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陈健文, 王雷, 李怀康, 焦启龙, 袁清, 黄燕, 李修彬, 徐俊楠, 王晨峰, 王保军, 马鑫. 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[J]. 解放军医学院学报, 2021, 42(12): 1286-1292. DOI: 10.3969/j.issn.2095-5227.2021.12.011
引用本文: 陈健文, 王雷, 李怀康, 焦启龙, 袁清, 黄燕, 李修彬, 徐俊楠, 王晨峰, 王保军, 马鑫. 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[J]. 解放军医学院学报, 2021, 42(12): 1286-1292. DOI: 10.3969/j.issn.2095-5227.2021.12.011
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CHEN Jianwen, WANG Lei, LI Huaikang, JIAO Qilong, YUAN Qing, HUANG Yan, LI Xiubin, XU Junnan, WANG Chenfeng, WANG Baojun, MA Xin. Relationship between acute kidney injury and ischemia time after unilateral renal ischemia reperfusion in mice[J]. ACADEMIC JOURNAL OF CHINESE PLA MEDICAL SCHOOL, 2021, 42(12): 1286-1292. DOI: 10.3969/j.issn.2095-5227.2021.12.011
Citation: CHEN Jianwen, WANG Lei, LI Huaikang, JIAO Qilong, YUAN Qing, HUANG Yan, LI Xiubin, XU Junnan, WANG Chenfeng, WANG Baojun, MA Xin. Relationship between acute kidney injury and ischemia time after unilateral renal ischemia reperfusion in mice[J]. ACADEMIC JOURNAL OF CHINESE PLA MEDICAL SCHOOL, 2021, 42(12): 1286-1292. DOI: 10.3969/j.issn.2095-5227.2021.12.011
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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

    摘要
  • 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。

     

    Abstract:
      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 and 45 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). After 30 min ischemia and 45 min ischemia, pathological PAS staining showed cortical renal tubule epithelial cells abscission and a large number of cells blocking renal tubules at the cortical medulla junction (P<0.05), and the postoperative creatinine (24 h), urea nitrogen, renal tubular pathological injury scores were significantly higher than those of the 0 min, 15 min, 25 min groups (P<0.05).
      Conclusion  The mouse unilateral renal ischemia-reperfusion AKI model has a narrow ischemia time window (critical point of ischemia) for inducing AKI. Under the condition of 37℃-38℃ warm ischemia, the critical point of ischemia time for unilateral renal IRI to lead to AKI is between 25-30 min. When it is less than 25 min, AKI does not occur, but it occurs when it is more than 30 min.

     

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