CYP4A抑制剂HET0016对小鼠离体主动脉血管张力的影响

The Effects of HET0016,the Inhibitor of CYP4A,on Tension of Isolated Aortic Rings of Mice

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（Phe 1μmol/L）进行血管功能性检测,发现二者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）预收缩处理组中不同浓度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预收缩的主动脉环,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。

In order to study the effect of CYP4 A inhibitor HET0016 on the tension of isolated mouse aorta,male C57BL/6J mice were put to death by dislocation and aortic vascular rings of 3-4 mm long were cut and fixed in the bath of the microvessel measuring instrument,respectively with high potassium solution（KCl60 mmol/L） and phenylephrine（Phe 1 μmol/L） for vascular function detection.It was found that both made isolated aortic rings produce sustained contraction.Then the cumulative medication was used to observe the effects of different concentrations of HET0016 on tension of aorta rings in 1 μmol/L Phe treatment group,60 mmol/L KCl treatment group,1 μmol/L Phe treatment group after incubation with e NOS inhibitor L-NAME（100 μmol/L） or L-calcium channel blocker nifedipine（1 μmol/L）,or the both,and to explore its possible mechanism.The results showed that HET0016 with high concentration could relax high potassium and Phe precontracted endothelium-intact aortic rings;for endothelium-intact aortic rings precontracted by Phe after L-NAME incubation alone,only the high concentration of HET0016 had significantly relaxing effect;for intact aortic rings precontracted by Phe and incubated with nifedipine alone or with both L-NAME and nifedipine,the relaxing effect of HET0016 was obviously concentration-dependent.These results suggest that the relaxing effect of HET0016 is of multi-channel,partly endothelium-dependent,but is not mainly through L-voltagegated calcium channels,and that only high concentration affects the L-voltage-gated calcium channels.