1,10邻二氮杂菲双过氧钒酸钾对脂多糖诱导的小鼠急性肺损伤的干预作用

Effect of BPV on Lipopolysaccharide-induced Acute Lung Injury in Mice

目的探讨1,10邻二氮杂菲双过氧钒酸钾[BPV(phen)]在脂多糖(LPS)诱导的小鼠急性肺损伤中的作用。方法取18只雄性C57BL/6小鼠随机分为三组:空白对照组、LPS组、BPV(phen)+LPS组。除空白对照组外,其他两组小鼠气管滴注含LPS(3mg·kg-1)的生理盐水溶液100μL,BPV (phen)+LPS组在给予LPS前30min时,腹腔给予0.4μmol·L-1 BPV(phen) 500μL,空白对照组和LPS组则腹腔给予等量生理盐水。给予LPS 24h后,处死小鼠,留取肺组织备用。肺组织切片HE染色评估肺损伤程度;Western blot法检测肺组织中Bax、Bcl-2、Cleaved caspase-3和SP-C的表达;TUNEL染色检测肺上皮细胞凋亡,ELISA法检测肺组织髓过氧化物酶(MPO)活性。结果与对照组相比,LPS处理24h后,肺上皮细胞凋亡增多,肺组织Bax和Cleaved caspase-3蛋白表达增加,肺组织Bcl-2和SP-C表达减少,肺组织MPO活性增加(P均<0.05);BPV(phen)能降低LPS引起的急性肺损伤和肺上皮细胞凋亡,降低肺组织Bax和Cleaved caspase-3蛋白表达,增加肺组织Bcl-2和SP-C蛋白表达,降低肺组织MPO活性(P均<0.05)。结论 BPV(phen)对LPS诱导的急性肺损伤有保护作用,可能是通过抑制肺上皮细胞凋亡实现的。

Objective To investigate the role of potassium 1,10-phenanthrene peroxide vanadate[BPV(phen)]in acute lung injury(ALI)induced by lipopolysaccharide(LPS)in mice.Methods 18 male C57BL/6 mice were randomly divided into 3 groups:blank control group,LPS group and BPV(phen)+LPS group.Except for the blank control group,the other two groups of mice were intratracheally dripped with 100mL of saline solution containing LPS(3mg·kg^-1).After LPS administration for 30 minutes,the BPV(phen)+LPS group mice were intraperitoneally administered with 500μL 0.4mol·L^-1 BPV(phen),while the blank control group and LPS group were intraperitoneally administered with the same amount of saline.After given LPS for 24h,the mice were sacrificed and the lungs were left for reserve.The expression of Bax,Bcl-2,Cleaved caspase-3 and SP-C in lung tissue was detected by Western blot,apoptosis of lung epithelial cells was detected by TUNEL staining and myeloperoxidase(MPO)activity was detected by ELISA.Results Compared with the control group,after LPS treatment for 24 hours,the apoptosis of lung epithelial cells increased,the expression of Bax and C leaved caspase-3 protein increased,the expression of Bcl-2 and SP-C in lung tissue decreased,and the activity of MPO in lung tissue increased(P all<0.05).BPV(phen)could reduce the acute lung injury and apoptosis of lung epithelial cells induced by LPS,and the expression of Bax and C leaved caspase-3 in lung tissue decreased,increase the expression of Bcl-2 and SP-C protein in lung tissue,and decrease the MPO activity in lung tissue(P<0.05).Conclusion The protective role of BPV(phen)in LPS-induced ALI may be associated with lung epithelial cell apoptosis.