目的 研究乌司他丁预处理对失血性休克大鼠肺组织损伤的保护作用。方法 将雄性SD大鼠随机分为对照组、模型组和乌司他丁3、6万U/kg组，每组各8只。对照组、模型组通过尾静脉在20 min内微量泵注5 mL生理盐水，乌司他丁组尾iv 3、6万U/kg乌司他丁溶液5 mL。4 h后，按30 mL/kg经大鼠股动脉通道在10 min之内匀速抽取血液诱发失血性休克。维持休克状态60 min后，抽取的血液和乳酸林格氏液（30 mL/kg）在30 min内通过尾静脉匀速输注到大鼠体内复苏。在复苏后4 h测定大鼠肺组织超氧化物歧化酶（SOD）、丙二醛（MDA）；采用Western blotting法检测Bcl-2、Bax和caspase-3蛋白表达量；测量支气管肺泡灌洗液（BAL）中的蛋白质和白细胞（WBC）含量。进行肺组织学观察。结果 与模型组比较，6万U/kg乌司他丁预处理使肺组织SOD活性显著升高，MDA下降（P<0.05）。与模型组比较，6万U/kg乌司他丁预处理使肺组织Bcl-2表达显著上升，Bax和caspase-3表达显著减弱（P<0.05）。与模型组比较，6万U/kg乌司他丁预处理使肺组织BAL中蛋白、WBC含量显著减少（P<0.05）。结论 6万U/kg乌司他丁预处理对缺血再灌注大鼠肺损伤具有保护作用，其作用机制是改善肺组织的抗氧化作用。

Objective To study protective effects of ulinastatin pretreatment on lung tissue injury in hemorrhagic shock rats. Methods Male SD rats were randomly divided into control group, model group, and ulinastatin (30 000 and 60 000 U/kg) group, and each group had 8 rats. Rats in control group and model group were infused with 5 mL normal saline by tail vein in 20 min. Rats in ulinastatin groups were tail vein iv 5 mL ulinastatin solution 30 000 and 60 000 U/kg, respectively. After 4 h, 30 mL/kg of blood was extracted at a uniform rate through the femoral artery of the rats within 10 min to induce hemorrhagic shock. After the shock state was maintained for 60 min, the blood and Lactated Ringer's solution (30 mL/kg) were injected into the rats at a uniform rate through the tail vein for resuscitation within 30 min. After 4 h of recovery, SOD and MDA were determined, and the protein expressions of Bcl-2, Bax, and caspase-3 were determined by Western blotting method. Protein and WBC in BAL were measured, and the histopathological changes of lung were observed. Results Compared with the model group, ulinastatin pretreatment at 60 000 U/kg could significantly increase SOD activity and decreased MDA concentration in lung tissues (P<0.05). Compared with the model group, ulinastatin pretreatment at 60 000 U/kg could significantly increase the expression of Bcl-2 in lung tissues, and decreased the expression of Bax and caspase-3 (P<0.05). Compared with the model group, the protein and WBC content in lung tissues were significantly reduced by 60 000 U/kg ulinastatin pretreatment (P<0.05). Conclusion Ulinastatin pretreatment at 60 000 U/kg has a protective effect on lung injury in ischemia reperfusion rats, and the mechanism is to improve the antioxidant effect of lung tissue.

湖北省自然科学基金资助项目（2014CFB733）