摘要
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.
出处
《中华神经医学杂志》
CAS
CSCD
2008年第12期1234-1237,共4页
Chinese Journal of Neuromedicine
基金
广东省自然科学基金(06021323)