摘要
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.
出处
《现代生物医学进展》
CAS
2017年第17期3234-3237,3273,共5页
Progress in Modern Biomedicine
基金
国家自然科学基金项目(81300956)
陕西省自然科学基础研究计划面上项目(2016JM3005)