降钙素基因相关肽在前列腺素介导豚鼠心脏缺血预适应中的作用

摘要

目的：研究降钙素基因相关肽与前列腺素在豚鼠心脏缺血预适应中的相互作用.方法：采用Langen-dorff方法灌注豚鼠离体心脏.记录心率、冠脉流量、左室内压以及最大变化速率，并测定冠脉流出液中降钙素基因相关肽(CGRP)与6-酮-PGFlα的释放量.结果：内皮素-1(200 pmoL)引起心功能下降，表现为冠脉流量、心率、左室内压及其最大变化速率降低.缺血预适应可明显减轻内皮素-1引起的心脏损伤，同时预适应期间CGRP与6-酮-PGF1α的释放量明显增加.应用辣椒素耗竭内源性CGRP后，缺血预适应的保护作用被取消.选择性CGRP1受体拮抗剂CGRP8-37 100 nmol/L也能取消缺血预适应的保护作用.环氧化酶抑制剂吲哚美辛(10 μmol/L)可取消缺血预适应的保护作用，同时缺血预适应促进CGRP与6-酮-PGF1α释放的作用也被取消.结论：前列腺素参与了缺血预适应对豚鼠心脏的保护作用，前列腺素的作用是由CGRP所介导.%AIM: To examine the role of calcitonin gene-related peptide (CGRP) in ischemic preconditioning induced by prostaglandins in isolated guinea pig hearts. METH ODS: The isolated guinea pig hearts were perfused in a Langendorff model. The heart rote, coronary flow, left ventricular pressure, and its first derivatives (±dp/dtmax) were recorded and the calcitonin gene-related pep tide-like immunoreactivity (CGRP-LI) and 6-keto-PGF1α were measured. RESULTS: Endothelin-l (200 pmol in 1 mL K-H buffer) reduced the left ventricular developed pressure and its first derivatives (±dp/dtmax), heart rote, and coronary flow. Preconditioning with two cycles of 5-min global ischemia and 5-main reperfusion attenuated endothelin-l-induced myocardial injury, and concentrations of both CGRP and 6-keto-PGF1α in the coronary effluent were markedly raised in the preconditioning periods. Pretreaunent with capsaicin, which depletes endogenous CGRP, abolished the elevated level of CGRP concomitantly with loss of the cardioprotection in duced by ischemic preconditioning. CGRP8-37 (100 mol/L), a selective CGRP1 receptor antagonist, also abolished the protective effects of ischemic preconditioning. After pretreatment with indometacin (10 μmol/L), an inhibitor of cyclooxygenase, the protective effects of ischemic preconditioning were abolished and the release of 6-keto-PGF1α was no longer elevated. Pretreatment with indometacin abolished the elevated level of CGRP in the coronary effluent. CONCLUSION: Endogenous prostaglandins are involved in the protective effects of is chemic preconditioning, and the beneficial effects of prostaglandins are mediated by CGRP in the guinea pig heart.