乌司他丁对脓毒症大鼠脑组织肿瘤坏死因子-α和白细胞介素-6的影响

Effect of ulinastatin on tumor necrosis factor-α and interleukon-6 expression in the brain tissue of rats with sepsis

目的探讨乌司他丁（UTI）对脓毒症大鼠脑组织肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）的影响。方法将50只SD大鼠按随机数字表法分为对照组（n=5）、脓毒症组（n=15）、预处理组（n=15）及治疗组（n=15）。后三组利用盲肠结扎穿孔法（CLP）制作大鼠脓毒症模型，预处理组在CLP前2h经尾静脉注射UTI2．5万U／kg，治疗组在CLP后2h经尾静脉注射UTI5万U／kg。分别在CLP后3h、6h及12h行脑灌流后活杀大鼠，取大鼠右脑行病理光镜观察．左脑匀浆后以放射免疫法检测脑组织TNF-α和IL-6的水平。结果脓毒症组TNF-α、IL-6水平较对照组在6h和12h均有明显升高，差异有统计学意义（P〈0．05）；预处理组及治疗组TNF-α水平较脓毒症组在6h、12h有明显下降，IL-6水平在12h有明显下降，差异均有统计学意义（P〈0．05）；预处理组和治疗组各时间点比较差异均无统计学意义（P〉0．05）。结论脓毒症大鼠脑组织中TNF-α、IL-6水平显著升高可能是脓毒症脑病的重要发病机制之一；UTI可降低脓毒症大鼠脑组织中TNF-α、IL-6水平，减轻脑损伤，具有脑保护作用；预防给药（半治疗剂量）与治疗给药疗效相当。

Objective To investigate the effects of ulinastatin on the expressions of tumor necrosis factor-α（TNF-α） and interleukon-6 （IL-6） in the brain tissue of rats with sepsis. Methods Fifty SD rats were randomly divided into control （n=5）, sepsis （n=15）, ulinastatin pretreatment （n=15） and ulinastatin treatment （n=15） groups. Sepsis was induced in the latter 3 groups by cecal ligation and puncture （CLP）, and in the ulinastatin pretreatment and treatment groups, ulinastatin was administered at the dose 25 000 U/kg 2 h before the operation and at 50 000 U/kg 2 h after the operation, respectively. The rats were sacrificed at 3, 6 and 12 h after CLP, and the brain tissues from the left hemisphere was collected for measurement of TNF-α and IL-6 levels by radioimmunity, and those from the right hemisphere was used for pathological examination. Results Compared with control group, the rats in the sepsis group showed obviously increased TNF-α and IL-6 levels in the brain tissues 6 and 12 h after CLP （P〈0.05）. Ulinastatin treatment before and after the CLP both resulted in significant reduction in TNF-α levels 6 h after CLP in comparison with the levels in the sepsis group （P〈0.05）, and significant reduction of IL-6 levels occurred till 12 h after CLP （P〈0.05）. No significant differences in TNF-α and IL-6 levels were noted between ulinastatin pretreatment and treatment groups （P〉0.05）. Conclusion The inflammatory response caused by elevated TNF-α and IL-6 levels in the brain of septic rats may be an important mechanism of septic encephalopathy. Ulinastatin can reduce TNF-α and IL-6 levels in the brain of septic rats to alleviate sepsisnduced brain injuries, and its therapeutic and prophylactic （at half dose） administration produces similar effects.