中国血液净化

中国血液净化 ›› 2021, Vol. 20 ›› Issue (04): 258-262.doi: 10.3969/j.issn.1671-4091.2021.04.010

• 基础研究 • 上一篇    下一篇

Klotho 蛋白在缺血再灌注急性肾损伤中的动态变化

张菁菁1,曹新岭1,王顺1   

  1. 1新疆医科大学第一附属医院肾脏疾病中心肾脏一科
  • 收稿日期:2020-08-18 修回日期:2021-02-03 出版日期:2021-04-12 发布日期:2021-04-12
  • 通讯作者: 王顺 Wangshun128@126.com E-mail:yuqin2010723@163.com
  • 基金资助:
    新疆维吾尔自治区自然科学基金资助项目(2016D01C319)

Dynamic changes of Klotho protein in ischemia- reperfusion of acute kidney injury patients 

  1.  1Department of Nephrology, First Affiliated Hospital of Xinjiang Medical University; Kidney Disease Center, Xinjiang Uygur Autonomous Region, Xinjiang 830054, China
  • Received:2020-08-18 Revised:2021-02-03 Online:2021-04-12 Published:2021-04-12

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摘要： 【摘要】目的观察Klotho 蛋白在缺血再灌注急性肾损伤(acute kidney injury，AKI)中的动态变化。方法将120 只Wistar 雄性大鼠随机分为正常+生理盐水组(Norm+NS)、假手术+生理盐水组(Sham+NS)、假手术+Klotho 组(Sham+Klotho)、缺血再灌注手术+生理盐水组(I/R+NS)、手术+Klotho 组(I/R+Klotho)，建立缺血-再灌注AKI 模型，同时各组于造模成功1h、5h、12h、24h 分别处死大鼠6 只，分别测定血清尿素氮(blood urea nitrogen，BUN)和血肌酐(serum creatinine,Scr)，检测血清Klotho 蛋白水平，Klotho mRNA 表达情况；应用Pearson 直线相关法分析AKI 时大鼠肾组织以及血清的Klotho 蛋白与Scr 水平之间的关系。结果缺血再灌注24h 后，与Norm+NS 组、Sham+NS 组相比，I/R+NS 组Scr、BUN 以及肾小管损伤评分上升(tScr=3.767,4.145，tBUN=14.533，15.047，t 肾小管评分=153.093，7.261；P 值分别为0.013，0.009，＜0.001，＜0.001，＜0.001,0.008)，肾小管上皮细胞明显变性、坏死，而外源性给与Klotho 蛋白的I/R+Klotho 组Scr、BUN 和肾小管损伤评分较I/R+NS 组降低(t 值分别为10.220，9.571，11.076；P 值均＜0.001)，空泡变性减少；I/R+NS 组血清、肾组织Klotho 蛋白以及Klotho mRNA 的表达低于Norm+NS 组、Sham+NS 组。结论缺血再灌注急性肾损伤后小鼠血清及肾组织局部Klotho 蛋白表达均下调，Klotho 蛋白水平的下降可能与急性肾损害密切相关，Klotho 蛋白可能是AKI的保护性因素。

关键词: Klotho 蛋白, 缺血-再灌注肾损伤, 急性肾损伤

Abstract: 【Abstract】Objective To observe the dynamic changes of Klotho protein in acute kidney injury (AKI) during ischemia- reperfusion, and to further explore the role of Klotho protein in AKI. Methods A total of 120 Wistar male rats were randomly divided into Norm+NS group (normal rats + normal saline), Sham+NS group (sham operation + normal saline), Sham+Klotho group (sham operation +Klotho), I/R+NS group (ischemia-reperfusion + normal saline), and I/R+Klotho group (ischemia- reperfusion + Klotho) to establish the ischemia- reperfusion AKI groups and control groups. After the establishment of the models for 1h, 5h, 12h and 24h, six rats in each group were sacrificed. Blood urea nitrogen (BUN), serum creatinine (Scr), serum and kidney Klotho protein (ELISA method) and Klotho mRNA (RT-PCR method) were assayed. Pearson linear correlation method was used to analyze the relationship between serum and kidney Klotho protein levels and Scr level during AKI. Results After ischemia-reperfusion for 24h in I/R+NS group, Scr and BUN levels and renal tubular injury score increased as compared with those in Norm+NS group and Sham+ NS group (for Scr: t=3.767 and 4.145, P=0.013 and 0.009; for BUN: t=14.533 and 15.047, P<0.001; for renal tubular injury score: t=153.093 and 7.261, P<0.001 and t=0.008), and renal tubular epithelial cells showed significant degeneration and necrosis. In contrast in I/R+Klotho group in which exogenous Klotho protein was supplied, Scr and BUN levels and renal tubular injury score decreased (t=10.220, 9.571 and 11.076; P<0.001) and vacuolar degeneration of the renal tubular epithelial cells decreased, as compared with those in I/R+NS group. The content of Klotho protein and the expression of Klotho mRNA in sera and kidney tissues were lower in I/R+NS group than in Norm+NS group and Sham+NS group(P＜0.05). Conclusion In rats with ischemia-reperfusion AKI, Klotho protein and the expression of Klotho gene in serum and kidney decreased significantly. The decrease
of Klotho protein level is closely related to AKI. Klotho protein may be a protective factor for AKI.

Key words: Klotho protein, Ischemia-reperfusion renal injury, Acute kidney injury

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