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Chinese Journal of Critical Care Medicine(Electronic Edition) ›› 2021, Vol. 14 ›› Issue (04): 281-289. doi: 10.3877/cma.j.issn.1674-6880.2021.04.004

• Original Article • Previous Articles     Next Articles

Protective effect and related mechanism of resveratrol on vascular endothelial barrier dysfunction in sepsis

Zhidong Guo1, Jinhong Wu1, Xue Zhao1, Zesheng Wu1, Yi Wang1,()   

  1. 1. Department of Emergency Medicine, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China
  • Received:2021-03-23 Online:2021-08-31 Published:2021-09-22
  • Contact: Yi Wang

Abstract:

Objective

To investigate the protective effect and related mechanism of resveratrol on lipopolysaccharide-induced vascular endothelial barrier dysfunction in sepsis.

Methods

The human umbilical vein endothelial cells (HUVECs) were divided into control, sepsis and intervention groups. The cells in the sepsis group and intervention group were stimulated with 100 μg/mL lipopolysaccharide to establish a vascular endothelial cell injury model of sepsis, and the cells in the intervention group were pretreated with resveratrol before modeling. The cell reproductive activity was detected by the cell counting kit-8 (CCK-8) and 5- ethynyl-2'-deoxyuridine (EdU), the cell migration ability was detected by the scratch test and Transwell chamber, and the adhesion rate of HUVECs to THP-1 cells was calculated in each group. The protein expression levels of CyclinD1, IQ motif containing guanosine triphosphatase activating protein 1 (IQGAP1), VE-cadherin, claudin-5, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were examined by Western-blotting, and the content of reactive oxygen species and the transfer rate of nuclear factor-kappaB (NF-κB) into the nucleus were compared among the three groups.

Results

The CCK-8 and EdU showed that the cell reproductive activity among the three group was significantly different (F= 92.460, P< 0.001; F = 40.910, P<0.001). The scratch test and Transwell chamber revealed that the cell migration ability among the three group was significantly different (F = 27.050, P<0.001; F = 56.000, P<0.001). The cell reproductive activity and cell migration ability in the control group and intervention group were higher than those in the sepsis group (all P<0.05). The adhesion rate of HUVECs to THP-1 cells (F= 19.240, P= 0.035), the protein expression of CyclinD1 (F= 115.900, P<0.001), IQGAP1 (F = 116.500, P<0.001), VE-cadherin (F = 108.500, P = 0.042), claudin-5 (F = 117.100, P = 0.028), ICAM-1 (F = 43.920, P<0.001) and VCAM-1 (F = 41.450, P = 0.046), the content of reactive oxygen species (F = 30.960, P = 0.035) and the transfer rate of NF-κB into the nucleus (F = 33.410, P = 0.028) among the three group were significantly different. Further pairwise comparison revealed that in the sepsis group, the protein expression of CyclinD1, IQGAP1, VE-cadherin and claudin-5 decreased obviously, while the adhesion rate of HUVECs to THP-1 cells, the protein expression of ICAM-1 and VCAM-1, the content of reactive oxygen species and the transfer rate of NF-κB into the nucleus increased markedly as compared with control and intervention groups (all P<0.05).

Conclusion

Resveratrol can protect the vascular endothelial barrier function in sepsis by inhibiting the accumulation of lipopolysaccharide-induced reactive oxygen species and decreasing the activation and entry of NF-κB.

Key words: Resveratrol, Sepsis, Endothelium, vascular

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