Effects of ulinastatin on adhesion molecules and endothelial function in rats with sepsis / 中国中西医结合急救杂志

ABSTRACT

Objective To approach the effect of ulinastatin (UTI) on protection of vascular endothelial cells in rats with sepsis and its mechanism.Methods Fifty-two Sprague-Dawley (SD) male rats were randomly divided into a normal saline pretreatment group (control group) and a UTI pretreatment group (UTI group), each groupn = 26. The rats in two groups were given lipopolysaccharide (LPS, 10 mg/kg) intra-peritoneal injection for the establishment of rat septic models. In UTI group, 18 hours before LPS injection, intraperitoneal injection of UTI 100 kU/kg dissolved in 5 mL normal saline was given, while in the control group, 3 hours before LPS injection, intraperitoneal injection of 5 mL normal saline was given to the rats for pretreatment. Respectively, at 0.5, 2, 4, 12, 24, 72 hours after model establishment, tail venous blood and myocardial tissue were taken. The levels of tumor necrosis factor-α (TNF-α), interleukins (IL-6, IL-10), vascular cell adhesion molecule (VCAM) and intercellular adhesion molecule-1 (ICAM-1) were detected by enzyme-linked immunosorbent assay (ELISA); the correlation between TNF-α and ICAM-1 was analyzed; the expression of ICAM-1 in myocardial cell was determined by immunohistochemistry.Results After model establishment, the levels of TNF-α, IL-6, IL-10, ICAM and VCAM in two groups were gradually increased, reaching the peaks at 24, 12, 12, 72, 72 hours, respectively. Compared with control group, the levels of TNF-α, IL-6, ICAM-1, VCAM of UTI group were significantly lower at various time points [24 hours TNF-α (ng/L) 119.8±28.9 vs. 190.2±30.4, 12 hours IL-6 (ng/L) 327.8±26.9 vs. 948.7±63.8, 72 hours VCAM (ng/L) 36.3±3.2 vs. 68.8±2.4, 72 hours ICAM-1 (ng/L) 115.6±11.6 vs. 129.4±8.2,P < 0.05 orP < 0.01], IL-10 was significantly increased [12 hours (ng/L) 80.7±1.9 vs. 42.3±4.9,P < 0.01]. TNF-αwas positively correlated to ICAM significantly (UTI groupr = 0.907,P = 0.050; control groupr = 0.961, P = 0.010). Immunohistochemistry showed that after modeling for 0.5 hour, basically no positive expression of ICAM-1 in myocardial cells was found in the two groups; in the control group, at 12 hours the positive expression of ICAM-1 was increased, and in UTI group, a little expression of ICAM-1 was seen; at 72 hours, the expression of ICAM-1 was significantly increased in both groups.Conclusion UTI can protect the function of endothelial cells in rats with sepsis by regulating the expressions of proinflammatory cytokine, anti-inflammatory cytokine, adhesion molecules, and improving the microvascular permeability.