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张彤,吴波,焦华琛,刘元峰,戴国华.补肾活血中药激活MMP-9信号通路动员大鼠骨髓EPCs的分子机制研究[J].中国中西医结合杂志,2013,33(6):0795-0799
补肾活血中药激活MMP-9信号通路动员大鼠骨髓EPCs的分子机制研究
Chinese Herbs for Shen Invigorating and Blood Activating Activated MMP-9 Signaling Pathway to Mobilize Rats′ Bone Marrow EPCs: a Molecular Mechanism Research
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DOI:10.7661/CJIM.2013.06.0795
中文关键词:  心肌梗死模型大鼠  内皮祖细胞  补肾活血中药  基质金属蛋白酶9信号通路
英文关键词:myocardial infarction model rat  endothelial progenitor cell  Chinese herbs for Shen invigorating and blood activating  MMP-9 signaling pathway
基金项目:山东省自然科学基金资助项目(NoZR2009CL034);国家自然科学基金面上项目(No81173441)
作者单位E-mail
张彤,吴波,焦华琛,刘元峰   
戴国华 山东中医药大学附属医院心内科(济南250011) daigh2004@163.com 
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中文摘要:
      目的探讨补肾活血中药对心肌梗死(myocardial infarction,MI)模型大鼠骨髓、外周血内皮祖细胞(endothelial progenitor cells,EPCs)数量及骨髓基质金属蛋白酶9(matrix metalloproteinase 9,MMP-9)信号通路的影响。方法结扎法建立大鼠MI模型,30只造模成功大鼠随机分为补肾活血中药高剂量组、补肾活血中药低剂量组和模型组,每组10只,另取10只正常大鼠为空白组。补肾活血中药高、低剂量组分别用补肾活血中药按3 g/kg、1.5 g/kg加生理盐水4 mL灌胃,每天1次。空白组及模型组每天单用生理盐水4 mL灌胃1次。4周后骨髓、外周血EPC培养,7天后收集贴壁细胞运用流式细胞仪鉴定CD34/CD133表型,Western blot法检测MMP-9和水溶性Kit配体(solouble Kit ligand,sKitL),ELISA法检测血管内皮生长因子(vascular endothelial growth factor,VEGF)和基质细胞衍生因子-1α(stromal cell-derived factor-1α,SDF-1α)。结果补肾活血中药高、低剂量组骨髓和外周血表达CD34/CD133阳性率、EPC数量均高于模型组(P<0.05,P<0.01);且两组骨髓和外周血VEGF、SDF-1α、MMP-9和sKitL表达均高于模型组(P<0.05,P<0.01)。结论补肾活血中药能够激活MMP-9信号通路,增加其上游和下游信号表达水平,动员骨髓EPC进入血液循环。
英文摘要:
      ObjectiveTo explore the effect of Chinese herbs for Shen invigorating and blood activating (CHSIBA) on the number of endothelial progenitor cells (EPCs) in the bone marrow and the peripheral blood and the signaling pathway of bone marrow matrix metalloproteinase 9 (MMP-9) of the myocardial infarction (MI) model rats. MethodsThe MI rat model was established by ligation. Thirty successfully modeled rats were randomly divided into the high dose CHSIBA group, the low dose CHSIBA group, and the model group, 10 in each group. Besides, another 10 normal rats were recruited as the blank group. Rats in the high dose CHSIBA group and the low dose CHSIBA group were administered with CHSIBA at 3 g/kg and 1.5 g/kg body weight by gastrogavage (by adding them in 4 mL physiological saline), once daily. Rats in the model group and the blank group were administered with 4 mL physiological saline once daily. The EPCs were collected from the bone marrow and the peripheral blood 4 weeks later. Seven days later the CD34/CD133 phenotype was identified in collected sticking wall cells using flow cytometry. The MMP-9 and water soluble Kit ligand (sKitL) were detected using Western blot. The expressions of vascular endothelial growth factor (VEGF) and stromal cell-derived factor-1α (SDF-1α) were detected using ELISA. ResultsThe CD34/CD133 positive rate and the EPC quantity in the bone marrow and the peripheral blood were higher in the high dose CHSIBA group and the low dose CHSIBA group than in the model group (P<0.05, P<0.01). Besides, the expressions of VEGF, SDF-1α, MMP-9, and sKitL in the bone marrow and the peripheral blood were also higher in the high dose CHSIBA group and the low dose CHSIBA group than in the model group (P<0.05, P<0.01). ConclusionCHSIBA could activate MMP-9 signaling pathway, increase its upstream and downstream signal expression levels, and mobilize EPCs in the bone marrow to enter the blood circulation.
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