ARNT基因失活小鼠的肾脏缺血再灌注损伤

背景：如何有效防治肾脏的缺血再灌注损伤,一直是肾移植领域的研究重点。但目前其机制仍然不是很清楚。 目的：探讨缺氧诱导因子系统对小鼠肾缺血再灌注损伤的影响及可能的作用机制。 方法：选取两种小鼠,一种为芳香族碳氢化合物核转移子(aryl hydrocarbon receptor nuclear translocator,ARNT)基因敲除小鼠,一种为同窝对照组小鼠。每种小鼠分别进行假手术、缺血再灌注、缺血再灌注时注射重组人促红细胞生成素、缺血再灌注时注射等量生理盐水。建立小鼠肾脏缺血再灌注损伤模型,分别比较再灌注损伤后1 h血清促红细胞生成素含量、24 h血清肌酐值、肾组织PAS染色肾小管损伤评分和TUNEL法计算肾小管细胞凋亡数。 结果与结论：再灌注后1 h血清促红细胞生成素水平ARNT敲除组明显低于对照组(P < 0.01)。24 h血清肌酐水平ARNT敲除组明显高于对照组(P  < 0.01)。ARNT敲除组明显比对照组损伤程度重,肾小管评分明显高于对照组(P  < 0.01)。ARNT敲除组阳性凋亡细胞数明显多于ARNT+/+组(P < 0.01)。补充促红细胞生成素后,ARNT敲除组与对照组比较,差异无显著性意义(P  > 0.05)。结果表明,缺氧诱导因子系统对肾脏缺血再灌注损伤有重要的保护作用。可能是促红细胞生成素来介导其最大的保护效应。

Effects of inactivation of aryl hydrocarbon receptor nuclear translocator on renal ischemia reperfusion injury in mice

BACKGROUND:It is a hot investigation to many scholars that how to cure and prevent renal ischemic reperfusion injury (IRI) in a utility way, but the mechanism is unclear at present．The investigation indicates that hypoxia inducible factor (HIF) plays an important role during this process. OBJECTIVE:To investigate the effects and possible mechanism of HIFs on renal ischemia reperfusion injury in mice. METHODS:Two kinds of mice were selected: one kind was aryl hydrocarbon receptor nuclear translocator (ARNT) gene inactivation, and the other kind was used as controls. Each kind of mice were randomly divided into sham operation group, ischemic reperfusion group, ischemic reperfusion+ recombinant human erythropoietin (rhEPO) group, ischemic reperfusion+0.9% normal saline (NS) group. Mice were established for renal IRI models. Serum erythropoietin (EPO) levels after 1 hour and 24-hour serum creatinine (Cr) values were examined, 24-hour renal tubular injury score following PAS staining was recorded, and 24-hour renal tubular cell apoptosis was counted by using TUNEL method. RESULTS AND CONCLUSION:One hour after reperfusion ARNT knockout serum EPO levels were significantly lower than the control group (P < 0.01). At 24 hours, Cr levels of ARNT knockout mice were significantly higher than the control group (P < 0.01). Renal Tubular injury scores of ARNT knockout group were significantly higher than the control group (P< 0.01). The number of TUNEL positive cells of ARNT knockout group was significantly more than the control group (P < 0.01). After rhEPO injection, there were no significant difference between ARNT knockout mice and control mice (P > 0.05). The results showed that HIF system on renal ischemia reperfusion injury has important protective role. It may be the maximum protective effect mediated by EPO.