15-羟廿碳四烯酸对缺氧性大鼠颈内动脉环的收缩作用及机制

Contractile effect and mechanism of 15-HETE on hypoxic rat ICA rings

目的研究15-羟廿碳四烯酸(15-HETE)对正常及缺氧状态的离体大鼠颈内动脉环的作用,探讨15-HETE在缺血/缺氧性脑损伤的病理生理过程中的作用.方法 16只Wistar大鼠随机分为两组即对照组:其氧浓度(FiO2)为21%和缺氧组:置于FiO2为10%的缺氧箱中(n=8).9 d后将大鼠处死,游离颈内动脉(ICA)制备血管环,KH液中分别加入不同浓度15-HETE以及2 mmol·L-1 4-AP、10-2 mol·L-1 TEA、10-6 mol·L-1 GLYB后平衡15 min后,再加入15-HETE,观察不同浓度15-HETE、不同K+通道阻断剂对颈内动脉环收缩反应程度的变化.结果 15-HETE以浓度依赖方式(10-8 mol·L-1～10-6mol·L-1)使游离颈内动脉环张力增加,对缺氧组大鼠颈内动脉环张力作用更为明显,与正常对照组相比差异有显著性(15-HETE浓度为10-8 mol·L-1、10-7 mol·L-1时,P<0.05,10-6 mol·L-1时,P<0.01,n=8);2 mmol·L-1 4-AP使颈内动脉环血管张力增高(P<0.05，n=8),但预先应用 2 mmol·L-1 4-AP后浴液中加入10-6 mol·L-1 15-HETE,血管张力无进一步增加的趋势;10-2 mol·L-1 TEA、10-6 mol·L-1 GLYB,对血管环张力差异无显著性(P>0.05,n=8);但进一步应用15-HETE使血管环张力增加,变化幅度接近单纯应用15-HETE组.结论 15-HETE收缩ICA,缺氧情况下尤为明显;Kv通道在15-HETE所致的ICA收缩中起作用.

Aim To eicosatetraenoic acid evaluate the effect of 15-hydroxy （15-HETE） on the tension of isolated internal carotid artery（ICA） rings in normoxic or hypoxic rats in order to find out the pathophysiological effect of 15-HETE in ischemic/hypoxic brain tissues. Methods Sixteen healthy Wistar rats were randomly divided into two groups （n = 8） ： group A with normal oxygen supply （ FiO2 21% ） and group B with hypoxia （ FiO2 10% ）. 9 days later, the rats were killed and the ICA rings were prepared. 15-HETE in different concentration were added accordingly, and the after washing up,blockers of different kinds of K ＋ channels such as 2 mmol · L^-1 4-AP, 10^-2 mol · L ^-1 TEA and 10^6 mol · L^-1 GLYB were added to the KH solution separately, followed by the administration of 10^-6 mol · L^-1 15-HETE. The isometric tension was recorded using a four-channel force-displacement transducer. Resuits The ICA tension was significantly increased both in groups A and B by 15-HETE in concentrationdependent manner （ P 〈 0. 05, n = 8 ） , especially in group B （ compared to the control P 〈0. 05 ）. 2 mmol· L^-1 4-AP significantly increased the rings＇ tension （ P 〈 0. 05, n = 8） but no difference of ICA tension was observed between 2 mmol· L^-1 4-AP and 2 mmol · L^1 4-AP＋10^-6 mol·L^-1 15-HETE （P〉0. 05,n= 8）. Furthermore, 10^-2 mol · L^-1 TEA, 10^-6 mol · L^-1 GLYB had little effects on the tension of rings. Application of 10^-6 mol · L^-1 15-HETE after administration of TEA or GLYB induced nearly the same increase in ICA tone as it happened in the group administered with 10^-6mol · L^-1 15-HETE alone. Conclusion 15-HETE can induce brain vasoconstriction especially under the hypoxic condition. Voltage-dependent potassium channels play an important role in 15- HETE induced constriction.