摘要
目的探讨蜂毒肽MP-1对内毒素血症（ETM）小鼠急性肺损伤的保护作用。方法尾静脉注射内毒素（LPS）5mg/kg制备ETM小鼠模型。动物随机分为正常对照组（n=8）、ETM组（n=48）和MP-1治疗组（n=48,注射LPS的同时注射MP-1 3mg/kg）。ETM组和MP-1组分别于注射LPS后2、6、12、24、48、72h处死动物,采集血浆和肺组织标本,动态比浊法鲎试验检测各时相点血浆LPS水平,ELISA法检测血浆TNF-α和IL-6水平,real-ti me RT-PCR检测肺组织Toll样受体4（TLR4）、TNF-α和IL-6 mRNA表达,分光光度法检测肺组织髓过氧化物酶（MPO）活性,并观察伤后12h肺组织的病理变化。结果ETM小鼠伤后2-48h血浆LPS、TNF-α和IL-6水平显著增高（P〈0.01）,肺组织TLR4、TNF-α、IL-6 mRNA表达和MPO活性也明显增强（P〈0.05或P〈0.01）。MP-1治疗可不同程度降低血浆LPS和各细胞因子水平（P〈0.05或P〈0.01）,抑制肺组织相关基因表达及减低MPO活性（P〈0.05或P〈0.01）,并可减轻肺组织的病理损伤。结论MP-1可能通过中和LPS,减少LPS诱导的炎症介质的合成与释放,进而减轻炎症介质对肺组织的损伤。
Objective To assess the protective effect of mastoparan-1（MP-1） on acute lung injury in mouse model with endotoxemia （ETM） induced by lipopolysaccharide （LPS）, and to investigate the possible mechanism of protcetive effect. Methods The endotoxemia murine model was reproduced by tail vein injection of LPS （5mg/kg） in mice. Animals were randomly divided into normal control group （n=8）, endotoxemia group （n=48） and MP-1 treatment group （MP-1 was injected in 3mg/kg at the same time of LPS injection, n=48）. Animals of the latter two groups were sacrificed at 2, 6, 12, 24, 48 and 72 hours after injection, and then the blood and lung tissue samples were collected. Plasma LPS was assayed using kinetic turbidimetric limulus test, TNF-α and IL-6 were measured by appropriate ELISA kits, TLR4, TNF-α and IL-6 mRNA expressions in lung tissues were analyzed by real-time RT-PCR, myeloperoxidase （MPO） ac- tivity of lung tissues was determined by spectrophotometric method, and the pathological changes in lung tissues were observed under microscope. Result The plasma levels of LPS, TNF-α and IL-6 in the mice of endotoxemia group were increased at 2-48 hours after LPS injection（P〈0.01）, meanwhile, the expressions of TLR4, TNF-α and IL-6 mRNA in lung tissues were significantly elevated compared to that in normal controls （P〈0.05 or P〈0.01）. In the MP-1-treated group, however, the levels of LPS, TNF-α and IL-6 were markedly decreased （P〈0.05 or P〈0.01）, the gene expressions of TLR4, TNF-α and IL-6 in lung tissues were significantly suppressed （P〈0.05 or P〈0.01）, the MPO activity was decreased （P〈0.05 or P〈0.01） and pathological lesions in lung tissues were alleviated. Conclusion It is assumed that, by the neutralization of LPS, MP-1 may reduce the formation and release of pro-inflamrnatory mediators induced by LPS, thus alleviate the lung tissue lesions induced by the mediators.
出处
《解放军医学杂志》
CAS
CSCD
北大核心
2008年第12期1427-1430,共4页
Medical Journal of Chinese People's Liberation Army
基金
福建省青年科技人才创新项目(2008F3125)
