【作者】 杜智敏； 杭鹏洲； 李湘晖； 郭薇；

【Author】 DU Zhi-min1,2,HANG Peng-zhou1,2,LI Xiang-hui1,2,GUO Wei1 (1. Institute of Clinical Pharmacology,the Second Affiliated Hospital of Harbin Medical University,Harbin 150086,China; 2. Key Laboratory of Drugs Research,College of Heilongjiang Province,Harbin 150086,China )

【机构】 哈尔滨医科大学附属第二医院临床药学药物研究所； 黑龙江省普通高校药物研究重点实验室；

【摘要】 目的研究黄连水煎剂对糖尿病大鼠去内皮冠状小动脉平滑肌张力的影响及作用机制。方法通过腹腔注射链脲佐菌素(STZ,35mg·Kg-1)及高脂饮食的方法建立2型糖尿病大鼠模型,应用离体小动脉灌流技术研究去除血管内皮后,累积浓度黄连水煎剂对正常大鼠和糖尿病大鼠冠状小动脉平滑肌基础张力的影响,以及对PE、KCl预收缩的微血管环的作用;分别应用4-AP、格列本脲、无钙液、无钙液加肝素预处理去内皮冠状小动脉环,观察黄连水煎剂对PE收缩的去内皮冠状小动脉环张力的影响。结果黄连水煎剂对去内皮冠状小动脉基础张力和PE预收缩的去内皮冠状小动脉产生剂量依赖性舒张作用;而对KCl预收缩的去内皮冠状小动脉无作用。经4-AP预处理后,黄连水煎剂对PE收缩的去内皮冠状小动脉的舒张作用未被阻断,但经格列本脲、无钙液、无钙液加肝素预处理后,该作用被显著抑制。结论黄连水煎剂可舒张糖尿病大鼠去内皮冠状小动脉,其舒张作用可能与阻断KATP通道和IP3敏感的Ca2+通道,抑制细胞内钙的释放和外钙内流有关。更多还原

【Abstract】 OBJECTIVE To investigate the effect of Coptis decoction on the tension of smooth muscle in endothelium-denuded small coronary artery rings of diabetic rats and the underlying mechanisms. METHODS The diabetic model was established by injection with Streptozocin(STZ, i.p. 35mg·kg-1 ) and feeding with high fat diet. Videomicroscopy technique was used to determine the effect of Coptis decoction on the vasomotion of endothelium-denuded small coronary arteries.The effect of Coptis decoction on endothelium-denuded small coronary artery rings in resting tension, or pre-constricted with phenylephrine (PE) and KCl. Meanwhile, the rings were preincubated with 4-AP, glibenclamide, Ca2+-free medium, Ca2+-free medium plus heparin before preconstricted with PE. RESULTS Coptis decoction could dilate the endothelium-denuded small coronary artery rings. Moreover, it caused concentration-dependent relaxation when artery rings were pre-constricted with PE. Whereras it has no effect when pretreated with KCl. The relaxation effect of Coptis decoction was inhibited by glibenclamide, Ca2+-free medium, Ca2+-free medium plus heparin.However it could not by 4-AP. CONCLUSION The results indicate that Coptis decoction can dilate the endothelium-denuded coronary arteries of diabetic rats. The mechanism may involved KATP and intracellular Ca2+ effluxed and extracellular Ca2+ influx by 1,4,5-triphosphateinositol (IP3) –dependent pathway in vascular smooth muscle cell.更多还原