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术前免疫抑制治疗对健康大鼠缺血再灌注(I/R)损伤的影响。

The effects of preoperative immunosuppressive therapy on ischemia and reperfusion (I/R) injury in healthy rats.

作者信息

Kilinc Selcuk, Tan Sedat, Kolatan Efsun Hatice, Ruscuklu Dane, Satici Esra, Kemiksiz Mehmet, Dalkilic Lutfi, Erdogdu Umut Eren, Karaca Cezmi

机构信息

İzmir Tepecik Training and Research Hospital Transplant Department, Izmir, Turkey.

出版信息

Int Urol Nephrol. 2014 Feb;46(2):389-93. doi: 10.1007/s11255-013-0548-2. Epub 2013 Sep 8.

Abstract

PURPOSE

Warm-ischemia-induced injuries might be encountered during renal transplants from cadavers and healthy donors. Toll-like receptors (TLR) in ischemia-reperfusion (I/R) injury are one of the indicators of intracellular injury pathways. The intensity of ischemic injury is directly proportionate to high TLR levels. To minimize the I/R injury, we investigated TLR2 and TLR4 levels on rats, which were pretreated with tacrolimus (FK506) before I/R.

METHODS

Eight Wistar albino rats in the study group were administered .01 mg/kg intramuscular tacrolimus. Administration to the study group was performed 24 and 1 h before warm ischemia. Eight rats in the control group were injected with 0.1 c.c. of distilled water. Blood samples were collected from the tail veins of all the rats on the first, second and third days. Expression levels of TLR2 and TLR4 genes were analyzed using the polymerase chain reaction method, to determine any significant difference between the control and study groups on the days when blood was taken.

RESULTS

TLR2 (p = 0.045) and TLR4 (p = 0.022) levels in the study group were found to be statistically, and significantly, lower than those in the control group, on the second day following warm-ischemia- and reperfusion-induced injury.

CONCLUSIONS

Administration of immunosuppressive drugs to healthy donor rats led to a statistically significant reduction in the expression levels of TLR2 and TLR4 in the early period. In light of the data obtained by this study, we hypothesize that a preoperative therapy on donors might have a role in preventing I/R injury.

摘要

目的

在尸体供肾和健康供肾的肾移植过程中可能会出现热缺血诱导的损伤。缺血再灌注(I/R)损伤中的Toll样受体(TLR)是细胞内损伤途径的指标之一。缺血损伤的强度与高TLR水平直接成正比。为了将I/R损伤降至最低,我们研究了在I/R之前用他克莫司(FK506)预处理的大鼠的TLR2和TLR4水平。

方法

研究组的8只Wistar白化大鼠肌肉注射0.01mg/kg他克莫司。在热缺血前24小时和1小时对研究组进行给药。对照组的8只大鼠注射0.1cc蒸馏水。在第1、2和3天从所有大鼠的尾静脉采集血样。使用聚合酶链反应方法分析TLR2和TLR4基因的表达水平,以确定在采血日对照组和研究组之间是否存在任何显著差异。

结果

在热缺血和再灌注诱导损伤后的第二天,研究组的TLR2(p = 0.045)和TLR4(p = 0.022)水平在统计学上显著低于对照组。

结论

对健康供体大鼠给予免疫抑制药物导致早期TLR2和TLR4的表达水平在统计学上显著降低。根据本研究获得的数据,我们推测对供体进行术前治疗可能在预防I/R损伤中起作用。

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