摘要
目的 探讨抑肽酶对全氟异丁烯（PFIB）诱导的大鼠急性肺损伤（ALI）的作用.方法 成年雄性SD大鼠40只,随机分成正常对照组、ALI组和低剂量抑肽酶组（低剂量Apro组）、中剂量抑肽酶组（中剂量Apro组）、高剂量抑肽酶组（高剂量Apro组）,后4组动物均经全身暴露于自制PFIB动态吸入染毒系统5 min,染毒30 min后经腹腔注射抑肽酶或生理盐水.24 h后结束实验,并检测肺湿重与肺干重比（W/D）,支气管肺泡灌洗液（BALF）总蛋白浓度,血中IL-6、TNF-α浓度,肺组织匀浆中性粒细胞弹性蛋白酶（NE）,肺组织中NF-κB蛋白的表达情况,及光镜下肺组织病理检查,并进行统计学分析.结果 ALI组、低剂量Apro组、中剂量Apro组的W/D、总蛋白浓度、IL-6、TNF-α、NE明显升高,与对照组比较差异有统计学意义（P＜0.05）,高剂量Apro组W/D、总蛋白含量、IL-6、TNF-α、NE均低于ALI组、低剂量Apro组、中剂量Apro组（P＜0.05）;不同剂量Apro组NF-κB蛋白均较ALI组明显低表达;肺组织病理组织学显示,抑肽酶能明显改善肺组织病理损伤,以高剂量最有效.结论 高剂量Apro可明显减轻PFIB诱导ALI大鼠的肺部炎症反应,中低剂量作用不明显,其作用机制与通过降低蛋白酶的活性,抑制炎症介质的释放和抑制NF-κB的表达有关.
Objective To investigate the anti-inflammatory effects of aprotinin on acute lung injury induced by perfluoroisobutylene （PFIB） in rats.Methods Fourty male Sprague-Dawley rats were randomly divided into normal control group,acute lung injury （ALI） group,low-dose aprotinin group,middle-dose aprotinin group and high-dose aprotinin group.The later four groups of animals were exposed by whole body inhalation PFIB by homemade dynamic system for 5 minutes.Aprotinin or saline were injected by intraperitoneal injection after 30 minutes later.The experiment lasted for 24 hours,then the lung wet-to-dry weight ratio （W / D）,the levels of total protein,IL-6,TNF-α and neutrophil elastase （NE） in bronchoalveolar lavage fluid （BALF）,the expression of NF-κB in lung tissue homogenate were detected.The pathological changes of lung tissue were examined with light microscope.All the values were analyzed statistically.Results The lung W/D,the levels of total protein,IL-6,TNF-α and NE in BALF were significantly higher in ALI group,low-dose and middle-dose aprotinin group,compared with the control group （P ＜ 0.05）.The lung W/D and the levels of total protein,IL-6,TNF-α and NE in BALF of high-dose aprotinin group were significantly lower than those in ALI group,low-dose and middle-dose aprotinin group （All P ＜ 0.05）.The expression of NF-κB protein in different doses of aprotinin group was significantly lower than that in ALI group.Lung tissue histopathology showed aprotinin can significantly improve lung tissue damage;high-dose group showed the most significant effect against lung tissue damage.Conclusion High-dose aprotinin can significantly reduce inflammatory response in ALl rats induced by PFIB,but there is no obvious effect in low-dose and middle-dose aprotinin.The mechanism of the antiinflammatory effect of aprotinin is associated with reducing protease activity,inhibiting the release of inflammatory mediators and inhibiting the expression of NF-κB.
出处
《中国急救医学》
CAS
CSCD
北大核心
2014年第6期533-537,I0002,共6页
Chinese Journal of Critical Care Medicine
