去铁胺预处理联合七氟醚后处理对糖尿病大鼠心肌缺血再灌注损伤的影响

Effects of deferoxamine pretreatment combined with sevoflurane postconditioning on myocardial ischemia-reperfusion injury in diabetic rats

目的:探讨去铁胺(DFO)预处理联合七氟醚后处理(SPostC)对糖尿病大鼠心肌缺血再灌注(I/R)损伤的影响。方法:采用Langendorff离体灌流装置建立I/R模型,缺血40 min,再灌注2 h。通过给予DFO预处理和(或)SPostC,观察各组再灌注末的心率、左室发展压(LVDP)、左室舒张末期压力(LVEDP)及左室内压最大上升速率(+dp/dtmax)等血流动力学指标的变化,Western blot法测定心肌缺氧诱导因子-1α(HIF-1α)、血管内皮生长因子(VEGF)的表达水平变化,电镜观察心肌线粒体超微结构,TTC染色法测定心肌梗死面积。结果:与对照组相比,其余各组心率、LVDP、+dp/dtmax均明显降低,LVEDP和心肌梗死面积均明显增加,HIF-1α、VEGF表达水平均明显上调(P均<0.05),线粒体结构有不同程度的破坏。与I/R组相比,DFO组、DFO+SPostC组LVEDP均明显降低,心率、LVDP、+dp/dtmax均明显改善,HIF-1α、VEGF表达水平均明显上调,心肌梗死面积均明显减少(P均<0.05),线粒体结构完整度明显改善。与DFO组相比,DFO+SPostC组LVEDP明显降低,心率、LVDP、+dp/dtmax明显改善,HIF-1α、VEGF表达上调,心肌梗死面积减少(P均<0.05),线粒体结构基本完整,略有肿胀。结论:DFO预处理联合SPostC可以减轻糖尿病大鼠心肌I/R损伤。

Objective:To investigate the effects of deferoxamine pretreatment combined with sevoflurane postconditioning on myocardial ischemia-reperfusion injury(I/R) in diabetic rats. Methods:The I/R mode was established by using Langendorff perfusion apparatus and the rats were subjected to ischemia for 40 min followed by reperfusion for two hours. After deferoxamine pretreatment and/or sevoflurane postconditioning, hemodynamic parameters such as heart rate(HR), left ventricular development pressure(LVDP), left ventricular end-diastolic pressure(LVEDP), and maximal rate of increase of left ventricular pressure(+dp/dtmax) were recorded in each group. The expression levels of hypoxia-inducible factor(HIF)-1α and vascular endothelial growth factor(VEGF) were determined by western blot. The ultrastructure of mitochondria was observed by electron microscope. The area of myocardial infarction was determined by TTC staining method. Results:Compared with the control group, HR, LVDP and +dp/dtmax in other groups were significantly decreased, and LVEDP and the area of myocardial infarction were significantly increased(P all <0.05). The expression of HIF-1α and VEGF was up-regulated and mitochondrial structure had different degrees of damage(P all <0.05). Compared with I/R group, in the DFO group and DFO+SPostC group, LVEDP was significantly decreased; HR, LVDP and+dp/dtmax were significantly improved; the expression of HIF-1α and VEGF was up-regulated, and the area of myocardial infarction decreased(P all <0.05). The structure of mitochondria was relatively completed in the DFO group and DFO+SPostC group. As compared with DFO group, LVEDP was significantly decreased and HR, LVDP as well as+dp/dtmax were significantly improved; the expression of HIF-1α and VEGF was up-regulated, and the myocardial infarcttion size decreased in the DFO+SPostC group(P all <0.05). The mitochondria structure was almost complete and slightly swollen in DFO+SPostC group. Conclusions:Deferoxamine pretreatment combined with sevoflurane postconditioning can alleviate myocardial IR injury in diabetic rats.