M_3受体激动剂毛果芸香碱对离体大鼠心肌缺血再灌注损伤的保护作用  

Protective Effects of M_3 Receptor Agonist Pilocarpine on Myocardial Ischemia-Reperfusion Injury in Isolated Rat Hearts

作　　者：李丹露[1] 刘艳[1] 王丽艳[1] 单宏丽[1] 吕延杰[1] 杨宝峰[1] 

机构地区：[1]哈尔滨医科大学药学院药理教研室,哈尔滨150086

出　　处：《中国药学杂志》2007年第19期1473-1476,共4页Chinese Pharmaceutical Journal

基　　金：黑龙江省卫生厅资助项目(2004-189);黑龙江省青年科学技术专项资金(QC05080);国家自然基金重点项目(30430780);973专项(2004CCAO6700)

摘　　要：目的研究M3受体激动剂毛果芸香碱对离体大鼠心肌缺血再灌注损伤的保护作用。方法采用Langendorff灌注系统,建立离体大鼠心肌缺血再灌注损伤模型。观察毛果芸香碱5μmol.L-1对复灌后冠脉流量、心肌丙二醛(MDA)含量、心肌超氧化物歧化酶(SOD)活性和心肌梗死面积的影响。结果毛果芸香碱改善缺血再灌注后的冠脉流量,其中5 min(P<0.01)和10min(P<0.05)的冠脉流量增加显著;降低心肌MDA含量(P<0.05)并提高心肌SOD活性(P<0.05);缩小心肌梗死面积(P<0.05)。上述作用可被选择性M3受体阻断剂4-diphenylacetoxy-N-methylpiperidine-methiodide(4-DAMP)3 nmol.L-1所逆转。结论M3受体激动剂毛果芸香碱通过激动心肌M3受体而对离体大鼠心肌缺血再灌注损伤起保护作用。OBJECTIVE To investigate the protective effects of M3 receptor agonist pilocarpine on myocardial ischemia-reperfusion injury in isolated rat hearts. METHODS The models of myocardial ischemia-reperfusion injury in isolated rat hearts were built by mounting the isolated rat hearts to Langendorff perfiJsion apparatus and making them ischemic for 25 min followed by being reper- fused for 30 min. The coronary flow, the content of myocardial malondialdehyde （MDA） , the activity of myocardial superoxide dismutase （SOD） and the myocardial infraet size were observed. RESULTS 5 μmol · L^-1 Pilocarpine increased the coronary flow ＇after being reperfused for5 rninand 10 min,which reached up to （5.7±1.2） mL·min^-1（P〈0.01）and （5.4±1.2） mL·min（P〈0.05）, respectively;by contrast,the coronary flow of the ischemia-reperfusion group reached up to （4. 1 ± 1.0） mL · min^-1 and （4. 1±0.8） mL · min^-1. Compared with the myocardial ischemial ischemia-reperfusion group,the content of myocardial MDA was decreased from （14. 3 ± 4. 1 ） μmol · g^-1 to （ 10. 1 ± 2. 5 ） μmol · g^-1 （ P 〈 0. 05 ） and the activity of myocardial SOD was increased from （ 128 ± 36 ） U · mg^-1 to （183 ± 65） U · mg^-1（ P 〈 0. 05 ） after an administration of pilocarpine. Meanwhile,the myocardial infract size was decreased from （37.8 ± 13.6 ） % to （ 24. 9 ± 6. 3 ） % （ P 〈 0. 05 ） after an administration of pilocarpine. However, the protective effects of pilocarpine on myocardial ischemia-reperfusion injury were inhibited by 3 nmol· L^-1 4-diphenylacetoxy-N-methylpiperidine-methiodide （4-DAMP） ,a selective M3 receptor antagonist. CONCLUSION M3 receptor agonist pilocarpine has a protective role in myocardial is-chemia-reperfusion injury of insolated rat hearts via stimulating myocardial M3 receptors.

关 键 词：M3 受体 毛果芸香碱 4-dipl:enylacetoxy-N-methylpiperidine-methiodide(4-DAMP) 心肌缺血再灌注损伤 

分 类 号：R965[医药卫生—药理学]