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

中国临床药理学与治疗学 ›› 2007, Vol. 12 ›› Issue (9): 1042-1046.

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

崔蕾, 王洪新, 赵敏

辽宁医学院药理学教研室, 锦州121000, 辽宁

收稿日期:2007-05-29 修回日期:2007-07-09 出版日期:2007-09-26 发布日期:2020-10-30
通讯作者: 王洪新, 男, 医学博士, 教授, 主要从事心血管药理学研究。Tel:13304169343 E-mail:Jyhxwang@163.com
作者简介:崔蕾, 女, 硕士, 主要从事心血管药理学研究。E-mail:leilei_0_cn1@yahoo.com.cn
基金资助:
辽宁省自然科学基金项目(20042170)

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

CUI Lei, WANG Hong-xin, ZHAO Min

Department of Pharmacology, Liaoning Medical College, Jinzhou 121000, Liaoning, China

Received:2007-05-29 Revised:2007-07-09 Online:2007-09-26 Published:2020-10-30

摘要/Abstract

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30 min), 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。

关键词: κ-阿片受体, β 受体, 心肌肥大, 细胞外信号调节激酶

Abstract: 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.

Key words: κ-opioid, β-receptor, myocardial hypertrophy, extracellular signal-regulated kinase

中图分类号:

R965.2

崔蕾, 王洪新, 赵敏. 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[J]. 中国临床药理学与治疗学, 2007, 12(9): 1042-1046.

CUI Lei, WANG Hong-xin, ZHAO Min. Study on mechanisms of κ-opioid receptor agonist affects neonatal rat myocardial hypertrophy induced by isoproterenol[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2007, 12(9): 1042-1046.

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