芪丹通脉片对心肌梗死大鼠缺血心肌血管新生及HIF-1α、VEGF表达的影响Effe ct of Qidantongmai Tablet on Angiogenesis and Expression of HIF -1α and VEGF in Ischemic Myocardium of Rats with Myocardial Infarction
衣慧,王俊超,司静文,张玉芬,王宗仁,李军昌
摘要(Abstract):
目的观察芪丹通脉片(QDTMT)对心肌梗死后气虚血瘀证大鼠缺血心肌血管新生的作用及对HIF-1α、VEGF表达的影响。方法以结扎SD大鼠左冠状动脉前降支,制备急性心肌梗死模型,随机分为假手术(Sham)组、梗死组(MI)组、MI+芪丹通脉片小剂量(MI+QDTMTL)组和MI+芪丹通脉片大剂量(MI+QDTMTH)组。术后24 h各组均用生理盐水配制成等体积药液灌胃,4周后动态评价各组大鼠气虚血瘀表征变化,采用免疫组化染色方法检测梗死边缘区CD31的表达,测定各组大鼠缺血心肌中新生血管数、微血管密度,于第7日、14日及28日时检测心梗边缘区HIF-1α和VEGFmRNA的表达。结果 (1)Sham组无气虚血瘀证相关表现,而MI组、MI+QDTMTL组和MI+QDTMTH组都有气虚血瘀的相关表现,且MI组表现最为明显。(2)MI+QDTMTL组和MI+QDTMTH组CD31的表达较MI组增强,且MI+QDTMTH组高于MI+QDTMTL组。(3)与MI组相比,MI+QDTMTL组和MI+QDTMTH组心梗边缘区新生血管数及微血管密度增加,且MI+QDTMTH组高于MI+QDTMTL组。(4)RT-PCR结果显示,心梗后7 d、14 d时MI+QDTMTL组和MI+QDTMTH组HIF-1αmRNA及VEGF mRNA相对表达量较MI组增高,28 d时MI+QDTMTL组和MI+QDTMTH组HIF-1αmRNA及VEGF mRNA相对表达量较MI组降低。结论 QDTMT能够改善心梗大鼠气虚血瘀的症状,增加心梗边缘区新生血管数和微血管密度,调控HIF-1α与VEGFmRNA的表达,为心梗后心功能的改善提供了新的治疗思路,其机制可能与活化HIF-1α信号调控HIF-1αmRNA及VEGF mRNA的表达有关。
关键词(KeyWords): 芪丹通脉片;气虚血瘀;血管新生;缺氧细胞诱导因子-1α;血管内皮细胞生长因子
基金项目(Foundation): 国家自然科学基金资助项目(81072972)
作者(Author): 衣慧,王俊超,司静文,张玉芬,王宗仁,李军昌
参考文献(References):
- [1]吴焕林,阮新民,杨小波.319例冠心病患者证候分布规律分析[J].中国中西医结合杂志,2007,27(6):498-501.
- [2]何庆勇,王阶,张允岭,等.女性冠心病中医证候学及冠脉病变特点研究[J].中国中西医结合杂志,2009,29(10):879-882.
- [3]杨来宝,温苑,马国超,等.中药早期干预对急性心肌梗死患者心功能的影响[J].山西中医,2012,28(3):11-13.
- [4]Losodo DW,Isner JMl.Gene therap y f o rmyocardial angio-genesis[J].Am Hreat J,1999,138:132.
- [5]陈文元,吴立娅,陈岩,等.中药影响血管新生作用机制研究进展[J].中国中医基础医学杂志,2009,15(3):237-239.
- [6]王宗仁,郑瑾,马爱玲,等.中药芪丹通脉片对动脉粥样硬化大鼠主动脉内皮细胞及PAI-1表达影响[J].第四军医大学学报,2004,25(14):1290-1293.
- [7]李晶华,王宗仁,肖铁卉,等.芪丹通脉片预防异丙肾上腺素所致的大鼠慢性心肌缺血[J].第四军医大学学报,2003,24(5):397-399.
- [8]Jiang BH,Zheng JZ,Leung SW,et al.Transactivation and in-hibitory domains of hypoxia-inducible factor 1 alpha.Modu-lation of transcriptional activity by oxygen tension[J].J BiolChem,1997,272(31):19253-19260.
- [9]Zhao HX,Wang XL,Wang YH,et al.Attenuation of myocar-dial injury by postconditioning:role of hypoxia inducible fac-tor-1α[J].Basic Res Cardiol,2010,105(1):109-118.
- [10]Xie JJ,Liao YL,Yang L,et al.Ultrasound molecular imaging of angiogensis induced by mutant fbrms of hypoxia induced factor-1α[J].Cardiovasc Res,2011,92(2):256-266.
- [11]Kido M,Du L,Sullivan CC,et al.Hypoxia-inducible factor 1alpha reduces infarction and attenuates progession of cardiac dysfunction after myocardial infarction in the mouse[J].J Am Coll Cradiol,2005,46(11):2116-2124.
- [12]Pugh CW,Ratcliffe PJ.Regulation of angiogenesis by hypoxi-a:role of the HIF system[J].Nat Med,2003,9(6):677-684.
- [13]Shohet RV,Garcia JA.Keeping the engine primed:HIF ac-tors as key regulators of cardiac metabolism and angiogenesis during ischemia[J].J Mol Med,2007,85(12):1309-1315.
- [14]Dou GR,Wang YC,Hu XB,et al.RBP-J,the transcription factor downstream of Notch receptors,is essential for the maintenance of vascular homeostasis in adult micel[J].FASEB J,2008,22(5):1606-1617.
- [15]Dong H,Wang Q,Zhang Y,et al.Angiogenesis induced by hVEGF165gene controlled by hypoxic response elements in rabbit ischemia myocardium[J].Exp Biol Med(Maywood),2009,234(12):1417-1424.
- [16]Elson DA,Thurston G,Huang LE,et al.Induction of hyper-vascularity without leakage or inflammation in transgenic mice over expressing hypoxia-inducible factor-1α[J].Genes Dev,2001,15:2520-2532.