右美托咪啶后处理对大鼠离体心脏缺血再灌注的影响

目的 探讨右美托咪啶后处理对大鼠离体心脏缺血再灌注的影响.方法 健康雄性Wistar大鼠48只成功制备Langendorff离体灌注模型,随机分为4组各12只：假手术组（C组）,缺血再灌注组（I/R组）、右美托咪啶10nmol/L组（DⅠ组）、右美托咪啶100nmol/L组（DⅡ组）,离体心脏经K-H液平衡灌注20min后,除C组外均采用全心停灌40min再灌注120min的方法,制备离体心脏缺血再灌注模型.DⅠ组和DⅡ组于再灌注即刻分别灌注含10nmol/L右美托咪啶和100 nmol/L右美托咪啶的K-H液20 min,然后继续用K-H液再灌注120 min.用多通道生理信号采集处理系统分别记录各个时刻的冠脉流出量（CF）、心率（HR）和左心室发展压（LVEDP）、室内压最大上升速率（＋dp/dtmax）和室内压最大下降速率（-dp/dtmax）.再灌注结束即刻取心尖组织,免疫组化法检测Bcl-2和 Bax蛋白的表达,用TUNEL法检测心肌细胞凋亡情况.结果 与I/R组比较,DⅠ组和DⅡ组在t3、t4、t5时LVDP和±dp/dtmax均升高（P均＜0.05）,CF在t4、t5升高（P均＜0.05）;Bcl-2蛋白表达增高,Bax蛋白表达降低（P均〈0.05）;DⅠ组和DⅡ组凋亡细胞比I/R 组明显减少.结论 右美托咪啶后处理能够改善缺血再灌注左心室功能,减轻心肌缺血再灌注损伤,其机制可能与右美托咪啶可上调心肌Bcl-2蛋白表达,下调Bax蛋白表达,减少心肌细胞凋亡有关.

Effects of dexmedetomidine postconditioning on ischemia-reperfusion injury to isolated rat hearts

Objective It is to approach the influence of dexmedetomidine postconditioning on ischemia-reperfusion （I/R） injury to isolated rat hearts. Methods Forty-eight male Wistar rats were selected, and the Langendorff model were successfully prepared, then were randomly divided into 4 groups of equilibration （ n = 12 each） ： sham group （ group C） , I/R group （groups I/R） , dexmedetomidine 10 nmol/L postconditioning group （group DI） , dexmedetomidine 100 nmol/L posteonditioning group （group D H ）. After the excised hearts were perfuse for 20 min with K - H solution, except group C, myocardial I/ R injury were induced by 40 min of global ischemia followed by 120 min of reperfusion with K -H solution. In groups D Ⅰ and D Ⅱ , the hearts were perfused with K - H solution containing dexmcdetomidine 10 nmol/L or 100 nmol/L for 20 min followed by 10 min washout after ischemia. Coronary flow （CF） , left ventricular developed pressure （LVDP） , ± dp/dtmax and HR were measured at 20 min of equilibration, immediately before ischemia, at 40 min of ischemia, at 30min, 60min and 120 min of reperfusion. Myocardial tissues were obtained at the end of reperfusion for determination of the expression of Bcl - 2 and Bax protein levels by immunohistochemistry, TUNEL was used to analyze apoptotic index. Results Compared with group I/R, LVDP and ＋ dp/dtmax were significantly elevated at t3 , t4 , t5 （ all P 〈 0.05） , and CF was significantly increased at T4, T5 （ all P 〈 0.05 ） ; the expression of Bcl - 2 protein were significantly increased, and the expression of Bax protein were significantly decreased in groups D Ⅰ and D Ⅱ （P 〈 0.05）. Apoptotic cells of group D Ⅰ and D Ⅱ were reduced significantly than group 1/R. Conclusion Dexmedetomidine preconditioning can improve left ventricular function, and attenuate myocardial I/R injury in isolated rat hearts, which mechanism may be related to inhibit the apoptosis of myocardium by up-regulating the expression of Bel -2 and down-regulating the expression of Bax protein.