The effect of heparin on vascular endothelial cell injury induced by lipopolysaccharide in rats and the study of nuclear factor-κB, interleukin-1β, interleukin-6, tumor necrosis factor-α

Abstract

Objective To investigate the effect of heparin on vascular endothelial cell injury induced by lipopolysaccharide in rats, and the changes of the levels of nuclear factor-κB (NF-κB), interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α. Methods 90 SD rats were randomly divided into three groups: LPS group, heparin group and control group, 30 rats in each group. Rats in the LPS group and heparin group were injected with 10 mg/kg by intraperitoneal injection of lipopolysaccharide solution to establish sepsis model. The heparin group was injected with 300 IU/kg heparin solution before 1H injection. Rats in control group were injected with NaCl solution by intraperitoneal injection in accordance with 10 mg/kg. The morphological changes of lung tissue in rats at 6 h were compared. The changes of NF-κB, IL-1β, IL-6, TNF-α in three groups were detected by enzyme linked immunosorbent assay. The pulmonary vascular permeability changes of rats were detected by Evans blue (EB). Results In Lipopolysaccharide group and heparin group 0 h to 6 h nf-kappa B significantly increased activity of lipopolysaccharide group by 0 h (2.51±0.49) U/L up to 6 h (18.85±2.97) U/L, heparin group by 0 h (2.39±0.34) U/L up to 6 h (3.37±0.82) U/L, lipopolysaccharide group nf-kappa B increased activity levels compared with heparin group is more significant (P=0.021); 6 to 12 h h two groups the nf-kappa B activity significantly decreased (P<0.05), of which the lipopolysaccharide group by 0 h (18.85±2.97) U/L fell to 6 h (13.47±2.19) U/L (P=0.022), heparin group by 0 h (3.37±0.82) U/L fell to 6 h (2.25±0.34) U/L (P=0.048), but it is still significantly higher than the control group, and 0 h level (P=0.000); 0 h three groups of blood beta, IL-6, IL-1β, TNF-α level difference was not significant (IL-1 beta: P=0.940; IL-6: P=0.626; TNF-α: P=0.948), and 0 h to 6 h, lipopolysaccharide group and heparin group rats each index in the blood rise rapidly (within the group, compared with 0 h, 6 h, lipopolysaccharide group, IL-1β: P=0.039; IL-6: P=0.018; TNF-α: P=0.000; heparin group, IL-1β: P=0.036; IL-6: P=0.036; TNF-α: P=0.012), the index level significantly dropped 12 h (comparison group, compared with 6 h, lipopolysaccharide group, IL-1 beta: P=0.042; IL-6: P=0.027; TNF-α: P=0.008; heparin group, IL-1β: P=0.047; IL-6: P=0.045; TNF-α: P=0.034). Lipopolysaccharide group 6 h and 12 h of the blood of rats beta, IL-6, IL-1 TNF-αlevel was significantly higher than that of heparin group (lipopolysaccharide group: heparin group, 6 h, IL-1β: P=0.031; IL-6: P=0.023; TNF-α: P=0.000; 12 h, IL-1β: P=0.046; IL-6: P=0.038; TNF-α: P=0.017). (3) the contents of rat lung EN heparin [(1.21±0.18) mg/ml], and significantly lower than the lipopolysaccharide group [(1.92±0.20) mg/ml] (t=-8.344, P=0.000). Conclusion The heparin can inhibit the damage of vascular endothelial cells by inhibiting the levels of NF-κB, IL-1β, IL-6 , TNF-α in sepsis rats, and thus play an anti-inflammatory role in sepsis. Key words: Heparin; Lipopolysaccharide; Sepsis; Vascular endothelial cell injury