阿魏酸对离体大鼠冠状动脉的舒张作用及机制探讨  

Vasodilatory effect of Ferulic acid on in-vitro rat coronary artery

作　　者：房龙梅 侯晓敏[1] 杨蓉[1] 范芳文[1] 贺泽芳[1] 石萌[1] 张明升[1] 

机构地区：[1]山西医科大学药理学教研室,山西太原030001

出　　处：《中国药理学通报》2016年第4期554-558,共5页Chinese Pharmacological Bulletin

摘　　要：目的探讨阿魏酸(ferulic acid,FA)对离体大鼠冠状动脉的舒张作用及机制。方法采用微血管张力法,测定FA对静息及预收缩大鼠离体冠状动脉舒张作用;观察内皮对FA舒张作用的影响;探讨FA舒张作用与细胞外钙内流和内钙释放的关系;应用钙激活K^+通道(K_(Ca))阻断剂四乙胺(TEA)、ATP敏感K^+通道(K_(ATP))阻断剂格列苯脲(Gli)、内向整流K^+通道(KIR)阻断剂氯化钡(BaCl_2)、电压依赖性K^+通道(K_V)阻断剂4-氨基吡啶(4-AP)、NOS抑制剂L-硝基精氨酸甲酯(L-NAME)、环氧酶抑制剂吲哚美辛(Indo)等工具药,探究FA舒张大鼠离体冠状动脉的作用机制。结果 FA对大鼠离体冠状动脉静息张力无明显影响;浓度依赖性的舒张KCl(60 mmol·L^(-1))、U46619(1μmol·L^(-1))、PE(10μmol·L^(-1))预收缩的大鼠冠状动脉(P<0.05);内皮对FA舒张作用无明显影响(P>0.05);FA能够明显抑制外钙依赖性和内钙释放引起的血管收缩(P<0.05);4-AP(1mmol·L^(-1))能抑制FA的舒张作用,TEA、Gli、BaCl_2、LNAME、Indo无明显影响(P>0.05)。结论 FA对离体大鼠冠状动脉的舒张作用可能与血管平滑肌细胞上KV通道激活、细胞肌浆网内钙释放、外Ca^(2+)通道的阻滞有关,与K_(Ca)、K_(ATP)、K_(IR)通道无关,也不依赖于内皮功能。Aim To investigate the vasodilatory effect of Ferulic acid on in vitro rat coronary artery and its possible mechanism. Methods By using the microvessel tension recorder system, the vasodilatory effect of FA on resting and contractin-vitro rat coronary artery was determined; the influence of endothelial integrity to FA-induced vasorelaxation was observed; the relationship of FA on [Ca^(2+)] ex-influx-induced and[Ca^(2+)] in-efflux-induced contractions was discussed;the mechanism of vasodilatory effect of FA was explored by applying the inhibitors of K_(Ca)( TEA),KATP channel( Gli),KIRchannel( BaCl_2),K_V( 4-AP),NOS( L-NAME) and COX( Indo). Results FA had no effect on the resting tension of in vitro rat coronary artery. FA dilated the in-vitro rat coronary artery pretreated with KCl( 60 mmol · L^(-1)),U46619( 1 μmol· L^(-1)) and PE( 10μmol· L^(-1)) in a concentrationdependent fashion( P < 0. 05). FA inhibited the[Ca^(2+)] ex-influx-induced and [Ca^(2+)] in-efflux-induced contractions significantly( P < 0. 05). 4-AP( 1mmol· L^(-1)) restrained the diastolic function of FA,while TEA,Gli,BaCl_2、L-NAME,Indo had no obvious effect( P > 0. 05). Conclusion The diastolic function could be related to the activation of K_V channel on vascular smooth muscle cells,the free Ca^(2+) from Sarcoplasmic reticulum cells and blockade extracellular Calcium channel do not depend on K_(Ca),K_(ATP),K_(IR) channel,nor the endothelial function.

关 键 词：FA 离体冠状动脉 舒张作用 作用机制 血管环 钾通道 钙通道 

分 类 号：R-332[医药卫生] R322.121