κ受体激动剂对异丙肾上腺素诱导大鼠乳鼠心肌肥厚的作用机制研究  

Study on mechanisms of κ-opioid receptor agonist affects neonatal rat myocardial hypertrophy induced by isoproterenol

作　　者：崔蕾[1] 王洪新[1] 赵敏[1] 

机构地区：[1]辽宁医学院药理学教研室

出　　处：《中国临床药理学与治疗学》2007年第9期1042-1046,共5页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：辽宁省自然科学基金项目(20042170)

摘　　要：目的:利用体外培养的大鼠乳鼠心肌细胞,研究异丙肾上腺素(ISO)诱导肥大心肌细胞中κ阿片受体(κ-OR)的作用及其机制。方法:新生大鼠心肌细胞培养,Lowry’s法测心肌细胞的蛋白含量;用消化分离法,利用计算机图像分析系统测心肌细胞的体积;[3H]leucine掺入法测定心肌细胞蛋白的合成,Western blot法测细胞外信号调节激酶(ERK)磷酸化水平。结果:在给予ISO诱导心肌肥大的情况下,ERK通路抑制剂U0126可减少肥大心肌细胞的蛋白质含量、体积、蛋白合成和ERK磷酸化程度;κ-OR激动剂U50,488H(U50)能够减少肥大心肌细胞的蛋白含量、体积和蛋白合成,但与U0126共同作用时(U0126先孵育30min),其抑制心肌肥大作用一定程度上减小。结论:ISO激活引起ERK磷酸化增加,抑制ERK可以阻断ISO的致肥大作用;κ-OR激活能够抑制ISO所诱导的心肌细胞肥大,其作用机制与ERK相关。AIM：To study the mechanisms of effects of the κ-opioid receptor（κ-OR） on neonatal rat hypertrophic myocardial cells induced by isoproterenol（ISO）.METHODS：Myocardial cells of neonatal rats were cultured in vitro.The total protein content was detected by the Lowry＇s assay.The volume of myocardial cell was measured by computer photogragh analysis system and the protein synthesis was assayed with[^3H] leucine intake method.The degree of extracellular signal-regulated kinase（ERK） phosphorylation was determined by western-blotting.RESULTS：U0126（an inhibitor of ERK） decreased the total protein content,the cell size,the[^3H]leucine incorporation and the ERK phosphorylation degree in hypertrophic myocardial cells induced by ISO.1 μmol/L U50,488H（a κ-opioid receptor antagonist） could decrease the total protein content,the cell size,the[^3H]leucine incorporation and the degree of ERK phosphorylation.But these effects could be diminished when incubated with U0126.CONCLUSION：κ-opioid can abolish the hypertrophic response induced by ISO of cardiac myocytes,which was associate with ERK pathway.The inhibitor of ERK significantly inhibits the ISO-induced hypertrophied effect.

关 键 词：Κ-阿片受体 Β受体 心肌肥大 细胞外信号调节激酶 

分 类 号：R965.2[医药卫生—药理学]