雷诺定受体介导的BK通道开放在他克莫司对大鼠胸主动脉舒张中的作用  

Influences of ryanodine receptor mediated BK channel activation in vasodilation of rat thoracic aorta by tacrolimus

作　　者：汪洵[1] 张蕊[1] 陈玉芳[1] 马嵘[1] 向继洲[1] 汤强[1] 

机构地区：[1]华中科技大学同济医学院基础医学院药理学系,湖北武汉430030

出　　处：《中国医院药学杂志》2015年第13期1196-1199,共4页Chinese Journal of Hospital Pharmacy

基　　金：华中科技大学自主创新基金(2013年);国家自然科学研究基金(青年基金项目)(编号:81102439)

摘　　要：目的:探究他克莫司对大鼠胸主动脉的舒张作用及其机制。方法:采用多道生理记录仪测定大鼠胸主动脉环张力,观察他克莫司对去甲肾上腺素诱导收缩的胸主动脉血管环的舒张作用,并观察伊比蝎毒素(选择性大电导钙离子激活的钾离子通道抑制剂)和雷诺定(Ryanodine,肌浆网钙离子释放抑制剂)对他克莫司舒张曲线的影响。结果:他克莫司对去甲肾上腺素(NE1.0×10-6 mol·L-1)预收缩有内皮和去内皮大鼠胸主动脉环均有显著地舒张作用,且非内皮依赖性途径在他克莫司对血管的舒张作用中起着重要作用,他克莫司对NE预收缩的去内皮大鼠胸主动脉环的舒张作用,可被雷诺定(10μmol·L-1)和iberiotoxin(100 nmol·L-1)抑制,分别从(17.41±1.94)%降至(12.38±1.17)%(雷诺定孵育前后比较,P<0.05,n=7)和(16.69±2.66)%降至(10.46±1.17)%(iberiotoxin孵育前后比较,P<0.05,n=7)。结论:他克莫司对血管的舒张作用主要是通过雷诺定受体引起钙火花的释放,从而激活大电导钙离子激活的钾离子通道(BK通道)开放引起的。OBJECTIVE To investigate vasodilative effects and mechanism of tacrolimus on rat thoracic aorta.METHODS Tensionof rat thoracic aorta ring was measured by using multi-channel physiological recording instrument.Effects of tacrolimus on norepinephrine induced contraction on thoracic aorta rings were observed,and effects of iberiotoxin（selective inhibitor of large conductance calcium activated potassium channel）and Ryanodine（potent inhibitor of Ca2＋release from sarcoplasmic reticulum）on vasodilative curves of tacrolimus were also investigated.RESULTS Tacrolimus caused significant vasodilative effects on norepinephrine（NE,1×10-6 mol·L-1）induced contraction in rat thoracic aorta rings with or without endothelium,and endothelium independent pathway played a major role in vasodilative effects of tacrolimus.Endothelium independent vasodilative effects were inhibited by Ryanodine（10μmol·L-1）and iberiotoxin（100 nmol·L-1）from（17.41±1.94）%to（12.38±1.17）%（control vs.Ryanodine,P〈0.05,n=7）and（16.69±2.66）%to（10.46±1.17）%（control vs.iberiotoxin,P〈0.05,n=7）.CONCLUSION BK channel activation caused by calcium sparks released through Ryanodine receptor plays a critical role in vasodilative effects of tacrolimus on rat thoracic aorta.

关 键 词：他克莫司 胸主动脉 血管舒张 雷诺定受体 大电导钙离子激活的钾离子通道 

分 类 号：R979.5[医药卫生—药品]