摘要
目的探讨七氟烷后处理对大鼠离体心脏缺血/再灌注的保护作用。方法48只SD大鼠,随机分为4组(n=12):假手术组(Sham),缺血/再灌注组(I/R)缺血后处理组(Post),七氟烷后处理组(Sevo)。采用Langendroff离体心脏灌注模型。除Sham组其余各组均平衡灌注30min,全心缺血30min,再灌注90min,Post组在再灌注即刻给予4个循环复灌20s/缺血20s,Sevo组在再灌注开始给予含1.5MAC(2.57V/V)七氟烷的K-H液灌注5min,再用K-H液冲洗10min,纪录平衡灌注末,再灌注30min、60min、90min时左室舒张末压(LVEDP)、左室发展压(LVDP)、左室内压上升最大速率(+dp/dt)、左室内压下降最大速率(-dp/dt)、心率(HR)、冠脉血流量(CF),再灌注90min时,计算心肌梗死面积百分比,电子显微镜观察线粒体的损伤程度,Westernblot半定量测定胞质和线粒体、细胞色素C的水平。结果平衡灌注末各组间心功能指标(基础值)差异未见统计学意义(P>0.05)。七氟烷后处理组和缺血后处理组可改善再灌注损伤心功能的各项指标(P<0.05)。复灌90min,Sevo组和Post组心肌梗死面积显著低于I/R组(P<0.05)。与I/R组比较,Sevo组和Post组胞质细胞色素C的含量明显减少(P<0.05),同时伴随线粒体细胞色素C的含量明显增多(P<0.05)。电子显微镜观察线粒体形态,Sevo组和Post组的损伤程度比I/R组明显减轻。结论七氟烷后处理对大鼠离体心脏再灌注损伤有明显的保护作用,其保护强度与缺血后处理相当,机制可能与减轻线粒体的损伤,抑制细胞色素C的释放有关系。
Aim To investigate the effect of sevoflurane postconditioning on isolated rat hearts with acute myocardial ischemia reperfusion injury. Methods 48 SD rats were randomly divided into 4 groups （ n = 12 ） ： sham（ 150 rain perfusion） ;ischemia reperfusion（30min ischemia） ;4 cycles of ischemia postconditioning （20 s of each） ;2.57 V/V sevoflurane postconditioning （ 1.5 minimum alveolar concentration ）, using Langendorff （apparatus. Except sham group, all groups subjected to 30 rain ischemia followed by 90 rain reperfusion. Post group was subjected to 4 cycles of 20 s reperfusion/ischemia after 30 min ischemia; 10 min of washout was administered immediately after Sevo group was induced by 5 min 2. 57 vol % sevoflurane at onset of reperfusion. Recording Left ventricular diastolic pressure （ LV- EDP） , Left ventricular developed pressure （ LVDP ） , Heart rate （HR）, Coronary flow （CF）, ＋ dp/dt and - dp/dt at 30 rain of equilibrium, 30,60,90 rain of reperfusion respectively. Acute infarct size was measured using 1% triphenyltetrazolium chloride staining.Configuration of mitochondria was observed by electronmicroscope. Western blot analysis was used to determine contents of cytosolic and mitochondrial cytochrome C at the end of reperfusion. Results No differences in baseline hemodynamics were observed among the experimental groups （ P 〉 0. 05 ）. After reperfusion, Sevo group and Post group resulted in a significant increase （P 〈 0. 05 ） in hemodynamics compared with I/ R group. Sevo group and Post group significantly （P 〈 0. 05） reduced infarct size（21% ＋/- 7% ,23% ＋/ - 6%, respectively） VS I/R group （ 39% ＋ / - 9% ）. Sevo group and Post group improved configuration of mitochodria and significantly （ P 〈 0. 05 ） reduced the release of cytochrome C from mitochodria into cytosol- ic. Conclusion Sevoflurance postconditioning effec- tively protects against reperfusion damage similar to ischemia postconditionding. The mechanism might be involved in decreasing the damage of mitochodria.
出处
《中国药理学通报》
CAS
CSCD
北大核心
2008年第6期766-771,共6页
Chinese Pharmacological Bulletin
基金
江苏省卫生厅开放课题(NoKJS200603)
关键词
七氟烷
后处理
缺血/再灌注损伤
线粒体
细胞色素C
sevoflurance
postconditioning
ischemia-reperfusion damage
mitochodria
cytochrome C
