吗啡对血清饥饿致培养乳大鼠心肌细胞凋亡的影响及机制  

Effect of morphine on serum hungry-induced apoptosis in cardiac myocytes

作　　者：唐博[1] 王洪新[1] 王大鹏[1] 喻晓春[2] 

机构地区：[1]辽宁医学院药理学教研室,辽宁锦州121000 [2]中国中医科学院实验中心,北京100700

出　　处：《中国药理学通报》2008年第8期1035-1040,共6页Chinese Pharmacological Bulletin

基　　金：辽宁省自然科学基金资助项目(No20042170)

摘　　要：目的利用体外原代培养的乳大鼠心肌细胞,研究吗啡对血清饥饿诱导心肌细胞凋亡的影响及其机制。方法体外原代培养乳大鼠心肌细胞,各组分别给药作用48h后,用MTT法测心肌细胞的活力;用Annexin V-FITC/PI双标记法测心肌细胞的凋亡率;用流式细胞仪分析心肌细胞周期;用Westernblot法测PKC和Caspase-3蛋白的表达。结果体外原代培养的乳大鼠心肌细胞经无血清饥饿作用48h后,心肌细胞可出现明显的凋亡现象;给予1μmol·L-1吗啡作用于心肌细胞后,心肌细胞的这种凋亡现象可明显被抑制,表现为:心肌细胞凋亡率降低、Caspase-3蛋白表达减少;但吗啡的这种抑制心肌细胞凋亡作用可被10μmol·L-1 naloxone完全阻断;并且给予10μmol·L-1GF109203X或1μmol·L-1Staurosporine与吗啡共同作用时,吗啡抑制心肌细胞凋亡的作用亦在一定程度上降低,表现为:心肌细胞凋亡率增加、Caspase-3蛋白表达增加、PKC蛋白表达减少。结论吗啡可激活心肌细胞膜上的阿片受体,通过PKC途径对血清饥饿诱导的心肌细胞凋亡具有抑制作用。Aim Myocardial cells of neonatal rats were cultured in vitro to study aim of morphine on serum hungry-induced apoptosis mechanism. Methods in cardiac myocytes and its Myocardial ceils of neonatal rats were cultured in vitro. 48 hours later, different a- gents were added to cardiac myocytes. The cellular sur- vival was determined with MTI＂ colormeteric assay; ap- optosis rates were determined by Annexin V-FITC/PI; cell cycle was determined by flow cytometry;Caspase-3 and PKC were investigated by Western blot. Results Free-serum induced apoptosis in cardiac myocytes was shown after 48 hours ; morphine （ 1μmol·L-1） could inhibit apoptosis in cardiac myocytes, manifestation, ap- optosis rates were decreased, Caspase-3 experssion was decaeased Naloxone at 10 μmol·L-1 inhibited the promoting effects of morphine;GF109203X at 10 μmol·L-1 or Staurosporine at 1 μmol·L-1 could inhibit the promoting effects of morphine, manifestation, apoptosis rates were increased, Caspase-3 experssion was in- caeased, PKC expression was decreased. Conclusion morphine inhibited serum hungry-induced apoptosis in cardiac myocytes via PKC signal transduction pathway.

关 键 词：吗啡 阿片受体 心肌细胞 凋亡 Caspase-3 PKC 

分 类 号：R-332[医药卫生] R322.11