乌司他丁对小鼠不同程度肠缺血-再灌注损伤的作用

目的观察乌司他丁对小鼠轻、重度肠缺血再灌注（I／R）损伤的作用。方法建立缺血时间分别为90min和180min的小鼠轻度肠I／R损伤模型（模型1）和严重肠I／R损伤模型（模型2）。动物随机分为正常对照组、假手术组、模型1对照组和治疗组、模型2对照组和治疗组，共六组（n=10）。模型1和模型2治疗组小鼠均于缺血结束后再灌注前即刻尾静脉注射乌司他丁16IU／g，相应对照组于缺血结束再灌注前注射等体积的生理盐水，再灌注2h后于下腔静脉采血。观察小肠黏膜的大体损伤情况；采用Chiu氏评分法对小肠病理损伤程度进行评分；检测黏膜髓过氧化物酶（MPO）活性；采用ELISA法检测血清肿瘤坏死因子-d（TNF-α）和白介素-6（IL-6）水平。结果正常对照组和假手术组小鼠肠黏膜结构正常，其余各组小鼠均有明显肠黏膜损伤，并伴有黏膜MPO活性增加及血清TNF-α和IL-6水平升高。与相应对照组比较，模型1治疗组小鼠的肠黏膜损伤显著加重，Chiu氏评分显著升高（P〈0．01）；但模型2治疗组小鼠的小肠损伤明显减轻，Chiu氏评分显著降低（P〈0．01）。模型1和模型2治疗组小鼠的血清TNF-α、IL-6水平及MPO活性均明显低于其相应对照组，差异有统计学意义（P〈0．01）。结论乌司他丁治疗可减轻严重肠I／R损伤但加重轻度肠I／R损伤，这一作用可能与其抗炎作用有关。

Effects of ulinastatin on mild and severe intestinal ischemia-reperfusion injuries of mice

Objective To evaluate the effects of ulinastatin on mild and severe intestinal ischemia/reperfusion （I/R） injuries of mice. Methods Intestinal I/R injury models for ischemic time of 90 min （model 1） and 180 rain （model 2） were established. Adult male C57BL/6 mice were randomly divided into 6 groups （n =10 each）, i.e. the normal control group, sham operation group, model 1 control group, model 1 treated group, model 2 control group, and model 2 treated group. Mice of the model 1 treated group and model 2 treated group were injected i. v. with ulinastatin （16 IU/g） after the ischemia and before the reperfusion. Mice of the model 1 control group and model 2 control group were injected with the same volume of normal saline at the same period of time. The blood of inferior vena cava was collected after two hours of reperfusion. Injuries of small intestinal mucosa were observed and the degrees of pathological injury of small intestine were scored by the Chiu scoring. The activity of myeloperoxidase （MPO） was detected and serum TNF-α and IL-6 levels were determined by the ELISA. Results The structure of small intestinal mucosa of the normal control group and sham operation group was normal. The small intestinal mucosa of other groups was significantly injured and the activity of MPO and levels of serum TNF-α and IL-6 were increased. Compared to the model 1 control group, injuries of small intestinal mucosa of the model 1 treated group were significantly severer and Chiu scores were significantly higher（P〈0.01）. While compared to the model 2 control group, injuries of small intestinal mucosa of the model 2 treated group were significantly milder and Chiu scores were significantly lower （P〈0.01）. The activity of MPO and levels of serum TNF-α and IL-6 of the model 1 treated group and model 2 treated group were significantly lower than those of relevant control groups. The differences were statistically significant （P〈0. 01）. Conclusion Ulinastatin can relieve severe I/R injuries while aggravate mild I/R injuries. This may be relevant to its anti- inflammation effect.