乌司他丁干预对脓毒症幼鼠血清肿瘤坏死因子-α、P-选择素和凝血酶抗凝血酶复合物水平的影响

目的探讨使用乌司他丁(UTI)作为早期干预药物对脓毒症幼鼠血清肿瘤坏死因子-α(TNF-α)、P-选择素、凝血酶抗凝血酶复合物(TAT)水平的影响及意义。方法将120只4周龄雄性大鼠随机分为正常对照组、假手术组、脓毒症组、低剂量UTI干预组(50 000 U/kg)和高剂量UTI干预组(200 000 U/kg),每组24只。采用改良的盲肠结扎穿孔法制作脓毒症大鼠模型,低剂量和高剂量UTI干预组在建模后分别尾静脉注射UTI。ELISA法测定6、12、24 h时各组大鼠血清TNF-α、P-选择素、TAT水平。结果脓毒症组大鼠血清TNF-α、TAT、P-选择素水平在6 h时即出现显著升高,血清TNF-α、TAT水平至24 h时仍呈持续升高状态(P0.05);P-选择素在12 h时达到峰值,24 h时出现回落(P0.05)。UTI干预组中,P-选择素和TAT水平变化趋势和脓毒症组相同,TNF-α水平在6 h出现明显的增高,但随时间延长逐渐降低,且变化幅度均显著小于脓毒症组(P0.05);高剂量组变化幅度显著小于低剂量组(P0.05)。结论 UTI早期干预对脓毒症幼鼠模型的凝血功能有明显的改善,能抑制TNF-α、P-选择素、TAT的生成,且高剂量组较低剂量组作用更显著。

Effect of ulinastatin on serum levels of tumor necrosis factor-α, P-selectin, and thrombin-antithrombin complex in young rats with sepsis

ObjectiveTo investigate the effect of ulinastatin (UTI) for early drug intervention on the serum levels of tumor necrosis factor-α (TNF-α), P-selectin, and thrombin-antithrombin complex (TAT) in young rats with sepsis.MethodsA total of 120 male rats aged 4 weeks were randomly divided into normal control group, sham-operation group, sepsis group, low-dose UTI group (50 000 U/kg), and high-dose UTI group (200 000 U/kg), with 24 rats in each group. Modified cecal ligation and puncture was performed to establish a rat model of sepsis, and the rats in the low- and high-dose UTI groups were given caudal vein injection of UTI after model establishment. ELISA was used to measure the serum levels of TNF-α, P-selectin, and TAT at 6, 12, and 24 hours after model establishment.ResultsThe sepsis group had significant increases in the serum levels of TNF-α, P-selectin, and TAT at 6 hours, and the serum levels of TNF-α and TAT continued to increase by 24 hours (P<0.05); P-selectin reached the peak at 12 hours and decreased slightly at 24 hours (P<0.05). The UTI groups had similar change patterns in the levels of P-selectin and TAT as the sepsis group. The UTI groups had significant increases in the level of TNF-α at 6 hours, but gradually decreased over time. The changes in serum levels of TNF-α, P-selectin, and TAT in the UTI groups were significantly smaller than in the sepsis group (P<0.05). The high-dose UTI group had signiifcantly smaller changes in serum levels of TNF-α, P-selectin, and TAT than the low-dose UTI group (P<0.05). ConclusionsEarly intervention with UTI can signiifcantly improve coagulation function and inhibit the production of TNF-α, P-selectin, and TAT in young rats with sepsis. High-dose UTI has a signiifcantly greater effect than low-dose UTI.