外源性ghrelin在脓毒症小鼠肺脏炎症反应中的作用

摘要

目的：探讨生长素释放肽（ghrelin）在脓毒症小鼠肺脏炎症反应中的作用机制。方法①通过腹腔注射内毒素（LPS）建立脓毒症模型，采用腹腔注射外源性ghrelin 200μg/kg进行干预。选取雌性昆明小鼠54只，随机分为对照组、模型组及ghrelin干预组，每组18只，对照组经腹腔注射等量生理盐水；模型组经腹腔内注射脂多糖6mg/kg；干预组先经腹腔注射入外源性ghrelin 200μg/kg，30min后再经腹腔注射脂多糖6mg/kg；②各组分别于3h、9h及18h随机处死6只小鼠，留取肺组织标本行HE染色，观察肺组织病理变化；ELISA法测定炎症因子TNF-α、IL-6的表达量；③统计分析使用SPSS 17.0软件，所得数据以x±s表示，用单因素方差分析来比较组之间总体差异,用SNK方法比较每两组的差异。结果与对照组相比，模型组及干预组中肺组织病理炎症反应加重，相关炎症因子TNF-α、IL-6的表达水平在各时间点均明显升高（P均<0.05），差异有统计学意义；与模型组相比，干预组中肺组织病理炎症反应减轻，相关炎症因子TNF-α、IL-6的表达水平在各时间点均明显降低（P均<0.05），差异有统计学意义。结论外源性ghrelin可通过降低早期炎症因子TNF-α、IL-6的表达，从而减轻脓毒症小鼠肺脏炎症反应，在脓毒症肺脏炎症反应中发挥保护作用。%Objective To discuss the regulating role of ghrelin in lung inflammatory response of mice with sepsis. Methods ①Set up sepsis model by injecting endotoxin into enterocoelia of mice, while injecting ghrelin (200μg/kg) into en-terocoelia of mice as intervention treatment , intraperitoneal injection equivalent amount of saline as a control was injected into enterocoelia of mice. 54 female Kunming mice were randomly divided into control group , model group and intervention group with ghrelin, each group contained 18 mice. Saline was injected into abdominal cavity of mice in control group. Model group with treated lipopolysaccharide 6mg/kg was injected into abdominal cavity. Intervention group: injected the ghrelin 200μg/kg into abdominal cavity, then injected lipopolysaccharide 6mg/kg into the abdominal cavity of mice after 30min. ②Six mice of each group were executed randomly respectively in 3h, 9h and 18h, collected specimen to corresponding test. Took each experi-mental group organization of the right upper lobe for HE staining , then observed the lung tissue pathology. Used enzyme linked immunosorbent (ELISA) to determinate the expression level of TNF alpha, IL-6.③The software of SPSS 17.0 was applicated for statistical analysis of data which was expressed with x±s. Comparison between groups was used by single factor analysis of vari-ance. Results Compared with the control group, lung tissue inflammation of model group and intervention group aggravated, the expression levels of TNF alpha, IL-6 at every time points were significantly higher (P<0.05), the difference had statistical significance. Compared with model group, lung tissue inflammation in the intervention group alleviated, the expression levels of TNF alpha, IL-6 at every time points were significantly lower (P<0.05), the difference had statistical significance. Conclusion Exogenous ghrelin can alleviate lung inflammatory response of mice with sepsis through decreasing the expression of TNF alpha and IL-6, it plays a protective role in sepsis lung inflammation.