缺血预适应对大鼠保留肾单位手术中缺血再灌注损伤的保护作用及其机制研究  

Protective effects and mechanism of ischemic preconditioning in ischemia-reperfusion injury after nephron sparing surgery in rats

作　　者：刘敬宇 辛慧[1] 周昌成 吴然[1] 贾瑞鹏[1] Liu Jingyu;Xin Hui;Zhou Changcheng;Wu Ran;Jia Ruipeng(Department of Urology,Nanjing Hospital Affiliated to Nanjing Medical University(Nanjing First Hospital),Nanjing 210006,China)

机构地区：[1]南京医科大学附属南京医院(南京市第一医院)泌尿外科,南京210006

出　　处：《中华解剖与临床杂志》2020年第5期548-554,共7页Chinese Journal of Anatomy and Clinics

基　　金：国家自然科学基金资助项目(81570613、81070597);江苏省社会发展项目(BE2017615)。

摘　　要：目的探讨缺血预适应(IPC)动员肾祖细胞(RPC)归巢在保留肾单位手术(NSS)中对肾脏缺血再灌注损伤(IRI)的保护作用及其发生机制。方法选取2~3月龄、体质量250~300 g的雄性SD大鼠54只,建立切除右肾的单肾模型后采用数字表法随机分为3组,每组18只:假手术组(Sham组,无血管夹闭),NSS组(肾动脉夹闭45 min后行NSS),IPC组(先进行肾动脉夹闭15 min,再灌注10 min预处理,再行NSS)。分别在术后12、24、72 h每组各取出6只大鼠,收集血液及肾组织标本,之后采用颈椎脱臼法处死大鼠。观察项目:(1)检测血肌酐(SCr)、尿素氮(BUN);(2)组织病理学检查及肾小管损伤评分;(3)在24 h观察IPC对肾组织中RPC数量的影响,以及IPC对基质细胞衍生因子(SDF-1)、受体CXCR7表达水平的影响。结果(1)术后12、24、72 h时3组大鼠SCr和BUN值比较,IPC组分别为(65.0±10.78)、(91.5±15.12)、(52.6±11.68)μmol/L和(14.78±2.77)、(18.31±4.99)、(9.41±2.73)mmol/L,NSS组分别为(80.5±12.63)、(116.9±14.32)、(83.7±11.43)μmol/L和(18.58±4.18)、(28.86±5.64)、(19.49±3.83)mmol/L,Sham组分别为(41.5±7.36)、(39.7±7.55)、(42.7±7.15)μmol/L和(7.72±1.75)、(7.40±1.98)、(6.83±2.09)mmol/L;除72 h时IPC组与Sham组SCr和BUN值比较差异无统计学意义(P>0.05)外,在12 h和24 h,IPC组均高于Sham组、低于NSS组,差异均有统计学意义(P值均<0.05)。(2)术后12、24、72 h肾小管损伤评分IPC组和NSS组均高于Sham组,术后12、24 h IPC组较NSS组肾小管损伤评分低,差异均有统计学意义(P值均<0.05)。(3)术后24 h,IPC组和NSS组大鼠肾组织中RPC数量明显增加、SDF-1和CXCR7表达显著升高,差异均有统计学意义(P值均<0.05)。结论IPC可促进RPC归巢,缓解NSS中IRI损伤程度,保护肾功能,SDF-1/CXCR7轴可能在这一动员过程中发挥了重要作用。Objective This study aimed to investigate the protective effects and underlying mechanism of ischemic preconditioning(IPC)-induced renal progenitor cell(RPC)homing to renal ischemia-reperfusion injury(IRI)in nephron sparing surgery(NSS).Methods Fifty-four male Sprague-Dawley rats aged 2-3 months and weighing 250-300 g were selected.The rats were randomly divided into three groups with a random number table following right-side nephrectomy.Eighteen rats were included in the three groups,namely,sham operation group(Sham group,surgery without vascular clamping),simple NSS group(NSS group,renal artery clamping for 45 min with NSS),and ischemic preconditioning+NSS group(IPC group,pretreated with 15 min ischemia and 10 min reperfusion before NSS).Six rats were taken from each of the three groups,blood and kidney tissue samples were collected at 12,24,and 72 h after surgery.The rats were then sacrificed through cervical dislocation.The observation items were as follows:(1)Detection of serum creatinine(SCr)and blood urea nitrogen(BUN);(2)Histopathological examination and renal tubular injury score;(3)The effects of IPC on RPCs and the effects of stromal cell-derived factor(SDF-1)and receptor CXC chemokine receptor type 7(CXCR7)expression levels.Results(1)The SCr and BUN of the IPC[(65.0±10.78),(91.5±15.12),(52.6±11.68)μmol/L and(14.78±2.77),(18.31±4.99),(9.41±2.73)mmol/L]and the NSS groups[(80.5±12.63),(116.9±14.32),(83.7±11.43)μmol/L and(18.58±4.18),(28.86±5.64),(19.49±3.83)mmol/L]were higher than in the Sham group[(41.5±7.36),(39.7±7.55),(42.7±7.15)μmol/L and(7.72±1.75),(7.40±1.98),(6.83±2.09)mmol/L]at 12,24,and 72 h after surgery,and the IPC group was lower than the NSS group.Although no statistically significant difference was found between the IPC and Sham groups at 72 h after surgery(P>0.05),the difference was statistically significant(all P values<0.05).(2)At 12,24,and 72 h after surgery,the renal tubular injury scores in the IPC and NSS groups were higher than those in the Sham group,and the

关 键 词：再灌注损伤 缺血预适应 肾祖细胞 保留肾单位手术 基质细胞衍生因子-1 细胞表面趋化因子受体7 大鼠 

分 类 号：R699[医药卫生—泌尿科学] R-332[医药卫生—外科学]