KB-R7943与缺血后适应在高脂饮食大鼠心肌缺血再灌注损伤中保护作用  

Protective effect of Na^+/Ca^(2+) exchange blocker KB-R7943 on myocardial ischemia-reperfusion injury in hypercholesterolemic rats

作　　者：吕岩[1] 贾大林[1] 

机构地区：[1]中国医科大学附属第一医院心内科,辽宁沈阳110001

出　　处：《临床军医杂志》2016年第2期115-118,123,共5页Clinical Journal of Medical Officers

基　　金：辽宁省自然科学基金(2013021011)

摘　　要：目的探讨选择性Na^+/Ca^(2+)交换抑制剂KB-R7943及缺血后适应在高脂条件下对心肌缺血再灌注损伤的作用。方法 48只大鼠鼠心脏给予完全缺血30 min,之后再灌注120 min。其中,正常饮食喂养大鼠12只作为对照组(C组)。高胆固醇饮食喂养大鼠,缺血后加以处理:12只不干预(高胆固醇对照组,HC组);12只给予KB-R7943(KB-R组);12只给予缺血后3个循环的再灌注和再缺血,每个循环10 s(IPO组)。观察各组大鼠心脏功能,氯化三苯四氮唑染色测量心肌梗死范围、Caspase-3活性及TUNEL染色测定评价凋亡程度。结果血流动力学结果显示,KB-R组和IPO组的心脏功能较HC组有明显提高,差异均有统计学意义(P<0.05)。TTC染色显示,KB组梗死程度最少,IPO组梗死程度低于高脂对照组。IPO组TUNEL阳性心肌细胞低于高脂对照组,KB-R7943组TUNEL阳性心肌细胞明显低于高脂对照组,且与IPO组有组间差异。KB及IPO组Caspase-3活性与高脂对照组比较降低,IPO组与KB组有组间差异。结论 KB-R7943减少高脂大鼠缺血心肌坏死及细胞的凋亡,从而减轻缺血再灌注损伤。高脂条件下与IPO相比,KB-R7943缺血后处理更具有心肌保护作用。Objective To investigate the effect of KB-R7943 and ischemic post-conditioning on myocardial ischemia-reperfusion injury in hyperlipidemia rats. Methods Twelve rats were fed normal chow,while,48 animals were fed a high cholesterol diet. The hearts were subjected to 25 minutes of global ischemia followed by a 120-minute reperfusion. Before this,hearts from hypercholesterolemic rats either received no intervention（ cholesterol control group） or were pre-treated with 1 μm KB-R7943 or 3 circles re-ischemic and re-perfusion. Results KB-R7943 and IPO significantly protected cardiac function. The infarction sizes in the cholesterol control group were significantly more than control group,and the least in the KB-R7943 group. The infarction sizes in the IPO group were lower than cholesterol control group. Further,tunnel positive cell in KB and IPO group were less than cholesterol control group. The activity of Caspase-3 in KB and IPO group were lower than HC group,and there was difference between KB and IPO group. Conclusion KBR7943 reduces the infarction size and apoptosis in hyperlipidemic animals,and relieve the ischemic-reperfusion injury. KB-R7943 was more protective than IPO in hypercholesterol condition.

关 键 词：缺血再灌注损伤 高脂血症 凋亡 钠钙交换阻滞剂 KB-R7943 

分 类 号：R589.2[医药卫生—内分泌]