【作者】 李晋； 赵永攀； 邓春玉； 邝素娟； 严华成； 石磊； 李健； 赵树进；

【Author】 LI Jin;ZHAO Yong-pan;DENG Chun-yu;KUANG Su-juan;YAN Hua-cheng;SHI Lei;LI Jian;ZHAO Shu-jin;Pharmacy Department,Genenral Hospital of Guangzhou Military Command of PLA;School of Bioscience and Bioengineering,South China University of Technology;Medical Research Unit,Guangdong General Hospital;Cardiovascular Institute,Guangdong Provincial Academy of Medicine;Centers for Disease Control and Prevention of Guangzhou Military Command of PLA;

【机构】 广州军区广州总医院药学部； 华南理工大学生物科学与工程学院； 广东省人民医院医学研究部； 广东省医学科学院心血管病研究所； 广州军区疾病预防控制中心；

【摘要】 为研究CYP4A抑制剂HET0016对小鼠离体主动脉血管张力的影响,对雄性C57BL/6J小鼠进行脱臼处死后,取主动脉并剪成3～4 mm长的血管环,固定于微血管测定仪的浴槽内,分别用高钾溶液(KCl 60 mmol/L)和去氧肾上腺素(Phe1μmol/L)进行血管功能性检测均能让离体主动脉环产生持续性收缩,然后采用累积给药法观察溶剂对照组、1μmol/L Phe处理组、60 mmol/L高钾处理组、eNOS抑制剂L-NAME (100μmol/L)和L-钙通道阻滞剂nifedipine(1μmol/L)单独或共同孵育后Phe (1μmol/L)处理组中不同浓度HET0016对小鼠离体主动脉环张力的影响,并探讨其可能的作用机制。结果发现,高浓度的HET0016可以舒张高钾和Phe预收缩的内皮完整的主动脉环;对于L-NAME单独孵育后Phe预收缩的内皮完整的主动脉环,只有高浓度的HET0016有显著舒张作用;而对于nifedipine单独孵育以及L-NAME和nifedipine共同孵育后Phe预收缩的动脉环,HET0016的舒张作用呈明显的浓度依赖性。这些结果显示,HET0016这种舒张作用是多通道的,呈部分的内皮依赖性,但也不是主要通过L-电压门控钙通道产生,只有在高浓度的情况下才开始影响L-电压门控钙通道。更多还原

【Abstract】 In order to study the effect of CYP4 A inhibitor HET0016 on the tension of isolated mouse aorta, male C57 BL/6 J mice were put to death by dislocation and cut into aorta vascular ring 3～4 mm long in the bath of the micro vessel measuring instrument, respectively with high potassium solution(KCl 60 mmol/L)and phenylephrine(Phe 1 μmol/L) for vascular function detection can make isolated aortic rings produce sustained contraction, then the cumulative medication was used to observe the solvent control group, 1 mol/L Phe treatment group, 60 mmol/L KCl treatment group, eNOS inhibitor L-NAME(100 mol/L) and L-calcium channel blocker nifedipine(1 mol/L) alone or both together after CO incubation with Phe(1 mol/L) with different concentrations of HET0016 group to the effects of tension aorta rings in mice, and to explore its possible mechanism. The results showed that aortic ring endothelial HET0016 with high concentration can relax high potassium and Phe precontracted endothelium intact aortic rings; for contractile endothelium intact aortic rings precontracted by Phe after L-NAME incubation alone, only the high concentration of HET0016 has significant effect on diastolic arterial rings; for intact aortic rings precontracted by Phe was incubated by nifedipine separately and both L-NAME and nifedipine, the relaxation effect of HET0016 was obviously concentration dependent. These results suggest that the HET0016 relaxation effect is multi-channel, is part of the endothelium dependent, but is not mainly through by L-voltage-gated calcium channels, only in the case of high concentration began to affect the L-voltage-gated calcium channels.更多还原