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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PGI 1通过抑制白细胞活化改善大鼠缺血再灌注急性肾损伤然而，PGI 2产生增加的潜在机制尚未完全阐明。感觉神经元激活通过增加降钙素基因相关肽（CGRP）增加大鼠肝缺血再灌注时内皮细胞PGI_2的产生。我们在这里检查是否感觉神经元的激活增加PGI 2内皮细胞的生产，从而减少缺血/再灌注诱导的急性肾损伤。肾缺血再灌注后，肾组织CGRP和PGI 2的稳定代谢产物6-keto-PGF 1 α水平升高，再灌注后1h达高峰。再灌注后1h，CGRP表达明显增强。辣椒素、CGRP（8-37）、吲哚美辛预处理可明显抑制再灌注后1h肾组织6-keto-PGF_（1 α）水平的升高。给予辣椒西平、CGRP（8-37）、吲哚美辛和去神经支配可显著增加血尿素氮、血肌酐水平、肾血管通透性、肾组织MPO活性、CINC和TNF-α水平，减少肾组织血流量。然而，CGRP预处理显著改善了这些变化。我们的研究结果表明，在缺血/再灌注诱导的急性肾损伤的病理过程中，感觉神经元的激活。这种激活通过增强内皮PGEI 2的产生来减少急性肾损伤，减弱炎症反应。