通过短时间预缺血改变肾小管上皮细胞命运诱导肾脏缺血耐受

中华肾脏病杂志 ›› 2011, Vol. 27 ›› Issue (3) : 198-202.

基础研究

蒋素华邹建洲刘红任丽许迅辉陈越丁小强

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Tilting the balance of tubular cell fate toward survival contributes to ischemic tolerance in kidney

JIANG Su-hua, ZOU Jian-zhou, LIU Hong, REN Li, XU Xun-hui, CHEN Yue, DING Xiao-qiang

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摘要

目的探讨短时间缺血预处理在诱导肾脏缺血耐受中的作用，及其对肾小管上皮细胞坏死、凋亡、增殖等的影响。方法雄性SD大鼠随机分为3组：假手术组（Sham），只分离两侧肾蒂，不进行夹闭；单纯缺血再灌注组（I/R），第0天假手术，第4天用无损伤动脉夹夹闭两侧肾蒂40 min，然后恢复灌注；缺血预适应组（IPC），第0天预缺血20 min，第4天再次缺血40 min。PAS染色观察肾组织形态学，透射电镜观察小管上皮细胞超微结构，原位末端标记法（TUNEL）检测细胞凋亡情况，免疫组织化学法观察肾小管上皮细胞增殖核抗原（PCNA）的表达。结果　与单纯缺血再灌注组相比，缺血预适应组肾脏功能和病理性损伤显著减轻（P < 0.01）；大鼠死亡率从33%降低为0 ；肾小管上皮细胞凋亡和坏死显著减少（P < 0.05），细胞增殖（PCNA阳性）显著增多（P < 0.01）。结论短时间缺血预处理能诱导肾脏耐受长时间缺血，减少小管上皮细胞死亡和促进其及时增殖修复可能是预缺血发挥肾脏保护作用的机制之一。

Abstract

Objective To explore the role of brief ischemia pretreatment in the induction of renal ischemic tolerance, and investigate its effects on tubular cell necrosis, apoptosis and proliferation. Methods Male Sprague-Dawley rats were randomly divided into three groups, including sham-operated group (Sham), ischemia/reperfusion injured group subjected to the occlusion of both renal pedicles for 40 min followed by reperfusion (I/R), and preconditioned group with 20-min ischemia pretreatment induced 4 days before I/R (IPC). Histological changes were evaluated by PAS staining. The ultra-structure of tubular cells was observed by transmission electron microscopy (TEM). Apoptosis was confirmed by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labeling (TUNEL). The proliferation of tubular cells was evaluated with proliferating cell nuclear antigen (PCNA). Results Twenty-minites ischemia pretreatment offered both promising functional and histological protection against 40-min ischemia/reperfusion injury (P< 0.01). The mortality rate was reduced from 33% in I/R group to 0 in IPC group. The renoprotection offered by 20-min ischemia pretreatment was accompanied with reduced postischemic tubular cell apoptosis and necrosis (P<0.05), and increased cell proliferation (PCNA positive) (P< 0.01). Conclusions Brief and sublethal prior ischemia can render the kidney more tolerant to subsequent prolonged I/R injury. Its ability to tilt the balance of tubular cell fate toward survival, reducing postischemic cell death and enhancing cell proliferation, may play an important role in renal protection of ischemic preconditioning.

导出引用

蒋素华邹建洲刘红任丽许迅辉陈越丁小强. 通过短时间预缺血改变肾小管上皮细胞命运诱导肾脏缺血耐受[J]. 中华肾脏病杂志, 2011, 27(3): 198-202.

JIANG Su-hua;ZOU Jian-zhou;LIU Hong;REN Li;XU Xun-hui;CHEN Yue;DING Xiao-qiang. Tilting the balance of tubular cell fate toward survival contributes to ischemic tolerance in kidney[J]. Chinese Journal of Nephrology, 2011, 27(3): 198-202.

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Received	Revised	Published
1900-01-01	1900-01-01	2011-03-15
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2011-03-15

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