摘要
目的探讨广谱氯离子通道阻滞剂4,4’-二异硫氰基芪2,2’-二磺酸(DIDS)对大鼠缺血再灌注损伤心肌细胞凋亡的影响及其机制。方法雄性SD大鼠36只随机分为3组:缺血再灌注组(A组)、DIDS处理组(B组)和LY294002预处理组(C组)。伊文兰和TTC染色测定心肌梗死范围,TUNEL方法定性和定量检测心肌细胞凋亡指数,Western blot测定蛋白激酶B(Akt)的表达。结果与A组比较,B组心肌梗死范围和心肌细胞凋亡指数明显降低[(38.8±7.7)% vs (54.2±10.8)%,(8.9±1.8)% vs (17.6±3.5)%.P<0.01];磷酸化Akt表达水平明显增加(P<0.01)。与A组比较,C组梗死面积、凋亡指数无明显减小,磷酸化Akt水平无明显变化(P>0.05)。结论 DIDS能够抑制大鼠缺血再灌注所致的心肌细胞损伤,可能是通过信号分子磷脂酰肌酶三羟基激酶/Akt的调节。
Objective To investigate the effect of 4,4＇-diisothiocyanostilbene-2,2＇-disulfonic acid （DIDS） ,a non-selective chloride channel blocker,on rat myocardium ischemia-reperfusion injury and its mechanisms. Methods Thirty-six male Sprague-Dawley rats were divided into 3 groups randomly：ischemia-reperfusion group（group A）,DIDS treatment group（group B） and LY294002 pretreatment group（group C）. The size of myocardial infarct was determined by Evan＇s blue and triphenyl tetrazolium chloride methods; the cardiomyocyte apoptosis index was determined both qualitatively and quantitatively by terminal deoxynucleotidyl transferase-mediated dUTP by nickend labeling analysis methods. The expression of protein kinase B（Akt） signaling cascade was determined by Western blot analysis. Results Compare with group A,the size of myocardial infarct and cardiomyocyte apoptosis index in group B were significantly attenuated[（38. 8 ± 7. 7）% vs （54.2±10.8） % ,（8.9±1.8）% vs （17. 6±3. 5）%, P 〈 0.01];the expression of phosphorylated Akt was heightened significantly （P 〈 0.01）. Compared with group A,the size of myocardial infarct and cardiomyocyte apoptosis index were not significantly attenuated, and the expression of phosphorylated Akt was not changed significantly （P 〈 0.05） in group C. Conclusion The results suggest that DIDS may be able to protect the heart against ischemia reperfusion-induced injury through the regulation of signaling molecules PI3K/Akt.
出处
《中华老年心脑血管病杂志》
CAS
北大核心
2009年第12期965-967,共3页
Chinese Journal of Geriatric Heart,Brain and Vessel Diseases
基金
国家自然科学基金(30570758
30770847)
陕西省社会发展项目[(2005K13-G1(4)]
