目的探讨鞘内吗啡预处理对心肌缺血再灌注大鼠背根神经节神经生长因子(NGF)表达的影响。方法鞘内置管成功的健康成年雄性SD大鼠30只,体重250~350g,采用随机数字表法分为5组(n=6):假手术组(S组)、心肌缺血再灌注组(I/R组)、鞘内吗啡预处理组(ITMP组)、“受体阻断剂CTOP+鞘内吗啡预处理组(CTOP+ITMP组)和CTOP对照组(CTOP组)。ITMP组缺血再灌注前30min,经鞘内导管微量泵恒速输注吗啡3μg/kg(10μl)5min,间断5min,重复3次;CTOP+ITMP组和CTOP组分别于吗啡预处理前10rain和缺血前40min鞘内注射1μg/μl CTOP 10μl。于再灌注120min时处死大鼠,取心肌组织,测定心肌梗死体积;取背根神经节,分别采用免疫组化法和Western blot法检测NGF的表达。结果与S组比较,I/R组心肌梗死体积增大,背根神经节NGF表达上调(P〈0.05);与I/R组比较,ITMP组心肌梗死体积减小,背根神经节NGF表达下调(P〈0.05),CTOP组上述指标差异无统计学意义(P〉0.05);与ITMP组比较,CTOP+ITMP组和CTOP组心肌梗死体积增大,背根神经节NGF表达上调(P〈0.05)。结论鞘内吗啡预处理减轻大鼠心肌缺血再灌注损伤的机制与激活脊髓斗受体,抑制背根神经节NGF的表达,减轻伤害性刺激反应有关。
Objective To investigate the effect of intrathecal morphine preconditioning on the expression of nerve growth factor (NGF) in the dorsal root ganglia (DRG) in a rat model of myocardial ischemia-reperfusion (I/R). Methods Thirty healthy adult male Sprague-Dawley rats in which intrathecal catheters were successfully placed without complications, weighing 250-350 g, were randomly divided into 5 groups (n= 6 each) using a random number table: sham operation group (S group) , I/R group, intrathecal morphine preconditioning group ( ITMP group) , μ receptor antagonist CTOP + intrathecal morphine preconditioning group (CTOP + ITMP group), and CTOP control group (CTOP group). Myocardial ischemia was induced by 30 min of occlusion of the anterior descending branch of the left coronary artery followed by 120 rain of reperfusion in all the groups except S group. Intrathecal morphine preconditioning was produced by 3 cycles of 5 min intrathecal injection of morphine 3 μg/kg ( 10 μl) at 5 rain intervals within 30 rain before ischemia in ITMP group. In CTOP+ITMP and CTOP groups, 1 μg/μl CTOP 10 μl was injected intrathecally at 10 rain before morphine preconditioning and 40 rain before ischemia, respectively. At 120 min of reperfusion, the rats were sacrificed, and myocardial specimens were obtained for determination of myocardial infarct size, and DRGs were removed for determination of the expression of NGF by using immunohistochemistry and Western blot. Results Compared with S group, the myocardial infarct size was significantly increased, and the expression of NGF in DRGs was significantly up-regulated in I/R group (P〈 0.05). Compared with I/R group, the myocardial infarct size was significantly decreased, and the expression of NGF in DRGs was significantly down-regulated in ITMP group (P〈 0.05), and no significant change was found in the parameters mentioned above in CTOP group (P〉0.05). Compared with ITMP group, the myocardial infarct size was significantly