Cardioprotection by ischemic postconditioning is lost in isolated perfused heart from diabetic rats: Involvement of transient receptor potential vanilloid 1, calcitonin gene-related peptide and substance P
Cardioprotection by ischemic postconditioning is lost in isolated perfused heart from diabetic rats: Involvement of transient receptor potential vanilloid 1, calcitonin gene-related peptide and substance P
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糖尿病大鼠离体灌注心脏中缺血后处理的心脏保护作用丧失：瞬时受体电位香草酸 1、降钙素基因相关肽和 P 物质的参与
DOI：
10.1016/j.regpep.2011.04.004
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发表时间：
2011-08-08
影响因子：
--
通讯作者：
Chen, Hong
中科院分区：
文献类型：
--
作者：
Ren, Jing-Yi;Song, Jun-Xian;Chen, Hong
我们之前发现糖尿病心脏中瞬时受体电位香草样蛋白1 （TRPV1）的表达以及TRPV1释放的两种主要神经肽降钙素基因相关肽（CGRP）和P物质（SP）的含量降低。本研究旨在检测是否降低TRPV1。CGRP和SP水平与链脲佐菌素诱导的糖尿病大鼠离体灌注心脏缺血后适应（IPostC）保护功能丧失有关。IPostC通过改善心功能，降低肌酸激酶（CK）和心肌肌钙蛋白I （cTnI）的释放，有效保护非糖尿病心脏免受缺血再灌注损伤，而肌酸激酶和肌钙蛋白I的释放可通过抑制TRPV1、CGRP受体或SP受体来消除。然而，无论是否抑制TRPV1、CGRP受体或SP受体，IPostC对糖尿病心脏的心功能和CK、cTnI的释放均无影响。CGRP或sp诱导的后适应通过改善心功能、降低CK和cTnI释放，显著预防非糖尿病和糖尿病心脏缺血/再灌注损伤。此外。IPostC显著增加非糖尿病心脏CGRP和SP的释放，可通过TRPV1抑制逆转，但不能抑制CGRP受体或SP受体。然而，无论是否存在TRPV1、CGRP受体或SP受体抑制，IPostC均不能影响糖尿病心脏中CGRP和SP的释放。这些结果表明，糖尿病期间IPostC对心脏保护作用的丧失部分与不能增加CGRP和SP释放有关，这可能是由于糖尿病心脏中TRPV1表达和CGRP和SP含量降低所致。(C) 2011 Elsevier B.V.版权所有
We previously found that the expression of transient receptor potential vanilloid 1 (TRPV1) and contents of calcitonin gene-related peptide (CGRP) and substance P (SP), two main neuropeptides released from TRPV1, were decreased in diabetic hearts. This study aimed to test whether decreased TRPV1. CGRP and SP levels were responsible for the loss of cardioprotection by ischemic postconditioning (IPostC) in isolated perfused heart from streptozotocin-induced diabetic rats. IPostC effectively protected non-diabetic hearts against ischemia/reperfusion injury by improving cardiac function and lowering creatine kinase (CK) and cardiac troponin I (cTnI) release, which could be abolished by inhibiting TRPV1, CGRP receptor or SP receptor. However, IPostC had no effect on cardiac function and the release of CK and cTnI in diabetic hearts regardless of whether TRPV1, CGRP receptor or SP receptor were inhibited. CGRP or SP-induced postconditioning significantly prevented both non-diabetic and diabetic hearts from ischemia/reperfusion injury by improving cardiac function and lowering CK and cTnI release. Additionally. IPostC markedly increased CGRP and SP release in non-diabetic hearts, which could be reversed with TRPV1 inhibition, but not CGRP receptor or SP receptor inhibition. However, IPostC failed to affect CGRP and SP release in diabetic hearts in the presence or absence of TRPV1, CGRP receptor or SP receptor inhibition. These results indicate that the loss of cardioprotection by IPostC during diabetes is partly associated with a failure to increase CGRP and SP release, likely due to decreased TRPV1 expression and CGRP and SP contents in diabetic hearts. (C) 2011 Elsevier B.V. All rights reserved.