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张大武,张蕾,刘剑刚,王承龙,史大卓,陈可冀.芎芍胶囊联合缺血后适应对大鼠缺血/再灌注心肌MCP-1及TNF-α的影响[J].中国中西医结合杂志,2010,30(12):1279-1283
芎芍胶囊联合缺血后适应对大鼠缺血/再灌注心肌MCP-1及TNF-α的影响
Effects of Xiongshao Capsule Combined with Ischemic Postconditioning on Monocyte Chemoattractant Protein-1 and Tumor Necrosis Factor-α in Rat Myocardium with Ischemic Reperfusion Injury
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DOI:
中文关键词:  芎芍胶囊  再灌注损伤  缺血后适应  炎症
英文关键词:Xiongshao Capsule  reperfusion injury  ischemic postconditioning  inflammation
基金项目:国家自然科学基金资助项目(No.30973969);国家“十一五”科技支撑计划资助项目(No.2006BAI04A01-2);国家“重大新药创制”科技重大专项(No.2009ZX09502-031)
作者单位
张大武 中国中医科学院西苑医院心血管病中心 
张蕾 中国中医科学院西苑医院心血管病中心 
刘剑刚 中国中医科学院西苑医院心血管病中心 
王承龙 中国中医科学院西苑医院心血管病中心 
史大卓 中国中医科学院西苑医院心血管病中心 
陈可冀 中国中医科学院西苑医院心血管病中心 
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中文摘要:
      目的观察芎芍胶囊(Xiongshao Capsule,XSC)联合缺血后适应(ischemic postconditioning,IPoC)对大鼠缺血/再灌注(ischemic reperfusion,I/R)损伤心肌单核细胞趋化蛋白-1(monocyte chemoattractant protein-1,MCP-1)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)含量及炎性细胞浸润的影响。方法 Spragu-Dawley(SD)大鼠75只,随机分为假手术组、I/R组、IPoC组、福辛普利钠加IPoC组、XSC加IPoC组,每组15只。除假手术组外,其他各组均结扎大鼠冠状动脉前降支30min,再灌注1h。IPoC组大鼠在再灌注1h前予以3次10s的再灌注/缺血循环,福辛普利钠加IPoC组和XSC加IPoC组分别给予福辛普利钠0.9mg/kg和芎芍胶囊0.135g/kg,连续灌胃14天,末次灌胃2h后实施手术取材。采用比色法测定血清肌酸激酶同工酶(creatine kinase-MB,CK-MB)和肌钙蛋白T(cardiac troponin T,cTnT)的含量,氯化硝基四氮唑兰(nitro blue tetrazolium chloride,NBT)染色测定大鼠左室心肌梗死面积,酶联免疫吸附测定法(enzyme-linked immunosorbant assay,ELISA)测定心肌组织MCP-1和TNF-α含量,HE染色观察心肌组织炎性细胞的浸润。结果与I/R组比较,IPoC组大鼠血清CK-MB和cTNT水平明显降低(P<0.01),心肌梗死面积显著减小(P<0.01),心肌组织MCP-1、TNF-α含量和炎性细胞浸润明显下降(P<0.05,P<0.01);与IPoC组比较,XSC加IPoC进一步降低了I/R大鼠心肌梗死面积和CK-MB含量(P<0.01),大鼠心肌MCP-1、TNF-α含量和炎性细胞浸润数量显著降低(P<0.05,P<0.01)。结论芎芍胶囊可加强缺血后适应对I/R大鼠心肌的保护作用,其机制可能与抑制MCP-1、TNF-α表达和炎性细胞浸润有关。
英文摘要:
      Objective To investigate effect of Xiongshao Capsule (XSC) combined with ischemic postconditioning (IPoC) on tumor necrosis factor-α (TNF-α) and monocyte chemoattractant protein-1 (MCP-1) contents as well as inflammatory cell infiltration (ICI) in myocardium of rat with ischemic reperfusion (I/R) injury.Methods Seventy-five Sprague-Dawley rats were equally randomized into 5 groups,the sham-operated group (A),the I/R group (B),the IPoC group (C),the fosinopril sodium plus IPoC group (D),and the XSC plus IPoC group (E).Excepting rats in Group A,all animals received I/R injury through a 30-min occlusion of left anterior descending artery followed by 1-h reperfusion.Additionally,IPoC (3 cycles of 10s reperfusion/10s of ischemia) was applied on rats in Group C before 1h of reperfusion;while rats in Groups D and E were pretreated for 14 days with 0.9mg/kg fosinopril sodium and 0.135g/kg XSC respectively via gastrogavage,and the I/R injury with IPoC applied 2h after the final gavage.Serum creatine kinase-MB (CK-MB) and cardiac troponin T (cTnT) levels were detected by colorimetric method,myocardial infarction size was measured by nitro blue tetrazolium chloride (NBT) staining,MCP-1 and TNF-α contents in myocardial tissue were examined by enzyme-linked immunosorbent assay (ELISA),and ICI was detected by HE staining.Results Compared with Group B,myocardial enzymes and infarction size were significantly decreased (P<0.01),contents of MCP-1,TNF-α and ICI in myocardial tissue were significantly decreased (P<0.05,P<0.01) in Group C.Compared with Group C,further reduced infarction size and release of myocardial enzyme CK-MB (P<0.01) were seen in Group E,and contents of MCP-1 and TNF-α as well as ICI in myocardial tissue in Group E were also significantly lower (P<0.05,P<0.01).Conclusion XSC could enhance the protective effect of IPoC on rat with myocardial I/R injury,and the mechanism may be related to its inhibition on MCP-1 and TNF-α expressions as well as ICI suppression.
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