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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。
Objective To study the effect of obesity on lung inflammation in lethal pneumonia mice. Methods The obese mice induced by hyperlipidemia were divided into groups Ⅰ and Ⅱ, and the non-obese mice were divided into groups Ⅲ and Ⅳ. The intranasal nasal mucosa of 4 × 1010CFU colonies in group Ⅰ and Ⅲ were treated with 40μl Physiological saline. The survival rates of mice in each group before and at 2, 6, 12, 24, 48, 72 and 96 h after infection were observed and the numbers of inflammatory cells, cytokines and histological changes were examined. Results In the experimental period, the total mortality of group Ⅰ was higher than that of group Ⅲ, but the mortality of group Ⅰ was lower than that of group Ⅲ within 12 h after infection. During the whole experiment period, the number of WBC in bronchoalveolar lavage fluid and the concentration of TNF-α, IL-8, IL-12, MIP-2 and RETN in lung homogenates of group Ⅱ were significantly higher than that of group Ⅳ (P <0.05 or P <0.01), infiltration of inflammatory cells around the bronchial and alveolar wall was also significantly increased compared with the group Ⅳ. In group Ⅰ, the WBC, MID were 6-12 h, GRA was 2-24 h, LYM was 2-12 h, TNF- α, IL-12, RETN were 2-96 h, IL-8 was 6-96 h, MIP-2 was significantly increased in 2-72 h (P <0.01 or P <0.05). Compared with group Ⅳ, the WBC, MID in 6 ~ 12 h, GRA in 6 ~ 24 h, LYM in 6 h, TNF-α, IL-12, RETN in 2-96 h, 2 in 6 ~ 96 h significantly increased (P <0.01). Compared with group Ⅲ, the WBC of group Ⅰ was 0-6 h, GRA was 0-12 h, LYM was 2 h, MID was 0,6 h, TNF-α was 0-6 h, IL-8 was 6-24 h (P <0.01 or P <0.05). The levels of IL-12 in 0-2 h, 24-72 h, MIP-2 at 0-24 h and RETN in 0-2 h and 24-48 h were significantly higher 24 h of alveolar and bronchial inflammatory cell infiltration is richer, broader, tissue damage was more serious, infected 96 hours of lung tissue inflammatory cells are still more obvious alveolar wall thickening. Conclusion Infected with lethal dose of Escherichia coli, obesity can induce more inflammatory cells to accumulate in the lungs and enhance the ability to clear pathogens. However, a large number of inflammatory cytokines release a large number of inflammatory cytokines such as TNF-α and IL-8 , RETN, MIP-2 and so on, aggravating the inflammatory reaction in the lungs and then damaging the respiratory function, thus making it easier for mice to die and causing an increase in mortality.