乌司他丁对侵袭性念珠菌感染小鼠肝脏的保护作用及机制研究  

Hepatoprotective effect of Ulinastatin against invasive Candida infection in mouse and its mechanism

作　　者：李小悦[1] 黄顺伟[2] 江智毅[2] 沈利汉[1] 蔡立华[1] 

机构地区：[1]东莞市人民医院ICU,广东东莞523059 [2]中山大学附属第一医院SICU

出　　处：《中国急救医学》2013年第10期942-944,I0003,共4页Chinese Journal of Critical Care Medicine

基　　金：广东省医学科研基金项目（A2010150）;天普研究基金项目（01200909）;中山大学学生业余科研基金项目（2010045）

摘　　要：目的 探讨乌司他丁对侵袭性念珠菌感染小鼠肝脏的保护作用和可能机制.方法 雄性昆明小鼠60只,经CTX预处理后腹腔注射白色念珠菌混悬液,制作侵袭性念珠菌感染小鼠模型,随机分成对照组（n=20）、乌司他丁低剂量组（n=20）和乌司他丁高剂量组（n=20）.对照组给予抗真菌药物治疗,低剂量组给予抗真菌药物联合乌司他丁1×104 U/kg治疗,高剂量组给予抗真菌药物联合乌司他丁5×104 U/kg治疗,观察三组7天生存率、血胆红素、肝酶学和肝脏病理.结果侵袭性念珠菌感染小鼠模型制作成功.高剂量组7天生存率显著高于对照组（70%vs 30%,P=0.011）.低剂量组和高剂量组第7天肝组织白细胞介素-10（IL-10）均显著低于对照组（P〈0.05）.高剂量组小鼠第7天总胆红素、谷草转氨酶、谷丙转氨酶均显著低于对照组和低剂量组（P〈0.05）.低剂量组小鼠第7天总胆红素、谷草转氨酶、谷丙转氨酶与对照组之间差异无统计学意义（P〉0.05）.光镜下第7天高剂量组小鼠肝脏肝窦充血较对照组减轻,电镜下第7天高剂量组小鼠肝脏线粒体完整性优于对照组.结论 高剂量乌司他丁可以改善侵袭性念珠菌感染小鼠7天生存率,并减轻侵袭性念珠菌感染所致肝损伤,可能与保持肝脏线粒体的完整性有关.Objective To investigate the hepatoprotective effect of ulinastatin （UTI） against invasive Candida infection （ICI） in mouse and its mechanism. Methods Sixty Kunming mice were randomly assigned to control group, low- dose group and high- dose group （each n = 20）. Mouse ICI model was reproduced by intraperitoneal injection of White monilial suspension after CTX pretreatment. Mice in control group were treated with antifungal agents. Mice in low - dose group and high - dose group were treated with UTI 1×10^4 U/kg or 5 ×10^4 U/kg and antifungal agents. Survival rate, bilirubin, liver enzyme, histologic and electron microscopical observations were compared among these groups. Results There was significant difference in survival rate between control group （30%） and high - dose group （ 70% ） （ P = 0.011 ）. There were significant differences in IL - 10 among three groups （ P 〈 0. 05 ）. Bilirubin, glutamic oxalacetic transaminase, glutamic pyruvic transaminase in high - dose group were significantly lower than those in control group and low - dose group （ P 〈 0. 05 ）. There was no significant difference in bilirubin, glutamic oxalacetic transaminase, glutamic pyruvic transaminase between control group and low - dose group （ P 〉 0.05 ）. Congestion of hepatic sinus in high- dose group on day 7 was better than that in control group under the light microscope. Mitochondrial integrity in high - dose group on day 7 was better than that in control group under the electron microscope. Conclusion High - dose UTI could improve survival rate in mice with ICI through alleviating liver injury. The possible mechanism is maintaining mitochondrial integrity in liver.

关 键 词：侵袭性念珠菌感染 乌司他丁 肝损伤 生存率 

分 类 号：R519.3[医药卫生—内科学]