D比值、病理评分(分)均明显低于对照组(TATc:0.959±0.681、1.165±0.854比2.141±0.791,TNF-α:4.449±5.054、9.096±4.099比18.184±3.869,W/D比值:7.018±1.137、7.367±0.349比8.472±0.614,病理评分:16.0±1.0、16.5±1.5比19.6±0.4,P＜0.05或P＜0.01).UFH不同剂量组间BALF中TATc水平和病理评分无差异；UFH 18 U/g组BALF中TNF-α明显高于UFH 6 U/g组(15.503±8.753比4.449±5.054,P＜0.01)；UFH18 U/g组肺组织W/D比值明显高于UFH 6 U/g组(8.850±1.157比7.018±1.137,P＜0.05)和12 U/g组(8.850±1.157比7.367±0.349,P＜0.05).结论 雾化吸入不超过12 U/g剂量的UFH治疗ALI时,能够抑制肺泡局部高凝状态,减轻早期炎症反应和肺组织损伤.

abstractsObjective To observe the effects of three dosages of nebulized unfractioned heparin (UFH) on alveolar coagulation,inflammation and lung histology in endotoxin-induced acute lung injury rat model,and investigate the appropriated dose of local UFH in managing intrapulmonary coagulopathy.Methods Twenty-nine male Wistar rats were divided into control (n=5) and UFH group (n=24) in table of random number,which were duplicated to be endotoxin-induced ALI rat model with lipopolysaccharide (LPS) injecting by intravenous route.The UFH group was divided into three subgroups,which were administered once with 6,12 and 18 U/g aerosolized UFH in 10 ml at 2 hours after challenge,respectively,while the control group was simply nebulized with normal saline.All rats were sacrificed at 6 hours after intravenous administration of LPS,bronchoalveolar lavage was performed,and the fluid was collected.Enzyme-linked immune sorbent assay (ELISA) was used to measure the level of thrombin-antithrombin complex (TATc),tumor necrosis factor-α (TNF-α) in bronchoalveolar lavage fluid (BALF),and lung wet/dry (W/D) weight ratio,histology score were recorded.Results At 6 hours after LPS-induced lung injury,the levels of TATc (μg/L) and TNF-α (ng/L),lung W/D weight ratio and histology score in 6 U/g and 12 U/g group were all lower than those of control group significantly (TATc:0.959 ± 0.681,1.165 ± 0.854 vs.2.141 ± 0.791,TNF-α:4.449 ± 5.054,9.096 ±4.099 vs.18.184 ± 3.869,W/D weight ratio:7.018 ± 1.137,7.367 ± 0.349 vs.8.472 ± 0.614,histology score:16.0 ±1.0,16.5 ± 1.5 vs.19.6 ± 0.4,P＜0.05 or P＜0.01 ).There was no significant difference in the comparisons between the subgroups of UFH in TATc level in BALF and lung histology score.For the TNF-α level in BALF,18 U/g group evidently exceeded that of 6 U/g group ( 15.503 ± 8.753 vs.4.449 ± 5.054,P＜0.01 ),and lung W/D weight ratio in 18 U/g group was also significantly higher comparing to 6 U/g (8.850 ± 1.157 vs.7.018 ± 1.137,P＜0.05 ) and 12 U/g group ( 8.850 ± 1.157 vs.7.367 ± 0.349,P＜0.05 ).Conclusion It was appropriate for the dose of nebulized UFH to be administered no more than 12 U/g in ALI treatment,which was enough to inhibit alveolar coagulant cascade,decrease early inflammatory response and alleviate lung tissue injury.