中国药理学通报2012,Vol.28Issue(8):1135-1140,6.DOI:10.3969/j.issn.1001-1978.2012.08.022
精胺预处理对离体灌流大鼠心肌缺血/再灌注损伤及细胞凋亡的影响
Effect of spermine preconditioning on myocardial ischemia/reperfusion injury and cardiomyocyte apoptosis in isolated perfused rat heart
摘要
Abstract
Aim To explore the effect of spermine preconditioning on myocardial ischemia/reperfusion injury and its potential antiapoptotic action in isolated perfused rat heart. Methods The model of myocardial is-chemia-reperfusion injury was replicated with Lange-hdorff isolated perfused rat heart. 24 rats were randomly divided into 3 groups: control, IR and spermine, with 8 rats in each group. LDH activity in coronary effluent, SOD activity and MDA content in myocardium were determined with colorimetry. Cardiac performances were monitored on multichannel physiologic recorder. Morphological changes of myocardium were observed by light microscope with HE staining. Myocardial infarction size was measured with TTC staining. Cell apoptosis was detected with transmission electron microscope and TUNEL assay. Fas and Bcl-2 protein expressions were tested with immunohistochemistry. Results (1) Compared with the control group, in IR group, LDH activity in coronary effluent increased distinctly , MDA in myocardial tissues rose, SOD activity decreased (P < 0. 01 ) , and heart function declined obviously(LVDP,HR,CF were all lower than those in the control group, P < 0. 05 ) . Myocardial cells were found to show coagulated zonal necrosis under light microscope. In comparison to the control, in IR group, myocardial infarction size and myocardial cells apoptot- ic rate increased evidently ( P < 0. 05 ) . Fas protein expression was up-regulated while Bcl-2 expression down-regulated. Under transmission electron microscope, myocardium cells displayed chromatin condensation and aggregation at the periphery of the nucleons, with chromatins aggregating like a crescent around nuclear membrane and mitochondria crista disorder. (2) Compared with IR group, in spermine group, LDH activity decreased, MDA content declined, while SOD activity increased (P < 0. 01) , heart function improved greatly (LVDP,HR and CF were all higher than those in IR group, P < 0. 05 ) . Cardiac myocytes showed clear structure under light microscope. In contrast to IR group, in spermine group, myocardial infarction size and cells apoptotic rate decreased evidently ( P < 0. 01 ). Fas protein expression was down-regulated while Bcl-2 expression up-regulated. Electron microscope showed clearly defined sarcomere in myocardium, complete mitochondria crista, dense substrate but no condensation of chromatin. Conclusion Exogenous spermine can greatly decrease the myocardial ischemi-a/reperfusion injury in isolated perfused rat heart and the mechanisms may be related with its antiapoptotic action.关键词
精胺/缺血/再灌注/心脏/坏死/凋亡/Fas/Bcl-2/大鼠Key words
spermine/ ischemia reperfusion/ heart/ necrosis/ apoptosis/ Fas/ Bcl-2 / rat分类
医药卫生引用本文复制引用
赵雅君,张力,王艳丽,杜丽娟,孙智睿,张伟华,王丽娜,薛过,王伟伟,张昊..精胺预处理对离体灌流大鼠心肌缺血/再灌注损伤及细胞凋亡的影响[J].中国药理学通报,2012,28(8):1135-1140,6.基金项目
黑龙江省教育厅课题基金资助(No 11531076) (No 11531076)