小鼠单侧肾缺血再灌注缺血时间与急性肾损伤发生的关系研究  

Relationship between acute kidney injury and ischemia time after unilateral renal ischemia reperfusion in mice

作　　者：陈健文[1,2] 王雷[1] 李怀康 焦启龙 袁清 黄燕 李修彬 徐俊楠 王晨峰 王保军[1] 马鑫[1] CHEN Jianwen;WANG Lei;LI Huaikang;JIAO Qilong;YUAN Qing;HUANG Yan;LI Xiubin;XU Junnan;WANG Chenfeng;WANG Baojun;MA Xin(Department of Urology,the First Medical Center,Chinese PLA General Hospital,Beijing 100853,China;Department of Nephrology,the First Medical Center,Chinese PLA General Hospital,Chinese PLA Institute of Nephrology,State Key Laboratory of Kidney Diseases,National Clinical Research Center for Kidney Diseases,Beijing Key Laboratory of Kidney Diseases,Beijing 100853,China)

机构地区：[1]解放军总医院第一医学中心泌尿外科,北京100853 [2]解放军总医院第一医学中心肾脏病科,解放军肾脏病研究所,肾脏疾病国家重点实验室,国家慢性肾病临床医学研究中心,肾脏疾病研究北京市重点实验室,北京100853

出　　处：《解放军医学院学报》2021年第12期1286-1292,共7页Academic Journal of Chinese PLA Medical School

基　　金：国家自然科学基金项目(81970665,82100713,81970594);中国博士后科学基金(2021T140791)。

摘　　要：背景在泌尿外科领域,针对局限性肾肿瘤施行肾部分切除术时需短暂夹闭肾动脉,造成肾缺血。多长的肾缺血时间不会导致急性肾损伤(acute kidney injury,AKI)是迫切需要明确的临床问题。目的探究缺血再灌注急性肾损伤模型中不同缺血时间对AKI发生的影响,为泌尿外科肾部分切除术缺血时间对AKI发生的影响提供基础研究证据。方法选取8周雄性C57小鼠15只,按照缺血不同时间(缺血0 min、15 min、25 min、30 min、45 min)分为5组,每组3只。在37℃~38℃恒温垫上维持体温恒定,行左侧肾缺血再灌注+右侧肾切除手术,记录每只小鼠手术时间、术前体质量、健侧切除右肾重量。术后密切观察小鼠一般状态,术后24 h记录体质量,采集血液检测血清肌酐、尿素氮,取左侧手术肾测量肾重量,肾组织行病理学PAS染色检查。结果各组手术均顺利,切开皮肤至取出健侧右肾用时、切开皮肤至左侧肾夹闭用时、术前体质量、右肾重量与术前体质量比值,5组间无统计学差异(P>0.05)。术后小鼠30 min、45 min组一般状态较差,其余三组一般状态良好。缺血30 min、45 min组的血清肌酐、尿素氮、肾小管病理损伤评分、体质量减轻值、缺血后肾重量增加值、缺血左肾与术后体质量比值均较缺血0 min、15 min、25 min组显著升高(P<0.05)。缺血30 min、45 min组术后病理PAS染色可见皮质肾小管上皮细胞脱落,皮髓交界处大量细胞管型堵塞肾小管。缺血30 min、45 min组术后24 h肌酐、尿素氮、肾小管病理损伤评分均显著高于缺血0 min、15 min、25 min组(P<0.05)。结论小鼠单侧肾缺血再灌注AKI模型存在较窄的诱发缺血时间窗口(临界点),在37℃~38℃温缺血情况下,单侧肾缺血再灌注损伤导致AKI的缺血时间临界点为25~30 min,小于25 min不导致AKI发生,超过30 min时AKI发生。Background In the field of urology,nephron sparing surgery for localized renal tumors requires temporary clipping of the renal artery,resulting in renal ischemia.However,the duration of renal ischemia that will not lead to acute renal injury(AKI)is an urgent clinical problem to be solved.Objective To explore the influence of different ischemia time on AKI in ischemia reperfusion injury(IRI)model,so as to provide evidence for the influence of ischemia time on kidney damage after nephron sparing surgery in urology.Methods Fifteen male C57 mice at 8 weeks were selected and divided into 5 groups with 3 mice in each group according to different ischemia duration(0 min,15 min,25 min,30 min and 45 min).The body temperature was kept constantly on the 37℃-38℃constant temperature pads,then the left kidney IR+right kidney resection was performed.The operation time,preoperative weight and weight of right kidney of each mouse were recorded.The general state of the mice was closely observed and recorded postoperatively.The weight of the mice was recorded at 24 h after the operation.After anesthesia,blood was collected to detect serum creatinine and urea nitrogen,the left kidney was taken to measure the kidney weight,and the renal tissue was further examined by PAS staining.Results The operation was successful.There was no statistically significance in the duration from skin incision to removal of the healthy right kidney,the duration from skin incision to clipping of the left kidney,preoperative weight,and the ratio of right kidney weight to preoperative weight among the 5 groups(P>0.05).After operation,the mice in 30 min and45 min groups were in poor state,and the other three groups were in good condition.The creatinine,urea nitrogen,acute tubule necrosis scores,weight loss,kidney weight gain after ischemia,and the ratio of left kidney ischemia to postoperative weight were significantly higher in 30 min and 45 min ischemia groups than those in 0 min,15 min and 25 min ischemia groups(P<0.05).After30 min ischemia and 45 min

关 键 词：小鼠 缺血再灌注 急性肾损伤 缺血时间 临界点 肾部分切除术 

分 类 号：R692.5[医药卫生—泌尿科学]