CaMKⅡ信号通路在黄芪多糖抑制异丙肾上腺素诱导心肌细胞肥大中的作用  

Effects of CaMKⅡ signaling pathway on astragalus polysaccharides inhibition of isoproterenol induced cardiomyocyte hypertrophy in neonatal rats

作　　者：张静[1] 王洪新[1] 杨娟[1] 鲁美丽[1] 李胜陶[1] 喻晓春[2] 

机构地区：[1]辽宁医学院辽宁省心脑血管药物重点实验室,辽宁锦州121001 [2]中国中医科学院实验中心,北京100700

出　　处：《中国药理学通报》2013年第8期1109-1114,共6页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 30973898/C190702);辽宁省自然科学资金项目(No 201102141)

摘　　要：目的从钙调素依赖蛋白激酶Ⅱ(Ca2+/calmodulin-de-pendent protein kinaseⅡ,CaMKⅡ)信号通路角度探讨黄芪多糖(astragalus polysaccharides,APS)对异丙肾上腺素(isoprot-erenol,Iso)诱导心肌细胞肥大的保护作用及机制。方法原代培养大鼠乳鼠心肌细胞,应用Iso 10μmol·L-1诱导心肌细胞肥大,观察β受体阻断剂普萘洛尔及不同浓度APS对肥大心肌细胞的影响。用消化分离法及计算机图像分析系统测细胞体积;Bradford法测心肌细胞总蛋白含量;ELISA法检测细胞外液中IL-6和TNF-α的含量;RT-PCR法检测ANP mRNA的表达;Western blot法检测心肌细胞CaMKⅡδ蛋白的表达。结果普萘洛尔(propranolol,PRO)和APS均能有效抑制Iso诱导的心肌细胞肥大,表现为体积减小、总蛋白含量降低及ANP mRNA表达降低,并能有效减少炎症反应,表现为细胞外液中IL-6、TNF-α的含量明显减少,CaMKⅡδ蛋白含量减少,且APS的作用呈一定的剂量依赖性。结论黄芪多糖对Iso诱导的乳鼠心肌细胞肥大具有保护作用,其机制可能与抑制CaMKⅡ信号通路及减少炎症反应有关。Aim To investigate the inhibitive effects of astragalus （Foundation item： the project supported by National Natural Science Foundation of China （30973898/C190702） ） polysaccharides （APS） on hypertrophic myocardial cells induced by isoproterenol （Iso） through CaMK II signal pathway in neonatal rats. Methods The primary cultures of neonatal rat ventricular myocytes were used. The hypertrophic cardiac myocytes were induced by Iso 10 μmol · L-1 ,and the effect of propranolol, a β-adrenoceptor antagonist and different concentrations of APS on cardiac hypertrophy were observed. The cardiomyocytes volume was measured by computer photograph analysis system. Total protein content was assayed by the method of Brad- ford. The expression of IL-6 and TNF-α were determined by ELISA. The expression of ANP mRNA was determined by RT-PCR,and the expression of CaMK H 8 was measured by Western blot. Result Propranolol and APS were able to inhibit the Iso-induced cardiac hypertrophy, expressed as the decreased volume, pro- tein content and the expression of ANP mRNA. APS could abolish the inflammatory response induced by Iso, expressed as the decreased expression of IL-6, TNF-α and the expression of CaMK H 8. APS had a dose-dependent inhibitory effect. Conclusions APS has a protective effect on Iso induced cardiac hypertrophy, which is partially via attenuating inflammatory effect and the expression of CaMK II induced by Iso.

关 键 词：黄芪多糖 异丙肾上腺素 心肌细胞 CaMKⅡ炎症 保护作用 

分 类 号：R332[医药卫生—人体生理学] R284.1[医药卫生—基础医学]