摘要
目的研究肥胖对致死性肺炎小鼠肺脏炎症反应的影响。方法将高脂诱导的肥胖小鼠分为Ⅰ、Ⅱ组,非肥胖小鼠分为Ⅲ、Ⅳ组,Ⅰ、Ⅲ组滴鼻40μl含4×1010CFU大肠杆菌菌液;Ⅱ、Ⅳ组滴鼻40μl生理盐水。观察感染前(0 h)及感染后2、6、12、24、48、72、96 h各组小鼠的存活率并检测各组小鼠肺脏炎性细胞数量、细胞因子和组织学变化。结果试验期内,Ⅰ组小鼠的总死亡率高于Ⅲ组,但感染12 h内,Ⅰ组小鼠的死亡率低于Ⅲ组。整个试验期内,Ⅱ组小鼠肺泡灌洗液中的WBC数量,以及肺组织匀浆中TNF-α、IL-8、IL-12、MIP-2及RETN的质量浓度均显著高于Ⅳ组(P<0.05或P<0.01),支气管及肺泡壁周围浸润炎性细胞也较Ⅳ组明显增多。Ⅰ组的WBC、MID在6~12 h,GRA在2~24 h,LYM在2~12 h,TNF-α、IL-12、RETN在2~96 h,IL-8在6~96 h,MIP-2在2~72 h均显著升高(P<0.01或P<0.05)。与Ⅳ组比较,Ⅲ组的WBC、MID在6~12 h,GRA在6~24 h,LYM在6 h,TNF-α、IL-12、RETN在2~96 h,IL-8、MIP-2在6~96 h极显著升高(P<0.01)。与Ⅲ组比较,Ⅰ组WBC在0~6 h,GRA在0~12 h,LYM在2 h,MID在0、6 h,TNF-α在0~6 h,IL-8在6~24 h,IL-12在0~2 h、24~72 h,MIP-2在0~24 h,RETN在0~2 h、24~48 h均显著升高(P<0.01或P<0.05),感染24 h的肺泡及支气管周围炎性细胞浸润更丰富,范围更广,组织结构被破坏得更严重,感染96 h的肺组织中炎性细胞仍较多,肺泡壁增厚更明显。结论感染致死性剂量大肠杆菌后,肥胖能诱导更多的炎性细胞在肺脏积聚,增强清除病原的能力,但大量炎性细胞浸润后,释放大量的炎症细胞因子如TNF-α、IL-8、RETN、MIP-2等,加重了肺部的炎症反应,进而损伤呼吸功能,从而更容易导致小鼠死亡,引起死亡率增高。
This study designed to investigate the impact of obesity on lung inflammation in mice infected with fatal pneumonia.High-fat diet induced obese mice were divided into groups Ⅰ,Ⅱ,non-obese mice were divided into groups Ⅲ,Ⅳ.Groups Ⅰ,Ⅲ were infused with 4×10^（10） CFU Escherichia coli（E.coli） intranasally,and groups Ⅱ,Ⅳ were given the same dose of saline.We observed the survival rate of mice and detected the inflammatory cells,cytokines and histological changes in each group at 0,2,6,12,24,48,72,96 h after infection.Data showed that the total mortality rate of group Ⅰ was higher than that in group Ⅲ during the trial period,but the mortality rate of groupⅠ was lower than group Ⅲ within 12 h infection.The WBC,TNF-α,IL-8,IL-12,MIP-2 and RETN of group Ⅱwere all higher than those of group IV during the whole trial period（P〈0.05 or P〈0.01）,while the inflammatory cells around the bronchia and alveoli wall were also increased compared with group Ⅳ.Compared with group Ⅱ,the WBC,MID in 6-12 h,GRA in 2-24 h,LYM in 2-12 h,TNF-α,IL-12,RETN in 6-96 h,IL-8 in 6-96 h,MIP-2 in2-72 h in group I were all significantly increased（P〈0.01 or P〈0.05）.Compared with group IV,the WBC,MID in6-12 h,GRA in 6-24 h,LYM at 6 h,TNF-α,IL-12,RETN in 2-96 h,IL-8,MIP-2 in 6-96 h in group Ⅲ were extremely increased（P〈0.01）.Compared with group Ⅲ,the WBC in 0-6 h,GRA in 0-12 h,MID at 0 h,6 h,LYM at2 h,TNF-α in 0-6 h,IL-8 in 6-24 h,IL-12 in 0-2 h,24-72 h,MIP-2 in 0-24 h,RETN in 0-2 h,24-48 h in group I were all significantly increased（P〈0.01 or P〈0.05）.At 24 h,the inflammatory cell infiltration in the alveolar and bronchus were more abundant,the scope was wider,and the tissue structure was damaged more seriously.At 96 h,inflammatory cells in the lung tissue were still more,and alveolar wall thickening was more obvious.The results revealed that obesity can induce the accumulation of inflammatory cells in lung,enhance the ability of removing pathogens in lethal-dose E.coli infection.While,with a large number of inflammatory cells infiltration,the releasing of inflammatory cytokines like TNF-α,IL-8,RETN,MIP-2,etc.are increased,which exacerbate lung inflammation,then damage the respiratory function,thus increases the mortality in mice.
出处
《免疫学杂志》
CAS
CSCD
北大核心
2016年第11期941-946,共6页
Immunological Journal
基金
四川省科技厅支撑项目(2013NZ0032)
关键词
肥胖
致死性
肺炎
死亡率
炎症细胞因子
Obesity
Mortality
Pneumonia
Mortality rate
Inflammatory cytokines
