盐酸右美托咪定预处理对急性心肌缺血大鼠心肌P物质和降钙素基因相关肽的影响

摘要

目的：观察盐酸右美托咪定预处理对急性心肌缺血大鼠心肌组织缺血区和非缺血区P物质（SP）和降钙素基因相关肽（CGRP）表达的影响。方法健康成年雄性SD大鼠30只，体质量270~300 g，按随机数字表法分为假手术组（S组）、单纯冠状动脉结扎组（I组）和盐酸右美托咪定预处理冠状动脉结扎组（D组），每组10只。 S组大鼠开胸后在冠状动脉左前降支下穿线不结扎；I组大鼠开胸后结扎冠状动脉左前降支；D组大鼠在结扎冠状动脉左前降支前15 min经尾静脉给予盐酸右美托咪定5μg/kg。各组在手术后计时3 h。采用免疫组织化学、酶联免疫和反转录-聚合酶链反应法从蛋白和基因水平观察各组大鼠缺血区和非缺血区心肌 SP和CGRP的表达。结果 I组大鼠缺血区心肌SP/SP mRNA和CGRP/β-CGRP mRNA的水平较S组升高（P＜0.05），D组低于I组（P＜0.05），但仍高于S组（P＜0.05）。非缺血区各组的变化趋势类同缺血区，但各扎闭冠状动脉组SP/SP mRNA和CGRP/β-CGRP mRNA的水平均低于相应组缺血区的水平（P＜0.05）。结论盐酸右美托咪定预处理可降低急性心肌缺血大鼠心肌组织SP和CGRP的表达，提示盐酸右美托咪定预处理可能参与缺血心肌的保护。%Objective To investigate the effects of preconditioning with hydrochloride dexmedetomidine on the expression of substance P (SP) and calcitonin gene-related peptide (CGRP) in ischemic and non-ischemic area of my-ocardium in rats with acute myocardial ischemia. Methods Thirty adult male SD rats weighing 270~300 g were ran-domly divided into three groups (n=10 each), the sham operation group (group S), simple coronary artery ligation group (group I), and hydrochloride dexmedetomidine preconditioning and coronary artery ligation group (group D). The left anterior descending branch of coronary artery was threaded without ligation after thoracotomy in group S. The left an-terior descending branch of coronary artery was ligatd after thoracotomy in group I. Group D was given 5 μg/kg hy-drochloride dexmedetomidine intravenously by tail at 15 min before ligation of the left anterior descending branch of coronary artery. The SP and CGRP protein and gene expression in the ischemic and non-ischemic area of myocardium were determined by immunohistochemistry, enzyme-linked immunosorbent assay, and reverse transcription-polymerase chain reaction. Results The SP/SP mRNA and CGRP/β-CGRP mRNA levels in ischemic myocardium in group I were significantly increased compared with those in group S (P<0.05). The SP/SP mRNA and CGRP/β-CGRP mRNA levels in ischemic myocardium in group D were lower than those in group I ( P<0.05), whereas higher than those in group S (P<0.05). A similar trend was found in non-ischemic myocardium in all groups. However, the SP/SP mRNA and CGRP/β-CGRP mRNA levels in ischemic myocardium in the groups with coronary artery ligation were lower than those than in non-ischemic myocardium (P<0.05). Conclusion Preconditioning with hydrochloride dexmedetomidine may decrease the SP and CGRP expression in myocardium in rats with acute myocardial ischemia, suggesting that it may be involved in the protection of ischemic myocardium.