Wang Zong-yu, Wu Sheng-nan, Zhu Xi
Department of Critical Care Medicine, Peking University, Beijing, China.
Zhongguo Wei Zhong Bing Ji Jiu Yi Xue. 2012 Oct;24(10):612-5.
To observe the effects of three dosages of nebulized unfractionated 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.
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.
At 6 hours after LPS-induced lung injury, the levels of TATc and TNF-α, 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 μg/L, 1.165±0.854 μg/L vs. 2.141±0.791 μg/L, TNF-α: 4.449±5.054 ng/L, 9.096±4.099 ng/L vs. 18.184±3.869 ng/L, 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-αlevel in BALF, 18 U/g group evidently exceeded that of 6 U/g group (15.503±8.753 ng/L vs. 4.449±5.054 ng/L, 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).
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.
观察三种剂量雾化普通肝素（UFH）对内毒素诱导的急性肺损伤大鼠模型肺泡凝血、炎症及肺组织学的影响，探讨局部应用UFH治疗肺内凝血功能障碍的合适剂量。
将29只雄性Wistar大鼠按随机数字表法分为对照组（n = 5）和UFH组（n = 24），经静脉注射脂多糖（LPS）复制内毒素诱导的ALI大鼠模型。UFH组再分为三个亚组，分别于激发后2小时给予10 ml含6、12和18 U/g雾化UFH一次，对照组仅用生理盐水雾化。所有大鼠于静脉注射LPS后6小时处死，行支气管肺泡灌洗并收集灌洗液。采用酶联免疫吸附测定（ELISA）法检测支气管肺泡灌洗液（BALF）中凝血酶 - 抗凝血酶复合物（TATc）、肿瘤坏死因子 -α（TNF -α）水平，并记录肺湿/干（W/D）重比、组织学评分。
LPS诱导肺损伤后6小时，6 U/g和12 U/g组的TATc、TNF -α水平、肺W/D重比及组织学评分均显著低于对照组（TATc：0.959±0.681 μg/L、1.165±0.854 μg/L比2.141±0.791 μg/L；TNF -α：4.449±5.054 ng/L、9.096±4.099 ng/L比18.184±3.869 ng/L；W/D重比：7.018±1.137、7.367±0.349比8.472±0.614；组织学评分：16.0±1.0、16.5±1.5比19.6±0.4，P<0.05或P<0.01）。UFH各亚组间BALF中TATc水平及肺组织学评分比较差异无统计学意义。对于BALF中TNF -α水平，18 U/g组明显高于6 U/g组（15.503±8.753 ng/L比4.449±5.054 ng/L，P<0.01），18 U/g组肺W/D重比也显著高于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）。
ALI治疗中雾化UFH剂量以不超过12 U/g为宜，该剂量足以抑制肺泡凝血级联反应，降低早期炎症反应，减轻肺组织损伤。
