叶黄素对脂多糖致小鼠急性肺损伤保护作用

Study on protective effects of lutein on acute lung injury induced by lipopolysaccharide in mice

目的研究叶黄素对脂多糖(LPS)所致小鼠急性肺损伤(ALI)的保护作用。方法雄性昆明种小鼠60只,随机分为正常对照组、急性肺损伤模型组、地塞米松阳性对照组(5mg/kg)以及叶黄素低、中、高剂量组(10,15,20mg/kg)共6组。不同剂量叶黄素给大鼠连续灌胃30d后,腹腔注射脂多糖6.0mg/kg建立ALI模型。在注射后6h,收集腹主动脉血并进行左侧支气管肺泡原位灌洗以收集灌洗液,测定血中淋巴细胞亚群CD3+、CD4+、CD8+、肿瘤坏死因子α(TNF-α)、白细胞介素8(IL-8)及丙二醛(MDA)及超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)活性;测定各组的肺湿重/干重比、肺组织中性粒细胞髓过氧化物酶(MPO)含量及肺组织匀浆TNF-α、白细胞介素10(IL-10)含量。结果叶黄素各剂量组的血TNF-α含量由低到高依次为(390.10±81.50),(374.20±80.09),(340.18±84.39)ng/L,低于模型组(475.29±93.12)ng/L;IL-8含量由低到高依次为(111.13±16.30),(107.33±15.39),(103.39±14.36)ng/L,低于模型组(124.56±20.21)ng/L;MPO含量由低到高依次为(5.12±1.02),(5.03±0.80),(4.48±0.73)U/g低于模型组(6.02±1.06)U/g;MDA含量由低到高依次为:(9.20±0.62),(8.29±1.30),(7.10±1.21)nmol/(mgpro),低于模型组(11.28±2.14)nmol/(mgpro);肺组织湿重/干重比亦低于对照组,差异均有统计学意义(P<0.001),表明叶黄素各剂量组均可降低LPS诱发的过氧化反应。同时叶黄素各剂量组的IL-10含量由低到高依次为(71.23±22.39),(78.28±21.27),(85.18±28.15)ng/L,高于模型组(60.13±20.28)ng/L;血SOD含量由低到高依次为(114.30±41.50),(130.53±40.23),(149.19±41.77)U/(mgpro),高于模型组(74.52±24.40)U/(mgpro);GSH-Px活性由低到高依次为(77.70±12.15),(85.20±12.03),(90.47±13.12)U/(mgpro),高于模型组(62.24±10.13)U/(mgpro);并改善血中淋巴细胞亚群分布;差异均有统计学意义(P<0.001),表明叶黄素各剂量组均可拮抗LPS引起的抗氧化机制的损伤。结论叶黄素对LPS所致急性肺损伤具有预防性保护作用。

Objective To study the protective effects of lutein against acute lung injury induced by lipopolysaccharide and its possible mechanism in mice. Methods Randomly distributed 60 male Kunming mices into control group, lipopolysaccharide-induced acute lung injury model group （ALI）, dexamethasone （DXM） group （ 5 mg/kg） and low, middle, high dose groups of lutein （ 10,15,20 mg/kg）. After 30d with different dosage of lutein ,control group was given physiological saline, ALl model group, lutein administrated groups and DXM group were injected with lipopolysaccharide （LPS） （6.0 mg/kg） to induce ALI. Six hours after the injection,abdominal aorta blood was collected for measuring of lymphocyte subpopulations （ CD3^＋ , CD4^＋ , CD8^＋ ）, tumour factor-α （ TNF-α）, leckocyte interpose-8 （ IL-8 ）, malondialdehyde （ MDA ） content, superoxide dismutase（ SOD）, glutathione perioxidase（GSH-Px） activities. And lung wet weight/dry weight ratio, neutrophil MPO activity of lung TNF-α, leckocyte interpose-10 （IL-10） content of lung were measured. Results Treatment with different dosage of lutein could significantly decrease serum TNF - α（ model group ：475.29 ± 93.12; lutein groups from low dose to high dose ： 390. 10 ± 81.50,374. 20 ± 80. 09,340. 18 ± 84. 39 ） ; IL - 8 （ model group： 124. 56 ± 20. 21 ; lutein groups from low dose to high dose ： 111.13 ± 16. 30,107.33 ± 15.39,103.39 ± 14. 36 ） ; MPO（ model group ： 6. 02 ± 1.06 ; lutein groups from low dose to high dose ： 5.12 ± 1.02,5.03 ± 0. 80,4. 48 ± 0. 73 ） ; MDA content （ model group： 11.28 ± 2. 14 ;lutein groups from low dose to high dose ：9.20 ± 0.62,8.29 ± 1.30,7.10 ± 1.21 ）. There was a reduction of IL-10 in lung（model group： 60. 13 ± 20. 28; lutein groups from low dose to high dose：71.23 ± 22. 39,78.28 ± 21.27,85. 18 ± 28. 15 ）. The concentrations of SOD were （ model group ：74.52 ± 24.40 ; lutein groups from low dose to high dose ： 114. 30 ± 41.50,130. 53 ± 40. 23,149.19 v 41.77 ）. GSH-Px activities were （ model group： 62. 24 ± 10. 13 ; lutein groups from low dose to high dose：77. 70 ± 12. 15,85.20 ± 12. 03,90. 47 ± 13. 12）. The lymphocyte subpopulations of the blood was improved. Conclusion Lutein showed protective effects on the acute lung injury induce by LPS in mice.