Activation of sensory neurons reduces ischemia/ reperfusion-induced acute renal injury in rats

感觉神经元的激活可减轻大鼠缺血/再灌注引起的急性肾损伤

基本信息

批准号：
19592092
负责人：
NOGUCHI Takayuki
金额：
$ 2.91万
依托单位：
Oita University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2007
资助国家：
日本
起止时间：
2007 至 2009
项目状态：
已结题

项目摘要

PGI1 produced by endothelial cells improves ischemia/reperfusion-induced acute renal injury by inhibiting leukocyte activation in rat. However, the underlying mechanism of increased PGI2 production is not fully elucidated. Activation of sensory neurons increases endothelial PGI2 production byincreasing calcitonin gene-related peptide (CGRP) in rat hepatic ischemia or reperfusion. We examined here whether activation of sensory neurons increases PGI2 endothelial production, thereby reducing ischemia/reperfusion-induced acute renal injury. Renal tissue level of CGRP and 6-keto-PGF1α a stable metabolite of PGI2, increased after renal ischemia/reperfusion, peaking at 1h after reperfusion. Overexpression of CGRP was also noted at 1 h after reperfusion. Increases in renal tissue levels of 6-keto-PGF1α at 1h after reperfusion were significantly inhibited by pretreatment with capsazepin, CGRP(8-37), indomethacin. Pretreatment with capsazepin, CGRP (8-37), indomethacin, and denervation of primary sensory nerves significantly increased blood urea nitrogen and serum creatinine levels, renal vascular permiabilit6y, renal tissue levels of MPO activity, CINC, and TNF-α, and decreased renal tissue blood flow. However, pretreatment with CGRP significantly improved these changes. Our result suggests activation of sensory neurons in the pathologic process of ischemia/reperfusion-induced acute renal injury. Such activation reduces acute renal injury attenuating inflammatory responses through enhanced endothelial PGEI2 production.

内皮细胞产生的PGI1通过抑制大鼠的白细胞活化来改善缺血/再灌注诱导的急性肾损伤。但是，PGI2产生增加的潜在机制尚未完全阐明。感觉神经元的激活通过促进大鼠肝缺血或再灌注中降钙素基因相关肽（CGRP）来增加内皮PGI2的产生。我们在这里检查了感觉神经元的激活是否会增加PGI2内皮产生，从而减少缺血/再灌注诱导的急性肾损伤。 CGRP的肾脏组织水平和6-酮PGF1α稳定的PGI2代谢产物，肾脏缺血/再灌注后升高，再灌注后1H峰值。再灌注后1小时，CGRP的过表达也被发现。再灌注后1H时1H的6-酮PGF1α的肾脏组织水平的升高通过用辣椒粉，CGRP（8-37），吲哚美辛预处理来显着抑制。用辣椒粉，CGRP（8-37），吲哚美辛进行预处理以及原发感觉神经的去神经明显增加了血液尿素氮和血清肌酐水平，肾血管允许6Y，MPO活性的肾脏组织水平，CINC和TNF-α和TNF-α以及肾脏组织血液流量增加。但是，使用CGRP进行预处理可显着改善这些变化。我们的结果表明，在缺血/再灌注引起的急性肾损伤的病理过程中激活感觉神经元。这种激活通过增强的内皮PGEI2产生来减少急性肾脏损伤，从而减弱炎症反应。