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辣椒素激活瞬时受体电位香草醛亚型 1 减轻兔肺缺血再灌注损伤。

TRPV1 agonist capsaicin attenuates lung ischemia-reperfusion injury in rabbits.

机构信息

Department of Anesthesiology, and Laboratory of Anesthesia and Intensive Care Medicine, West China Hospital of Sichuan University, Chengdu, Sichuan, China.

出版信息

J Surg Res. 2012 Mar;173(1):153-60. doi: 10.1016/j.jss.2010.08.053. Epub 2010 Sep 27.

DOI:10.1016/j.jss.2010.08.053
PMID:20950828
Abstract

BACKGROUND

Capsaicin, a transient receptor potential vanilloid type 1 (TRPV1) agonist, was found to protect against myocardial and renal ischemia-reperfusion (IR) injury. This study was carried out to investigate the role of capsaicin in lung IR injury in vivo.

METHODS

Forty male New Zealand rabbits were randomized into four groups (10 per group) as follows: sham group (sham thoracotomy), IR group (occlusion of the left pulmonary hilus for 1 h followed by reperfusion for 3 h), CAP (capsaicin) group (a bolus injection of CAP 5 min before ischemia), CPZ (capsazepine) group (a bolus injection of the TRPV1 antagonist CPZ 5 min before ischemia). Blood and lung tissue samples were obtained for blood gas and biochemical analyses, wet/dry weight ratio measurements, and histologic evaluation. Protein levels and neutrophils in the bronchoalveolar lavage fluid (BALF) were also measured.

RESULTS

Pretreatment with capsaicin improved gas exchange function, decreased lung wet/dry ratio and protein levels and neutrophil counts in BALF, decreased lung malondialdehyde levels and myeloperoxidase activities, increased superoxide dismutase activities, along with an elevation of calcitonin gene-related peptide (CGRP) level (P < 0.05 versus IR group). Capsaicin also attenuated IR-induced pathological lesions. By contrast, capsazepine exacerbated gas exchange abnormality, increased pulmonary microvascular permeability, oxidative stress, neutrophils infiltration, and also revealed a decreased CGRP level (P < 0.05 versus IR group).

CONCLUSION

Results from the present study show that capsaicin confers protection against lung IR injury. These protective effects seem to be closely related to the inhibition of inflammation and oxidative stress via the activation of TRPV1 and the release of CGRP.

摘要

背景

辣椒素是一种瞬时受体电位香草素 1(TRPV1)激动剂,已被发现可预防心肌和肾缺血再灌注(IR)损伤。本研究旨在探讨辣椒素在体内肺 IR 损伤中的作用。

方法

40 只雄性新西兰兔随机分为 4 组(每组 10 只):假手术组(开胸假手术)、IR 组(左肺门阻断 1 h 后再灌注 3 h)、CAP 组(缺血前 5 min 给予辣椒素冲击)、CPZ 组(缺血前 5 min 给予 TRPV1 拮抗剂 CPZ 冲击)。取血和肺组织标本进行血气和生化分析、湿/干重比测量和组织学评估。还测量了支气管肺泡灌洗液(BALF)中的蛋白水平和中性粒细胞。

结果

辣椒素预处理改善了气体交换功能,降低了肺湿/干重比和 BALF 中的蛋白水平和中性粒细胞计数,降低了肺丙二醛水平和髓过氧化物酶活性,增加了超氧化物歧化酶活性,同时提高了降钙素基因相关肽(CGRP)水平(与 IR 组相比,P < 0.05)。辣椒素还减轻了 IR 引起的病理损伤。相比之下,辣椒素拮抗剂 Capsazepine 加重了气体交换异常,增加了肺微血管通透性、氧化应激、中性粒细胞浸润,并显示 CGRP 水平降低(与 IR 组相比,P < 0.05)。

结论

本研究结果表明,辣椒素对肺 IR 损伤具有保护作用。这些保护作用似乎与通过激活 TRPV1 和释放 CGRP 抑制炎症和氧化应激密切相关。

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