后适应渐进模式通过线粒体途径减轻大鼠心肌缺血再灌注损伤  

Gradual algorithm of postconditioning reduced reperfusion injury through mitochondrion pathway in rats

作　　者：张国明[1] 王禹[1] 李天德[1] 张大为[1] 刘秀华[2] 杨菲菲[1] 张慧[1] 孙瑜[1] 张亮[1] 

机构地区：[1]解放军总医院心血管病中心心内科,北京100853 [2]解放军总医院基础所病理生理学教研室

出　　处：《中华心血管病杂志》2010年第6期539-544,共6页Chinese Journal of Cardiology

基　　金：国家自然科学基金资助项目（30740080）

摘　　要：目的 探讨后适应不同模式对大鼠急性心肌缺血再灌注损伤的影响,并进一步研究线粒体途径在其中的作用.方法 60只SD大鼠随机分为假手术（Sham）组、缺血再灌注（R/I）组、后适应逆向模式（R-Post,后适应处理方案短暂再灌注/缺血时间为30/10 s,25/15 s,15/25 s,10/30 s）组、后适应标准模式（S-Post,后适应处理方案为20/20 s x 4）组和后适应渐进模式（G-Post,后适应处理方案短暂再灌注/缺血时间为10/30 s,15/25 s,25/15 s,30/10 B）组,共5组,建立急性心肌梗死再灌注和缺血后适应模型.再灌注6 h后每组取4只处死,取心肌组织用Western blot方法测定B细胞淋巴瘤/自血病-2（Bcl-2）、B细胞淋巴瘤/白血病-2相关抗原（Bax）、半胱氨酸天冬氨酸蛋白酶-9（Caspase-9）在心肌组织中的表达及细胞色素C（Cyt-c）在胞浆中的表达.各组其余大鼠再灌注24 h后测定血液动力学,抽血测心肌酶,取心脏进行TUNEL凋亡检测和梗死面积测定.结果 三种后适应处理方案Bax、Cyt-c、Caspase-9、凋亡指数、心肌酶释放均显著低于R/I组（P均〈0.05）,同时三种后处理方案Bcl-2水平均显著高于R/I组（P均〈0.05）,其中G-Post组最为明显,其次是S-Post组,R-Post组最不明显.G-Post组同S-Post组比较,Bax（0.35±0.10比0.50±0.02,P〈0.05）、Cyt-c（O.66±0.16比1.68±0.22,P〈0.05）、Caspase-9（0.61±0.17比1.66±0.55,P〈0.05）的表达水平均较低,心肌酶释放水平低[CK：（251.00±45.16）U/L比（388.56±75.01）U/L,P〈0.05;CK-MB：（146.00±60.12）U/L比（291.16±52.41）U/L,P〈0.05],凋亡指数小[（4.32 ±1.16）%比（8.58 ±1.12）%,P〈0.05].同时Bcl-2表达水平高于S-Post组（2.00 ±0.34比1.40±0.18,P〈0.05）.在以上指标中渐进模式均显著优于逆向模式.结论 后适应渐进模式减轻心肌再灌注损伤程度较标准模式显著,线粒体途径在其中发挥了重要作用.Objective The effects of various postconditioning algorithm on reperfusion injury and the role of mitochondrion pathway were investigated in a rat model of reperfusion/injury. Methods Rats were divided into 5 groups ： sham, reperfusion/injury （ R/I group）, reverse algorithm of postconditioning （ R-Post, 30/10-25/15-15/25-10/30 s of reperfusion/re-occlusion）, standard algorithm of postconditioning （S-Post, 4 cycles of 20/20 s of reperfusion/re-occlusion）, and gradual algorithm of postconditioning （G-Post, 10/30-15/25-25/15-30/10 s of reperfusion/re-occlusion）. Results The levels of Bax,Cytochrome-c, Caspase-9, serum marker of myocardium and apoptosis index were significantly lower while the level of Bcl-2 was significantly higher in the three postconditioning groups than those in R/I group （ all P 〈0. 05）. The levels of Bax （0. 35 ± 0. 10 vs. O. 50 ± 0. 02, P 〈 0. 05）, Cytochrome-c （0. 66 ± 0. 16vs. 1.68 ±0.22, P 〈0.05）, Caspase-9 （0.61 ±0. 17 vs. 1.66 ±0.55, P 〈0.05）, serum marker of myocardium[CK： （251.00 ±45. 16）U/L vs. （388.56 ±75.01） U/L, P〈0.05; CK-MB： （146.00 ±60. 12） U/L vs. （291.16 ± 52. 41 ） U/L, P 〈 0. 05] and apoptosis index [（4. 32 ± 1.16） % vs. （ 8.58 ±1.12 ） %, P 〈 0. 05] were all significantly lower while Bcl-2 level （2. 00 ± 0. 34 vs. 1.40 ± 0. 18, P 〈 0. 05 ）was significantly higher in G-Post group than those in S-Post group. Moreover, above mentioned cardiac protective effects were significantly stronger in the G-Post group compared to R-Post group （ all P 〈 0. 05 ）.Conclusion In conclusion, gradual algorithm of postconditioning could attenuate reperfusion injury more significantly than standard algorithm, and mitochondrion pathway plays an important role in this cardioprotective process.

关 键 词：心肌再灌注损伤 线粒体 后适应 

分 类 号：R542.22[医药卫生—心血管疾病]