小鼠脓毒症急性肾损伤模型制备及肾功能损伤指标评价  

A sepsis-inducedacute kidney injury mouse model and its kidney injury evaluation

作　　者：金魁[1] 刘宝[1] 邵敏[1] 周树生[1] 高晓兰[1] 

机构地区：[1]安徽医科大学附属省立医院危重病医学科,安徽合肥230001

出　　处：《中国急救医学》2015年第5期394-397,I0001,共5页Chinese Journal of Critical Care Medicine

基　　金：基金项目：国家临床重点专科建设基金（2011-1563）

摘　　要：目的：研究使用小鼠盲肠结扎穿刺（ CLP）模型，模拟脓毒症急性肾损伤（ AKI）病理生理过程，研究不同结扎长度（比率）对死亡率的影响，选取最为适宜的结扎长度，并观察结扎后肾损伤标志物及肾脏病理变化。方法实验共纳入81只小鼠分别进行：①生存率研究分为CLP组（以25％、50％结扎比率）及假手术组，观察7 d记录生存时间。②选取生存率较为适合的结扎比率，再次行CLP术后，检测肾脏损伤标志物血清肌酐（ Cr）、中性粒细胞酯酶（ NGAL）、胱抑素C （Cystatin C）及白细胞介素－6（IL－6）。③AKI发生后进行肾脏病理检查。结果 CLP模型盲肠结扎50％与25％24 h死亡率100％ vs 7％；结扎25％后，肾脏损伤标志物胱抑素C、中性粒细胞酯酶、血清肌酐于CLP术后2 h开始升高，胱抑素C于术后18 h达峰，中心粒细胞酯酶及肌酐于术后24 h达峰，IL－6于术后6 h达峰。病理检查提示，肾小管上皮细胞空泡形成明显增多，电镜检查提示空泡内含吞噬线粒体结构。结论 CLP模型可模拟脓毒症相关性肾损伤，其损伤达峰时间为造模后24 h。肾脏病理检查提示肾小管上皮空泡改变。Objective To examine the mortality and acute kidney injury in the cecum ligation and puncture （ CLP ） model with different ligation proportion.Methods Eighty -one mice were assigned to 3 different experiments.①Survival analysis between 25% vs 50% ligation of CLP model.②Analysis of 3 renal injury biomarkers （serum creatinine, NGAL, cystatin C） and cytokine of IL-6.③Renal histopathology at the most severely injured time point.Results The mortality rate of 50%ligation of CLP model at 48 hours was 100% whereas the 25% ligation mortality at 24 hours was 7%, and the 48 hours mortality was about 50%.Renal biomarkers of Creatinine, NGAL increased from 2 hours and reach their peak at 24 hours, by contrast, Cystatin C and IL-6 reach the highest level at 18 and 6 hours.Apical vacuolization can be found in the histopathology of kidneys at 24 hours after CLP but with absence of necrosis.Conclusion Cecum ligation （ 25%） and puncture through and through （2 holes） can mimic sepsis induced AKI, study of biomarkers of renal injury show kidney injury may most severely at 24 hours.

关 键 词：急性肾损伤(AKI) 盲肠结扎穿刺模型 脓毒症 生物学标志物 炎症因子 

分 类 号：R692[医药卫生—泌尿科学]