Activation of Sensory Neurons Reduces Ischemia/Reperfusion-induced Acute Renal Injury in Rats
Activation of Sensory Neurons Reduces Ischemia/Reperfusion-induced Acute Renal Injury in Rats
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DOI：
10.1097/aln.0b013e3181942f3c
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发表时间：
2009-02-01
期刊：
影响因子：
8.8
通讯作者：
Noguchi, Takayuki
中科院分区：
文献类型：
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作者：
Mizutani, Akio;Okajima, Kenji;Noguchi, Takayuki
背景资料：内皮细胞产生的前列腺素I（2）（PGI（2））通过抑制白细胞活化改善大鼠缺血/再灌注诱导的急性肾损伤。然而，PGI增加的潜在机制（2），生产还不完全清楚。感觉神经元激活通过释放降钙素基因相关肽（CGRP）增加肝缺血或再灌注大鼠内皮细胞PGI（2）的产生。我们在此研究感觉神经元的激活是否增加PGI（2）内皮的产生，从而减少缺血/再灌注诱导的急性肾损伤。结果：肾缺血再灌注后，大鼠肾组织中CGRP和6-keto-PGF（1 α）（PGI（2）的稳定代谢产物）的含量增加。再灌注1h达高峰。再灌注后1h，CGRP表达明显增强。再灌注后1 h肾组织6-酮-前列腺素F（1 α）水平的增加被辣椒平预处理显著抑制。CGRP（8 - 37））。和吲哚美辛。辣椒平预处理。CGRP（8 - 37）。吲哚美辛和初级感觉神经的去神经支配显著增加了血尿素氮和血清肌酐水平、肾血管通透性、肾组织水平（髓过氧化物酶活性、嘌呤诱导的嗜中性粒细胞化学引诱物和次要坏死因子-α）。肾组织血流量减少然而，与CGRP预处理显着改善这些changes.Conclusions：我们的研究结果表明，在缺血/再灌注引起的急性肾损伤的病理过程中的感觉神经元的激活。这种激活通过增强内皮细胞PGI（2）的产生减弱炎症反应来减少急性肾损伤。
Background: Prostaglandin I(2) (PGI(2)) produced by endothelial cells improves ischemia/reperfusion-induced acute renal injury by inhibiting leukocyte activation in rats. However, the underlying mechanism(s) of increased PGI(2)., production is not fully understood. Activation of sensory neurons increases endothelial PGI(2) production by releasing calcitonin gene-related peptide (CGRP) in rats with hepatic ischemia or reperfusion. We examined here whether activation of sensory neurons increases PGI(2) endothelial production, thereby reducing ischemia/reperfusion-induced acute renal injury.Methods: Anesthetized rats were subjected to 45 min of renal ischemia/reperfusion. Rats were pretreated with CGRP, capsazepine (a vanilloid receptor-1 antagonist), CGRP(8-37) (it CGRP receptor antagonist), or indomethacin a cyclooxygenase inhibitor or subjected to denervation of primary sensory nerves before ischemia/reperfusion.Results: Renal tissue levels of CGRP and 6-keto-prostaglandin F(1 alpha), a stable metabolite of PGI(2), increased after renal ischemia/reperfusion. peaking at 1 h after reperfusion. Overexpression of CGRP was also noted at 1 h after reperfusion. Increases in renal tissue levels of 6-keto-prostaglandin F(1 alpha) at 1 h after reperfusion were significantly inhibited by pretreatment with capsazepine. CGRP(8-37)). and indomethacin. Pretreatment with capsazepine. CGRP(8-37). indomethacin, and denervation of primary sensory nerves significantly increased blood urea nitrogen and serum creatinine levels, renal vascular permeability, renal tissue levels (of myeloperoxidase activity, cytokine-induced neutrophil chemoattractant, and minor necrosis factor-alpha. and decreased renal tissue blood flow. However, pretreatment with CGRP significantly improved these changes.Conclusions: our results suggest activation of sensory neurons in the pathologic process of ischemia/reperfusion-induced acute renal injury. Such activation reduces acute renal injury by attenuating inflammatory responses through enhanced endothelial PGI(2) production.