黄芪注射液对高脂血症模型大鼠冠状小动脉平滑肌的作用及机制

Effects of astragalus membranaceus injection on smooth muscle cells of small coronary arteries in experimental hyperlipidemic rats

目的探讨黄芪注射液对高脂血症大鼠冠状小动脉平滑肌的舒张作用及其机制。方法采用高脂饮食诱导高脂血症大鼠模型,应用视频显微测量装置测定冠状小动脉内径。在去除冠状小动脉内皮后,观察累积浓度黄芪(0.01、0.03、0.1、0.3、1.0、3.0 g.L-1)对苯肾上腺素(PE)、KCl和4-氨基吡啶(4-AP)收缩的冠状小动脉作用及其对经格列苯脲、普萘洛尔、无钙液和无钙液加肝素预处理后的冠状小动脉作用。结果高脂血症模型组大鼠血清总胆固醇(CHO)、三酰甘油(TG)和低密度脂蛋白(LDL)与对照组相比差异具有统计学意义(P<0.05)。累积浓度的黄芪(0.03、0.1、0.3、1.0、3.0 g.L-1)对PE(1μmol.L-1)和KCl(30 mmol.L-1)预收缩的大鼠冠状小动脉产生剂量依赖性舒张(P<0.05)。经无钙液预处理后,黄芪(3.0 g.L-1)对冠状小动脉的舒张作用未被阻断(P<0.05);但经无钙液加肝素预处理后,该作用被抑制(P>0.05)。累积浓度的黄芪对4-AP(3mmol.L-1)预收缩血管舒张作用与对照组比有明显的舒张作用,并呈浓度依赖性(P<0.05)。而经普萘洛尔(1μmol.L-1)和格列苯脲(1μmol.L-1)预处理后,3.0 g.L-1的黄芪对PE预收缩血管舒张作用与对照组比较差异无统计学意义(P>0.05)。结论黄芪对高脂血症大鼠冠状小动脉平滑肌具有舒张作用。其机制可能与阻断血管平滑肌细胞内质网上的三磷酸肌醇敏感的钙离子通道,抑制内钙的释放及细胞膜KV通道有关。

AIM To investigate the effect and mechanisms of astragalus membranaceus （AM） injection on the tension of small coronary arteries in experimental hyperlipidemic rats. METHODS Experimental rots were fed with lipid emulsion for 4 weeks to establish the hyperlipidemic model. Then all rats＇ small coronary arteries （RSCA） were measured by videomicroscopy. When the endothelium of RSCA was removed, the effect of accumulated AM （0.01,0.03,0.1, 0.3,1.0,3.0 g·L^-1） on arteries in preconstricted with phenylephrine （PE）, KCl and 4-AP was observed. And to explore the mechanism farther, the RSCA were incubated with Ca^2＋ free medium, Ca^2＋ free medium plus heparin, pmpranolol or glibenclamide respectively before precontraction with PE. RESULTS RSCA had been preconstricted with PE（1umol·L^-1 ） and KC1（30 mmol·L^-1） before the concentration of AM was cumulated to 0.03,0.1,0.3,1.0,3.0 g·L^-1 As compared with the control, AM caused concentration-dependent relaxation （P 〈 0.05）. The effect by preconstricted with PE was not inhibited by Ca^2＋ free medium （ P 〈 0.05）. However, the effect was attenuated by the incubation with Ca^2＋ free medium and heparin（ P 〉 0.05）. RSCA had been preconstricted with 4-AP（3 mmol·L^-1 ） before the concentration of AM was cumulated to 0.01,0.03,0.1,0.3,1.0,3.0 g·L^-1. As compared with the control （ P 〈 0.05）, AM caused concentration-dependent relaxation. The effect by preconstricted with PE was not inhibited by propranolol or glibenclamide alone （ P 〉 0.05）. CONCLUSION AM can increase the relaxation of smooth muscle cells on RSCA. The mechanism may include the inhibition of intracellular calcium ions release by the 1,4,5-triphosphate inositol-receptor-dependent pathway and the relationship of voltage-gated potassium channels in vascular smooth muscle cells.