|本期目录/Table of Contents|

[1]杨龙 戴晓雯 马宁 吴建江 王江 郑宏.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[J].国际心血管病杂志,2019,06:358-362.
 YANG Long,DAI Xiaowen,MA Ning,et al.Effects of deferoxamine pretreatment combined with sevoflurane postconditioning on myocardial ischemia-reperfusion injury in diabetic rats[J].International Journal of Cardiovascular Disease,2019,06:358-362.
点击复制

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(PDF)

《国际心血管病杂志》[ISSN:1006-6977/CN:61-1281/TN]

期数:
2019年06期
页码:
358-362
栏目:
基础研究
出版日期:
2019-12-31

文章信息/Info

Title:
Effects of deferoxamine pretreatment combined with sevoflurane postconditioning on myocardial ischemia-reperfusion injury in diabetic rats
作者:
杨龙 戴晓雯 马宁 吴建江 王江 郑宏
830054 乌鲁木齐,新疆医科大学第一附属医院麻醉科
Author(s):
YANG Long DAI Xiaowen MA Ning WU Jianjiang WANG Jiang ZHENG Hong
Department of Anesthesiology, First Affiliated Hospital of Xinjiang Medical University, Xinjiang 830054, China
关键词:
糖尿病 七氟醚后处理 缺血再灌注损伤 缺氧诱导因子-1α
Keywords:
Diabetes Sevoflurane postconditioning Ischemia-reperfusion injury Hypoxia-inducible factor-1α
分类号:
-
DOI:
10.3969/j.issn.1673-6583.2019.06.009
文献标识码:
-
摘要:
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。
Abstract:
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.

参考文献/References

[ 1 ] Preis SR, Pencina MJ, Hwang SJ, et al. Trends in cardiovascular disease risk factors in individuals with and without diabetes mellitus in the framingham heart study[J]. Circulation, 2009, 120(3):212-220.
[ 2 ] Wu J, Yu J, Xie P, et al. Sevoflurane postconditioning protects the myocardium against ischemia/reperfusion injury via activation of the JAK2-STAT3 pathway [J]. Peer J, 2017, 5:e3196
[ 3 ] Yu J, Wu J, Xie P, et al. Sevoflurane postconditioning attenuates cardiomyocyte hypoxia/reoxygenation injury via restoring mitochondrial morphology[J]. Peer J, 2016, 4:e2659.
[ 4 ] Drenger B, Ostrovsky IA, Barak M, et al. Diabetes blockade of sevoflurane postconditioning is not restored by insulin in the rat heart[J]. Anesthesiology, 2011, 114(6):1364-1372.
[ 5 ] Yang L, Xie P, Wu JJ, et al. Sevoflurane postconditioning improves myocardial mitochondrial respiratory function and reduces myocardial ischemia-reperfusion injury by up-regulating HIF-1[J]. Am J Transl Res, 2016, 8(10):4415-4424.
[ 6 ] Thangarajah H, Vial IN, Grogan RH, et al. HIF-1 alpha dysfunction in diabetes[J]. Cell Cycle, 2010, 9(1):75-79.
[ 7 ] Bento CF, Pereira P. Regulation of hypoxia-inducible factor 1 and the loss of the cellular response to hypoxia in diabetes[J]. Diabetologia, 2011, 54(8):1946-1956.
[ 8 ] Eckle T, Köhler D, Lehmann R, et al. Hypoxia-inducible factor-1 is central to cardioprotection: a new paradigm for ischemic preconditioning[J]. Circulation, 2008, 118(2):166-175.
[ 9 ] Duscher D, Neofytou E, Wong VW, et al. Transdermal deferoxamine prevents pressure-induced diabetic ulcers[J]. Proc Natl Acad Sci U S A, 2015, 112(1):94-99.
[10] Marfella R, D'Amico M, Di Filippo C, et al. Myocardial infarction in diabetic rats: role of hyperglycaemia on infarct size and early expression of hypoxia-inducible factor 1[J]. Diabetologia, 2002, 45(8):1172-1181.
[11] Luciano JA, Tan T, Zhang Q, et al. Hypoxia inducible factor-1 improves the actions of nitric oxide and natriuretic peptides after simulated ischemia-reperfusion[J]. Cell Physiol Biochem, 2008, 21(5/6):421-428.
[12] Zhang L, Luo X, Chen F, et al. LncRNA SNHG1 regulates cerebrovascular pathologies as a competing endogenous RNA through HIF-1α/VEGF signaling in ischemic stroke[J]. J Cell Biochem, 2018, 119(7):5460-5472.
[13] Zhang W, Xiong Z, Wei T, et al. Nuclear factor 90 promotes angiogenesis by regulating HIF-1α/VEGF-A expression through the PI3K/Akt signaling pathway in human cervical cancer [J]. Cell Death Dis, 2018, 9(3):276.
[14] Fu SP, He SY, Xu B, et al. Acupuncture promotes angiogenesis after myocardial ischemia through H3K9 acetylation regulation at VEGF gene[J]. PLoS One, 2014, 9(4):e94604.
[15] Ashina K, Tsubosaka Y, Kobayashi K, et al. VEGF-induced blood flow increase causes vascular hyper-permeability in vivo[J]. Biochem Biophys Res Commun, 2015, 464(2):590-595.

备注/Memo

备注/Memo:
基金项目:新疆维吾尔自治区自然科学基金(2017D01C340)
作者单位:830054 乌鲁木齐,新疆医科大学第一附属医院麻醉科
通信作者:郑宏,Email:xjzhenghong@aliyun.com
更新日期/Last Update: 2019-12-27