复心汤对大鼠原代心肌细胞IP3-Ca~(2+)/CaM-CaN通路的影响Effects of Fuxin Decotion on the Expression of IP3-Ca~(2+)/CaM-CaN Pathway in the Generation of Rat Myocardial Cells
薛一涛,陈瑞雪,高翔宇,孙德,焦华琛
摘要(Abstract):
目的研究用复心汤含药血清培养的大鼠原代心肌细胞中IP3-Ca~(2+)/CaM-CaN通路的表达情况,并与缬沙坦干预后的心肌细胞模型进行比较,观察复心汤对心肌细胞的干预效果,进一步探讨复心汤抗心衰的作用靶点及机制,为临床及科研提供一条新思路。方法健康成年的雄性Wistar大鼠50只,随机分为空白对照组、复心汤低剂量组、复心汤中剂量、复心汤高剂量组、西药(缬沙坦)组,分别给予生理盐水,低、中、高剂量复心汤及缬沙坦每天1次灌胃1周,末次灌胃后腹主动脉采血并分离血清,血清经灭活、滤菌。含药血清干预原代心肌细胞后分别采用Elisa、激光共聚焦成像技术、Western blot法检测心肌中IP3、Ca~(2+)、CaM及CaN的表达情况及或定量分析。结果复心汤高剂量组及西药组IP3表达量较空白组明显降低,有显著统计学意义(P<0.01);复心汤中、高剂量及西药组CaM、CaN表达量明显降低,差异有统计学意义(P<0.01或P<0.05);与西药组相比,复心汤高剂量组IP3、CaM、CaN表达量差异无显著统计学意义(P>0.05);Ca~(2+)荧光探针荧光强度由高到低依次是空白组,复心汤低、中、高剂量组,西药组。表明高剂量复心汤治疗心衰的效果与缬沙坦相当。结论复心汤治疗心衰可能与IP3-Ca~(2+)/CaM-CaN通路有关。
关键词(KeyWords): 复心汤;心衰;IP3;Ca2~(+);CaM;CaN
基金项目(Foundation): 国家自然科学基金项目(81273703)
作者(Author): 薛一涛,陈瑞雪,高翔宇,孙德,焦华琛
参考文献(References):
- [1]中华医学会心血管病学分会,中华心血管病杂志编辑委员会.慢性心力衰竭诊断治疗指南[J].中华心血管杂志,2007,12(35):1076-1095.
- [2]戴闺柱.慢性心力衰竭治疗的现代概念[J].中华心血管病杂志,2000,2(1):75-78.
- [3]Clapham DE,Sneyd J.Intracellular calcium waves[J].Adv Second Messenger Phosphoprotein Res,1995,30:1-24.
- [4]Honda Z,Nakamura M,Miki I,et al.Cloning by functional expression of platelet activating factor receptor from guineapig lung[J].Nature,1991,349(6307):342-346.
- [5]古雅丽,石四箴.细胞内离子分析[J].同济大学学报:医学版,2001,22(6):54-56.
- [6]Hongo K,White E,Gannier F,et al.Effect of stretch on contraction and the transient ferret ventricular muscles during hypoxia and acidosis[J].Am J Physiol,1995,269∶C690-697.
- [7]Bers DM,Guo T.Calcium signaling in cardiac ventricular myocytes[J].Ann N Y Acad Sci,2005,1047:86-98.
- [8]Maier LS,Bers DM.Calcium,calmodulin,and calciumcalmodulin kinaseⅡ:heartbeat to heartbeat and beyond[J].J Mol Cell.
- [9]Schulz RA,Yutzey KE.Calcineurin signaling and NFAT activation in cardiovascular and skeletal muscle development[J].Dev Bio,2004(1):1-16.
- [10]Xiaomei S,Juyan Z,Bei C.Construction of rat calcineurin A-c DNA recomb inant adenovirus vector and its identification[J].J Huazhong University Sci Technol,2006,26(1):9-12.
- [11]Karatas A,Hegner B,de Windt LJ,et al.Deoxycorticosterone acetate-saltmice exhibit blood pressure-independent sexual dimorphism[J].Hypertension,2008,51:1177-1183.
- [12]Shiroshita-Takeshita A,Brundel BJ,Lavoie J,et al.Prenisone prevents atrial fibrillation promotion by atrial tachycardia remodeling in dogs[J].Cardiovasc Res,2006,69(4):865.
- [13]Hongo K,White E,Gannier F,et al.Effect of stretch on contraction and the transient ferret ventricular muscles during hypoxia and acidosis[J].Am J Physiol,1995,269∶690-697.
- [14]Schulz RA,Yutzey KE.Calcineurin signaling and NFAT activation in cardiovascular and skeletal muscle development[J].Dev Bio,2004(1):1-16.
- [15]Shiroshita-Takeshita A,Brundel BJ,Lavoie J,et al.Prenisone prevents atrial fibrillation promotion by atrial tachycardia remodeling in dogs[J].Cardiovasc Res,2006,69(4):865.