肥胖对非致死性肺炎小鼠肺脏炎症反应的影响

Effects of obesity on lung inflammation of nonfatal pneumonia

目的 探讨肥胖对非致死性肺炎小鼠局部组织炎症反应的影响。方法 将高脂诱导的肥胖小鼠分为I、II组,常规非肥胖小鼠分为III、IV组,I、III组滴鼻40μl含4×10^9CFU大肠杆菌的菌液,II、IV组滴鼻40μl生理盐水,于感染2、6、12、24、48、72、96 h检测各组小鼠肺脏细胞因子、炎性细胞数量和组织学变化。结果 与IV组比较,II组肺泡灌洗液中WBC、GRA、LYM、MID数量显著升高（P〈0.05或P〈0.01）,支气管及肺泡壁周围炎性细胞浸润增加,肺匀浆中TNF-α、IL-8、IL-12、MIP-2质量浓度极显著升高（P〈0.01）;感染后,I、III组肺泡灌洗液中WBC和肺匀浆中TNF-α、IL-8、IL-12、MIP-2质量浓度先升高后降低,在96 h时降至对照组水平,支气管及肺泡隔细胞浸润、炎性渗出逐渐增加,肺脏炎性损伤逐渐加重,后在96 h时见消散;与III组比较,I组在感染第2-72 h期间,肺泡灌洗液中WBC数量、细胞因子质量浓度显著升高（P〈0.05或P〈0.01）,炎性浸润更多、范围更广,96h时细胞因子质量浓度明显降低、肺泡结构恢复显著。结论 感染非致死肺炎后,肥胖能诱导更多炎性细胞和细胞因子在肺脏表达,有利于后期局部组织结构与功能的恢复。

To investigate the impact of obesity on lung inflammation in mice infected with nonfatal pneumonia, high-fat diet induced obese mice were divided into groups I, II, and the mice fed with standard diet were divided into groups III, IV. Mice in groups I and III were infused with 4＊10^9 CFU Escherichia coli （E.coli） intranasally, and mice in groups IT and IV were given the same dose of saline. Cytokines in lung homogenate, inflammatory cells in bronchoalveolar lavage fluid （BALF） and histological images of all groups were detected at 2,6,12,24,48,72,96h post-infection. The KM mice became obese after fed with high-fat diet for 8 weeks, and compared with lean controls, the counts of WBC, GRA, LYM, MID, concentrations of TNF-α, IL-8, IL-12, and MIP-2 in lung of obese mice were higher, and the inflammatory cells around the bronchia and alveoli were also more. After infection, WBC, GRA, MID in BALF and TNF-α, IL-8, IL-12, MIP-2 in lung homogenate of all mice were increased quickly, but decreased gradually, and lung lesions degree deepened gradually, and all these changes eliminated at 96 h. In comparison with lean controls, the obese mice had more WBC counts, higher cytokines concentrations and more immune cells infiltration in lung during 2-72 h period post-infection. While at 96 h post-infection, the obese individuals had lower cytokines concentrations and slighter pathological injury in lung. The results revealed that obesity can quickly raised more inflammatory cells and cytokines to the lungs to cause intense inflammation after challenge with nonfatal dose of E.coli, and it is benefit to the recovery of local tissue structure and function.