依达拉奉对急性肺损伤的治疗作用及其机制探讨

摘要

目的 探讨自由基清除剂依达拉奉对急性肺损伤大鼠模型的保护作用.方法 将32只SD大鼠随机分为C组(生理盐水+生理盐水,n=8)、E组(生理盐水+依达拉奉,n=8)、LPS组(脂多糖+生理盐水,n=8)和LPS+E组(脂多糖+依达拉奉,n=8),各组经尾静脉注入LPS和依达拉奉或等体积生理盐水.6 h后麻醉大鼠并行动脉血气分析及肺病理学检查,检测血浆中肿瘤坏死因子α(TNF-α)和白介素6(IL-6)及肺组织中丙二醛(MDA)和NO水平.结果 与C组相比,LPS组出现明显的肺损伤改变、动脉血氧分压显著下降[(99.37± 4.35) mmHg vs(60.11± 8.41) mmHg,P＜0.01]、血浆中TNF-α[(3.89± 0.53) pg/mL vs(11.95±1.97) pg/mL,P＜0.01]和IL-6[(4.73± 0.91) pg/mL vs(41.25± 7.11) pg/mL,P＜0.01]显著升高,肺组织中MDA[(2.06± 0.42) nmol/mg vs(8.91± 2.03) nmol/mg,P＜0.01]和NO[(3.97± 0.87) nmol/mg vs(8.74± 2.01) nmol/mg,P＜0.01]也显著升高;与LPS组相比,自由基清除剂依达拉奉使肺组织中MDA[(8.91± 2.03) nmol/mg vs(3.76± 0.68) nmol/mg,P＜0.01]和NO[(8.74± 2.01) nmol/mg vs(3.53± 0.71) nmol/mg,P＜0.01]显著降低,显著减轻急性肺损伤(ALI)大鼠的肺损伤程度,提高动脉血氧分压[(60.11± 8.41) mmHg vs(85.69± 6.41) mmHg,P＜0.01],并使血浆中的TNF-α[(11.95± 1.97) pg/mL vs(5.65± 1.09) pg/mL,P＜0.01]和IL-6[(41.25± 7.11) pg/mL vs(11.06± 1.27) pg/mL,P＜0.01]显著降低.结论 自由基清除剂依达拉奉能减轻急性肺损伤的病理生理变化,其机制在于依达拉奉能有效清除自由基并减少致炎因子的释放.%Objective To investigate the protective effects of edaravone on acute lung injury( ALI) model in rats. Methods Thirty-two SD rats were randomly allocated into four groups : C group( normal saline , n = 8) receiving normal saline as control ; E group( normal saline± edaravone , n = 8) receiving edaravone 15 mg/kg ; LPS group ( LPS± normal saline , n = 8) receiving LPS 6mg/kg , and LPS± E group(LPS±edaravone ,n = 8) receiving LPS 6 mg/kg and edaravone 15mg/kg. Six h later, rats were anesthetized for arterial blood gases analysis and histopathologic examinations. The TNF-α and 11_-6 levels in blood plasma and MDA and NO contents in lung tissue were measured. Results LPS induced marked lung histological injury and a significant decrease in PaO2 [(99. 37±4. 35) mmHg vs (60. 11±8. 41) mmHg,P＜0. 01]. The TNF-α levels[(3. 89±0. 53) pg/mL vs (11. 95±1. 97) pg/mL,P＜0. 01] and IL-6 levels[(4. 73±0. 91) pg/mL vs (41. 25±7. 11) pg/mL,P＜0. 01]in blood plasma and MDA contents[(2. 06±0. 42) nmol/mg vs (8. 91±2. 03) nmol/mg,P＜0. 0l]and NO contents[(3. 97±0. 87) nmol/mg vs (8. 74±2. 01) nmol/mg,P＜0. 0l]in the lung tissue were significantly increased as compared with C groups. Fdaravone increased the PaO2 [(60. 11 ± 8. 41 ) mmHg vs ( 85. 69 ± 6. 41 ) mmHg, P ＜ 0. 01] and attenuated pathohistological development of ALI. Furthermore, edaravone decreased TNF-α[(ll. 95 ± 1. 97) pg/mL vs ( 5. 65 ± 1. 09) pg/ml. , P ＜ 0. 01] , IL-6 [ ( 4l. 25 ±7. 11) pg/mL vs (11. 06±1. 27) pg/mL,P＜0. 01] ,MDA[(8. 91±2. 03) nmol/mg vs (3. 76±0. 68) nmol/mg,P＜0. 01] and NO[(8. 74±2. 01) nmol/mg vs (3. 53±0. 71) nmol/mg,P＜0. 01]. Conclusion Fdaravone attenuates pathohistological development of ALI by scavenging free radical and inhibiting proinflammatory cytokines.