Objective To investigate the effect of resveratrol on changes of nuclear factor-κB (NF-κB)and inflammatory reaction in mice with acute lung injury(ALI)induced by lipopolysaccharide (LPS). Methods According to random number table method,32 male ICR mice were divided into four groups:control,model,resveratrol pretreatment and dexamethasone positive control groups(each,n=8). The mice in the resveratrol pretreatment group were orally gavaged with 25 mg/kg resveratrol for 3 days before injection with LPS,10 mg/kg of dexamethasone was injected intra-peritoneally for 3 days in the positive control group,and 1 ml of normal saline was gavaged for 3 days in the control and model groups. On the 4th day,LPS 15 mg/kg was injected via a tail vein in the above three groups,while in the control group,the same amount of normal saline was injected into the vein,and after 8 hours,the mice were sacrificed. The lung wet/dry weight(W/D) ratio and hematoxylin-eosin(HE)staining for investigation of the histopathologic changes of lung tissues were carried out. The Western blotting was used to detect the protein expression of NF-κB p65,real-time fluorescein quantitative polymerase chain reaction(PCR)was applied to assay the expression of interleukin-1β(IL-1β) mRNA and macrophage inflammatory protein-1α(MIP-1α) mRNA in lung tissue. Results Compared with the control group,in the model group,there was significant lung structural damage,the histological results showed pulmonary alveolar hemorrhage,edema and inflammatory cell infiltration;the lung W/D ratio,the activity and its expression of NF-κB,the expressions of IL-1βand MIP-1αmRNA in lung tissue were significantly increased (all P<0.01). Compared with the model group,the lung histopathological changes were much more ameliorated, and the W/D ratio(5.23±0.15,5.21±0.21 vs. 5.48±0.14),the activity of NF-κB p65 protein(1.25±0.09, 1.09±0.04 vs. 1.52±0.10),the mRNA expressions of IL-1β(11.10±2.84,5.10±0.82 vs. 23.00±4.25)and MIP-1α(29.01±5.81,12.30±0.95 vs. 60.27±5.62)were markedly suppressed in resveratrol pretreatment group and dexamethasone positive control group(all P<0.01). Conclusion Resveratrol has remarkable protective effect on ALI induced by LPS in mice,its mechanism is possibly related to the inhibition of NF-κB activation and reduction of inflammatory response in the lung tissue.% 目的研究白藜芦醇对内毒素脂多糖(LPS)诱导的急性肺损伤(ALI)小鼠核转录因子-κB (NF-κB)及炎症反应的影响.方法雄性ICR小鼠32只,按随机数字表法分为对照组、模型组、白藜芦醇预处理组、地塞米松阳性对照组,每组8只.白藜芦醇预处理组以白藜芦醇25 mg/kg灌胃,地塞米松阳性对照组腹腔注射地塞米松10 mg/kg,对照组、模型组灌胃1 ml生理盐水,共3 d.第4日尾静脉注射LPS 15 mg/kg,对照组注射等量生理盐水,8 h后处死小鼠.检测肺组织湿/干质量(W/D)比值、苏木素-伊红(HE)染色观察肺组织病理学变化,蛋白质免疫印迹法(Western blotting)检测NF-κB p65蛋白表达,实时荧光定量聚合酶链反应(PCR)检测白细胞介素-1β(IL-1β)、巨噬细胞炎性蛋白-1α(MIP-1α)的mRNA表达.结果与对照组比较,模型组小鼠肺损伤明显,肺泡内出血、水肿、炎性细胞浸润,肺组织W/D比值增加,NF-κB活化表达明显增加,肺组织IL-1β和MIP-1αmRNA表达均明显增加(均P<0.01).与模型组比较,白藜芦醇预处理组、地塞米松阳性对照组肺组织病理损伤程度明显减轻,肺组织W/D比值(5.23±0.15、5.21±0.21比5.48±0.14)、NF-κB p65蛋白(1.25±0.09、1.09±0.04比1.52±0.10),IL-1βmRNA(11.10±2.84、5.10±0.82比23.00±4.25)和MIP-1αmRNA(29.01±5.81、12.30±0.95比60.27±5.62)相对表达量均明显降低(均P<0.01).结论白藜芦醇对内毒素性ALI有显著的保护作用,其作用机制可能与其抑制NF-κB活化、降低肺组织炎症反应有关.
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