目的探讨小窝蛋白-1(caveolin-1,Car-1)在脂多糖(hpopolysaceharide,LPS)诱导急性肺损伤(acute lung injury,ALI)大鼠肺组织中的变化。方法复制LPS致大鼠Au模型,40只SD大鼠按随机数字表法分为生理盐水对照组(Ns5mL/ks,n=8),LPS组(5mg/kgLPS尾静脉注射,分别观察3、6、24h,n=8),甲泼尼龙组(5ms/ks早泼尼龙,LPS刺激后观察6h,n=8)。分别采用Western—blot、RT—PCR、免疫组织化学法检测不同时间点肺组织中Cav-1蛋白及mRNA表达。结果LPS组大鼠肺组织病理损伤程度重,肺组织Cav-1蛋白表达明显低于对照组,Cav-1mRNA表达也低于对照组。LPS以时间依赖方式下调Cav-1蛋白(3h组:2.452±0.179,6h组:1.863±0.175,24h组:2.734±0.247)及mRNA(3h组:1.073±0.139,6h组:0.628±0.090,24h组:1.293±0.376)表达,组间比较差异有统计学意义(F值分别为23.440、47.922,均P〈0.01)。与LPS刺激6h组相比,甲泼尼龙组肺组织病理损伤程度减轻,LPS刺激下调Cav-1蛋白(1.863±0.175vs2.644.4-0.333,P〈0.01)和mRNA(0.628±0.090vs1.527±0.092,P〈0.01)表达的效应被部分抑制。结论LPS诱导Au大鼠肺组织Car-1表达下调与ALI发病密切相关,且该效应被甲泼尼龙抑制能有效地减轻肺损伤程度。
Objective To investigate the changes of caveolin - 1 ( Cav - 1 ) in the lung tissues of acute lung injury (ALI) induced by lipopolysaccharide (LPS). Methods Forty Sprague - Dawley rats were randomly (random number) divided into five groups of 8 each, including normal saline group (NS), LPS - induced ALI model groups (respectively for 3, 6 and 24 h ) and methylprednisolone group. Rats were challenged with LPS intravenously to establish the ALI model. The expression of Cav - 1 mRNA and protein in lung tissues were determined by Western - blot, reverse transcription polymerase chain reaction ( RT - PCR) and immunohistochemistry. Results In LPS - stimulated groups, lungs tissues displayed widespread pathology damage, the expression of Cav - 1 mRNA and protein were significantly lower than in NS group (2. 172 ±0. 309,3. 150 ±0. 376, respectively). LPS in a time - dependent manner down - regulated the expression of Cav - 1 protein (3 h group : 2. 452 ± 0. 179,6 h group : 1. 863 ± 0. 175,24 h group: 2. 734 ± 0.247 ) and mRNA (3 h group: 1. 073± 0. 139,6 h group: 0. 628 ± 0. 090,24 h group : 1. 293 ±0. 376) in lung. There were significant differences among the groups ( respectively, F = 23. 440, 47. 922, all P 〈 0.01 ). Compared with the group of LPS stimulation for 6 h, methylprednisolone significantly inhibited the down - regulated expression of Cav - 1 protein (1.863+0.175 vs 2.644 ±0.333, P 〈0.01) and mRNA(0. 628 ±0.090 vs 1.527 ±0.092, P〈0 01 ), and lessened the pathology damage in lung challenged by LPS. Conclusion The down - regulated expression of Cav - 1 may play important role in the development of LPS - induced ALl. Methylprednisolone can relieve LPS - induced lung injury by effectively inhibiting the down - regulated expression of Cav - 1.