PKCβⅡ特异性抑制剂LY333531减缓心肌梗死后心肌纤维化

PKCβⅡ Selective Inhibitor LY333531 Attenuates Myocardial Infarction Induced Fibrosis

目的:探讨蛋白激酶CβⅡ(PKCβⅡ)特异性抑制剂LY333531对心梗后大鼠心功能和心肌纤维化的保护作用。方法:利用左冠状动脉降支(LAD)结扎制备大鼠心梗模型,将手术4周后出现心衰的大鼠分为模型组(MF+NS)和治疗组(MF+LY333531),分别给予生理盐水和LY333531(10 mg/kg/d)处理6周,检测各组大鼠体重和各项心功能指标,利用HE染色观察各组大鼠心肌组织形态变化,利用天狼星红染色观察心肌组织胶原沉积情况。结果:相对于模型组,LY333531处理组大鼠左心室缩短率(FS)明显改善(从21%到35%)。HE染色显示LY333531能够部分逆转心衰大鼠心室壁肥厚和心肌细胞宽度,天狼星红染色显示治疗组胶原蛋白沉积降低150%。结论:使用LY333531选择性抑制PKCβⅡ能够改善心梗后心力衰竭模型大鼠心脏功能和抑制心肌纤维化。

Objective： To investigate the protective effects of protein kinase C βII （PKCβII） selective inhibitor LY333531 on the myocardial fibrosis after myocardial infarction （MI）. Methods： The left anterior descending （LAD） coronary artery of male Sprague-Daw- ley （SD） rats was occluded to induce MI. At four weeks after MI, rats with heart failure （HF） signs were treated with the LY333531 （3 mg/kg/day） or normal sodium （NS） for 6 weeks. The body weight and cardiovascular parameters were detected. Cardiomyocyte hypertro- phy was evaluated by haematoxylin and eosin （H＆E） staining. Collagen deposition was evaluated by picrosirius red staining. Results： LY333531 treatment improved fractional shortening （from 21% to 35 %） compared to control （NS）. Mid-ventricle tissue sections stained with （H＆E） showed that LY333531 treatment reduced wall thickness and cardiomyocyte width. Picrosirius red staining exhibited a 150 % decrease in collagen deposition in rat hearts treated with LY333531. Conclusions： Sustained selective inhibition of LY333531 in a post-MI HF rat model improves cardiac function and is associated with inhibition of pathological myocardial remodeling.