T型钙通道拮抗剂对未成熟心肌缺血再灌注损伤的保护作用  

Myocardiol Protection of T Type Calcium Channel Blocker Against Ischemia-Reperfusion Injury in Immature Rabbit Heart

作　　者：唐浩[1] 周新民[1] 胡建国[1] 肖献忠[2] 胡野荣[1] 杨一峰[1] 彭昊[1] 李津[1] 喻杰锋[1] 

机构地区：[1]中南大学湘雅二医院胸心外科,湖南省长沙市410011 [2]中南大学湘雅医学院病理生理学教研室,湖南省长沙市410078

出　　处：《中国动脉硬化杂志》2005年第4期435-438,共4页Chinese Journal of Arteriosclerosis

摘　　要：目的探讨T型钙通道拮抗剂Mibefradil对未成熟心肌缺血再灌注损伤的保护作用。方法2～3周龄新西兰大白兔32只随机分为4组:ST组为St.Thomas液停搏,SV组为St.Thomas液中加入0.1μmolLVerapamil,SM1组为St.Thomas液中加入0.1μmolLMibefradil,SM2组为St.Thomas液中加入1μmolLMibefradil。建立Langendorff模型后,分别在4℃按上述心脏停搏液停搏,维持局部心肌温度在15℃,停止灌注90min,再灌注45min。观测各组停搏前、再灌注后冠状动脉流量、冠状动脉流出液乳酸脱氢酶浓度、心功能(左心室发展压、左心室内压最大上升下降速率)恢复率、心肌丙二醛含量和心肌钙离子含量等指标。结果各组冠状动脉流量没有明显差异。心功能恢复发现再灌注后45min时,SV组的左心室发展压、左心室内压最大上升下降速率恢复率分别为:0.70±0.23、0.72±0.23和0.67±0.25,明显低于其余各组(P<0.05),其余各组之间没有明显差异。SV组乳酸脱氢酶浓度(12.2±2.7IUL)明显高于其他各组(P<0.05),同时ST组(9.3±3.2IUL)也明显高于SM2组(6.6±2.2IUL),P<0.05。心肌丙二醛含量ST组(1.64±0.39μmolg)和SV组(1.76±0.51μmolg)明显高于SM2组(1.14±0.24μmolg,P<0.05)。SV组心肌钙离子含量(0.225±0.041mgg)明显高于其他各组(P<0.05)。同时ST组(0.184±0.021mgg)也明显高于SM2组(0.147±0.020mgg,P<0.05)。结论Mibefradil对未成熟心肌缺血再灌注损伤有保护作用,Verapamil损害未成熟心肌。Aim This study was designed to identify the T-type calcium channjel blocker Mibefradil as a cardioplegic agent in terms of its efficacy in immature cardioprotection. Methods By a Langendorff model, 32 hearts of 14- to 21-dey-old New Zealand rabbits underwent 90 min of global hypothermic （ 15℃ ） isohemia protected with a different single dose of hypothermic （4℃） cardioplegia（ group ST： St. Thomas solution; group SV： St. Thomas solution combined with 0.1 μmol/L Verapamil; group SM1：St. Thomas solution combined with 0.1 μmol/L Mibefradil;group SM2： St. Thomas solution combined with 1 μmol/L Mibefradil）, The coronary flux, percent recovery of the cardiac function, IDH release, myocardium MDA, and myocardium ionized calcium were compared. Results Them are no significant difference in coronary flux between the groups. Verapamil provided significantly the worst postreperfused percentage recovery of the cardiac function （developed pressure： 0.70±0.23, dp/dt： 0.72±0.23, and-dp/dt：0.67±0.25） than the other groups（P〈0.05）. There are no significant differenee in the cardiae function between others groups. The higher concentration Mibefradil （ 1 μmol/L） showed a significant reduction of LDH release （6.6±2.2 IU/L vs 9.3±3.2 IU/L）in the coronary flow, and lower myocardium MDA （1.14±0.24 μmol/g vs 1.64 ±0.39 μmol/g） and ionized calcium（0.147±0.020mg/g vs 0.1842±0.021 mg/g） than group ST（P〈0.05）. Verapamil showeda highest LDH release （ 12.2 ± 2.7 IU/L） in the coronary flow and myocardium ionized calcium （ 0. 225 ± 0. 041 mg/g） （ P 〈 0.05 ）. Conclusion St. Thomas solution combined with Mibefradil provided better protection during ischemia-reperfusion in the immature rabbit heart than St. Thomas＇ solution, whereas St. Thomas＇ solution combined with Verapamil showed the worst protective effects in immature hearts.

关 键 词：病理学与病理生理学 T型钙通道阻断剂 MIBEFRADIL 缺血再灌注损伤 未成熟心肌 心肌保护 兔 

分 类 号：R363[医药卫生—病理学]