Objective: To 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.
Methods: A 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.
Results: The 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 significantly smaller changes in serum levels of TNF-α, P-selectin, and TAT than the low-dose UTI group (P<0.05).
Conclusions: Early intervention with UTI can significantly improve coagulation function and inhibit the production of TNF-α, P-selectin, and TAT in young rats with sepsis. High-dose UTI has a significantly greater effect than low-dose UTI.
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（50000U/kg）和高剂量UTI干预组（200000U/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、24h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6h时即出现显著升高，血清TNF-α、TAT水平至24h时仍呈持续升高状态（P < 0.05）；P-选择素在12h时达到峰值，24h时出现回落（P < 0.05）。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6h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（P < 0.05）；高剂量组变化幅度显著小于低剂量组（P < 0.05）。
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。