乌司他丁对内毒素致小鼠脑损伤的影响

Effect of ulinastatin on brain injury induced by lipopolysaccharide in mice

目的 评价乌司他丁对内毒素（LPS）致小鼠脑损伤的影响.方法 成年雄性C57小鼠90只,3-4月龄,体重200 - 300 g,采用随机数字表法分为3组（n=30）：对照组（C组）、LPS组和乌司他丁组（U组）.U组腹腔注射乌司他丁10 000 U/kg,L组腹腔注射等容量生理盐水,10 min后,脑室内注射LPS 1 μg/g制备小鼠脑损伤模型.分别于LPS注射后1、3和7d时,取10只小鼠,取尾动脉血样,采用ELISA法测定血浆S100β蛋白和神经元特异性烯醇化酶（NSE）的浓度;然后处死小鼠,取海马组织,测定IL-1β和TNF-α的含量及其mRNA的表达水平.结果 与C组比较,LPS组和U组LPS注射后1、3和7d时血浆S100β蛋白和NSE的浓度、海马组织TNF-α和IL-1β的含量升高,LPS注射后1和3d时海马组织IL-1β和TNF-α的mRNA表达上调（P＜0.01）;与LPS组比较,U组LPS注射后1和3d时血浆S100β蛋白和NSE的浓度、海马组织TNF-α和IL-1β的含量降低,海马组织IL-1β和TNF-α的mRNA表达下调（P＜0.01）.结论 乌司他丁可减轻LPS致小鼠脑损伤,其机制与抑制炎性反应有关.

Objective To evaluate the effect of ulinastatin on brain injury induced by lipopolysaccharide （LPS） in mice.Methods Ninety adult male C57 mice,aged 3-4 months,weighing 200-300 g,were randomly divided into 3 groups （n =30 each） using a random number table：control group （C group）,LPS group and ulinastatin group （U group）.Group U received intraperitoneal injection of ulinastatin 10 000 U/kg,while group L received the equal volume of normal saline,and 10 min later brain injury was produced with LPS 1 μg/g injected into the cerebral ventricle.Ten animals were chosen and blood samples were taken for determination of plasma concentrations of S100β protein and neuron-specific enolase （NSE） at 1,3 and 7 days after LPS injection.Then the animals were sacrificed and hippocampal tissues were obtained for determination of interleukin-1β （IL-1 β） and tumor necrosis factor-α （TNF-α） contents and IL-1β mRNA and TNF-α mRNA expression.Results Compared with C group,the plasma concentrations of S100β protein and NSE and contents of IL-1β and TNF-α were significantly increased at 1,3 and 7 days after LPS injection,and IL-1β mRNA and TNF-α mRNA expression was up-regulated at 1 and 3 days after LPS injection in LPS and U groups.Compared with group LPS,the plasma concentrations of S100β protein and NSE and contents of IL-1β and TNF-α were significantly increased,and IL-1β mRNA and TNF-α mRNA expression was down-regulated at 1 and 3 days after LPS injection in group U.Conclusion Ulinastatin can attenuate brain injury induced by LPS in mice,and the mechanism is related to inhibited inflammatory responses.