Role of sensory neuron in reduction of endotoxin-induced hypotension in rats
Role of sensory neuron in reduction of endotoxin-induced hypotension in rats
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DOI：
10.1097/01.ccm.0000159721.72629.49
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发表时间：
2005-04-01
影响因子：
8.8
通讯作者：
Harada, N
中科院分区：
文献类型：
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作者：
Okajima, K;Isobe, H;Harada, N
目的：我们试图确定感觉神经元的激活是否有助于通过抑制大鼠降钙素基因相关肽（CGRP）释放产生肿瘤坏死因子（TNF）-α来减少内毒素诱导的低血压。设计：前瞻性、随机、对照研究。销售：大学医学中心的研究实验室。受试者：体重220-280 g的Wistar大鼠。干预措施：在静脉注射内毒素的大鼠中测量平均动脉血压。在给予内毒素之前，用辣椒平（一种香草素受体拮抗剂）、CGRP（8-37）（一种CGRP受体拮抗剂）和吲哚美辛预处理动物。采用酶免疫分析法测定CGRP、6-酮-前列腺素F-1 α、TNF-α和马槟榔诱导的中性粒细胞趋化因子（CINC）水平。用Griess试剂测定NO2-/NO3-浓度。组织水平的信使RNA的诱导型一氧化氮合酶（iNOS）和TNF-α的测定通过逆转录聚合酶链reaction. Measures和主要结果：两个肺CGRP水平和血浆水平的6-酮-前列腺素F-1 α静脉注射内毒素（5毫克/公斤）后增加，峰值在90分钟内毒素管理。内毒素给药后90分钟6-酮-前列腺素F-1 α的血浆水平升高通过用辣椒平（373 +/-44 pg/mL，p <0.05）、CGRP（8-37）（406 +/-64 pg/mL，p <0.05）和吲哚美辛（154 40 pg/mL，p <0.05）预处理来抑制（766 +/-134 pg/mL）。尽管没有一种预处理影响一系列内毒素诱导的反应，包括给予5 mg/kg内毒素的动物肺组织TNF-α、CINC和NOS水平的增加以及由此产生的低血压，但这种预处理增强了给予较小剂量内毒素的动物的这些病理反应（11 mg/kg）与5 mg/kg内毒素诱导的程度相同，提示5 mg/kg内毒素诱导的休克反应是内毒素诱导的感觉神经元的最大反应和激活，治疗大鼠基本上是一种修复性反应。感觉神经元的激活可能通过释放能够促进内皮细胞产生前列环素的CGRP而有助于减少内毒素诱导的低血压。
Objective: We attempted to determine whether activation of the sensory neuron contributes to reduction of endotoxin-induced hypotension by inhibiting tumor necrosis factor (TNF)-alpha production via calcitonin gene-related peptide (CGRP) release in rats.Design: Prospective, randomized, controlled study.Selling: Research laboratory at a university medical center.Subjects: Wistar rats weighing 220-280 g.Interventions: Mean arterial blood pressure was measured in rats administered endotoxin intravenously. Animals were pretreated with capsazepine (a vanilloid receptor antagonist), CGRP(8-37) (a CGRP receptor antagonist), and indomethacin before endotoxin administration. Levels of CGRP, 6-keto-prostaglandin F-1 alpha, TNF-alpha, and cytokine-induced neutrophil chemoattractant (CINC) were measured by enzyme immunoassay methods. The concentration of NO2-/NO3- was measured using the Griess reagent. Tissue levels of messenger RNA of the inducible form of nitric oxide synthase (iNOS) and TNF-alpha were determined by reverse transcription polymerase chain reaction.Measurements and Main Results: Both lung levels of CGRP and plasma levels of 6-keto-prostaglandin F-1 alpha were increased after intravenous administration of endotoxin (5 mg/kg), peaking at 90 mins after endotoxin administration. Increases in plasma levels of 6-keto-prostaglandin F-1 alpha at 90 mins after endotoxin administration (766 +/- 134 pg/mL) were inhibited by pretreatment with capsazepine (373 +/- 44 pg/mL, p < .05), CGRP(8-37) (406 +/- 64 pg/mL, p < .05), and indomethacin (154 40 pg/mL, p < .05). Although none of the pretreatments affected a series of endotoxin-induced responses, including increases in lung tissue levels of TNF-alpha, CINC, and NOS and the resultant hypotension in animals given 5 mg/kg endotoxin, such pretreatments enhanced these pathologic responses in animals given a smaller dose of endotoxin (11 mg/kg) to the same extent as those induced by 5 mg/kg of endotoxin, suggesting that shock responses induced by 5 mg/kg endotoxin are maximum responses and activation of sensory neurons in endotoxin-treated rats is essentially a reparative response.Conclusion. Activation of sensory neurons might contribute to reduction of endotoxin-induced hypotension by releasing CGRP, which is capable of promoting endothelial production of prostacyclin.