摘要
目的 探讨利拉鲁肽对急性肺损伤(ALI)小鼠肺部炎症的影响及可能的分子机制.方法 72只小鼠随机分为Control组、ALI组、地塞米松(DXM)组、利拉鲁肽(LRLT)_L组、LRLT_M组和LRLT_H组6组.ALI组采用腹腔注射脂多糖(LPS)(15mg/kg溶于PBS),Control组仅注射等体积PBS替代LPS,DXM组在建模后腹腔注射地塞米松(5 mg/kg溶于PBS)进行治疗,LRLT_L组、LRLT_M组和LRLT_H组在建模后分别用低(10 μg/kg)、中(100 μg/kg)、高剂量(800μg/kg)利拉鲁肽进行干预.采用ELISA测量肺泡灌洗液中肿瘤坏死因子-α(TNF-α)及白细胞介素-10(IL-10)的水平.采用Western blot检测肺组织核因子-κB(NF-κB)p65的水平.结果 6组TNF-α水平差异有统计学意义(F=13.37,P＜0.05);ALI组高于Control组、LRLT_L组、LRLT_M组、LRLT_H组和DXM组,差异均有统计学意义(t=7.46、5.61、4.44、6.38、3.35,P 均＜0.01).6 组 IL-10 水平差异有统计学意义(F=66.85,P＜0.05);ALI 组高于Control组,差异有统计学意义(t=7.64,P＜0.01);ALI组低于LRLT_L组、LRLT_M组、LRLT_H组和DXM组,差异均有统计学意义(t=2.96、4.69、7.99、5.80,P均＜0.01).6组间NF-κB水平差异有统计学意义(F=47.58,P＜0.05);ALI组高于Control组,差异有统计学意义(t=10.80,P＜0.01);NF-κB的表达水平随着利拉鲁肽剂量增加而逐渐降低,LRLT_L组、LRLT_M组和LRLT_H组分别与ALI组比较,差异均有统计学意义(t=4.54、6.93、12.34,P均＜0.01);与DXM组比较,LRLT_L组和LRLT_M组的NF-κB表达均显著性增加,差异均有统计学意义(t=7.40、5.01,P均＜0.01),LRLT_H组无明显改变.结论 利拉鲁肽可促进ALI小鼠肺部的促炎因子TNF-α表达水平降低和抗炎因子IL-10表达水平升高,可能是通过下调NF-κB信号通路发挥保护作用.
Abstract
Objective To explore the effects of liraglutide on pulmonary inflammation in mice with acute lung injury(ALI)and its possible underlying mechanism.Methods A total of 72 mice were randomly divided into six groups:the control(Control)group,ALI group,dexamethasone(DXM)group,three liraglutide groups with low(LRLT_L),medium(LRLT_M)or high(LRLT_H)concentration.The ALI models of mice were established by the intraperitoneal(i.p.)injection of lipopolysaccharide(LPS)(15 mg/kg in PBS).The Control group was delivered with PBS only instead of LPS.The DXM group was injected with DXM(5 mg/kg in PBS).The LRLT_L,LRLT_M,and LRLT_H groups were respectively treated with low(10 μg/kg),medium(100 μg/kg)and high(800 μg/kg)dose of liraglutide intraperitoneally based on the ALI model.The levels of interleukin-10(IL-10)and tumor necrosis factor-α(TNF-α)in bronchoalveolar lavage fluid were determined by ELISA.The level of nuclear factor-κB(NF-κB)p65 in lung tissue was measured by Western blotting.Results The TNF-α levels were different among the six groups(F=13.37,P＜0.05);the TNF-α in the ALI group increased in comparison with that in the Control group,LRLT_L group,LRLT_M group,LRLT_H group and DXM group,all the differences were statistically significant(t=7.46,5.61,4.44,6.38,3.35;all P＜0.01).The IL-10 levels were different among the six groups(F=66.85,P＜0.05).The IL-10 in the ALI group increased compared with that in the Control group(t=7.64,P＜0.01).The IL-10 levels in DXM group,LRLT_L group,LRLT_M group,LRLT_H group were significantly higher than that in the ALI group;all the differences were statistically significant(t=2.96,4.69,7.99,5.80;all P＜0.01).The NF-κB levels were different among the six groups(F=47.58,P＜0.05).Compared with the Control group,the NF-κB levels in the ALI group was significantly higher(t=10.80,P＜0.01).The NF-κB levels,in the LRLT_L group,LRLT_M group,and LRLT_H group were gradually decreased as the dose increased of liraglutide compared with that in the ALI group;all the differences were statistically significant(t=4.54,6.93,12.34;all P＜0.01).Compared with the DXM group,the NF-κB in the LRLT_L group or LRLT_M group were up-regulated;all the differences were statistically significant(t=7.40,5.01;all P＜0.05).Whereas that in the LRLT_H group showed no significant difference.Conclusion The liraglutide could inhibit the proinflammatory factor TNF-α but promote anti-inflammatory factor IL-10 expression and secretion in the ALI mice lung,which might be mediated by the downregulation of NF-κB signaling pathway.
基金项目
广东省基础与应用基础研究基金(2019A1515110564)
NETL
NSTL
万方数据