
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
刘赟, 吴星恒
中国当代儿科杂志 ›› 2017, Vol. 19 ›› Issue (2) : 237-241.
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
Effect of ulinastatin on serum levels of tumor necrosis factor-α, P-selectin, and thrombin-antithrombin complex in young rats with sepsis
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。
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, shamoperation 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.
乌司他丁 / 脓毒症 / 肿瘤坏死因子-α / P-选择素 / 凝血酶抗凝血酶复合物 / 大鼠
Ulinastatin / Sepsis / Tumor necrosis factor-α / P-selectin / Thrombin-antithrombin complex / Rats
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