Overwork induces vascular endothelial barrier dysfunction in mice
Objective To investigate the impact of overwork on vascular endothelial barrier function in mice.Methods Thirty KM mice were randomized equally into control,overwork for 2 weeks(W2)group and 4 weeks(W4)group.In the latter two groups,the mice were subjected to continuous standing in water for 8 h followed by restraint for 3 h to simulate overwork on a daily basis for 2 and 4 weeks.After modeling,4 mice from each group were intraperitoneally injected with Evans blue dye to assess vascular permeability.In the other 6 mice,serum IL-1β levels were measured using ELISA,and arterial tissues were collected for histological examination and detection of mRNA expressions of occludin,claudin-5,ZO-1,JAM-A and VE-cadherin;immunofluorescence assay was used to detect the protein expressions of claudin-5,ZO-1,VE-cadherin,and Syndecan-1.Results The mice in W2 and W4 groups exhibited slower weight gain,hair loss,reduced activity,and significantly increased serum IL-1β levels.Vascular permeability was significantly increased in W4 group.In W2 group,the endothelial cells were swollen and dissociated,and the intima was rough and irregular;arterial intimal rupture was observed in W4 group.The mRNA expressions of occludin,claudin-5,ZO-1 and JAM-A in the arterial tissues were significantly increased in W2 group but decreased in W4 group,while VE-cadherin mRNA expression were reduced in both groups(P<0.05).The protein expressions of claudin-5,ZO-1,VE-cadherin,and Syndecan-1 were all significantly reduced in W4 group.Conclusion Prolonged overwork can cause damage of the intercellular junction complexes in arterial endothelial cells and the endothelial glycocalyx to result in impaired barrier function and increased vascular permeability in mice.
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