小电导钙激活型钾通道SK3在大鼠偏头痛模型中脑干的表达变化

Change in the expression of small conductance calcium-activated potassium channel SK3 in the brain stem in a rat model of migraine

目的初步探讨小电导钙激活型钾通道SK3与大鼠偏头痛的关系,为研究偏头痛的发病机制,寻找新治疗靶点提供实验依据。方法 40只成年雌性SD大鼠随机分为对照组8只,模型组16只,干预组16只,后两组再随机分为发作期组和间歇期组,每组8只。按Tassorelli Cristina法复制偏头痛大鼠模型。对照组用生理盐水造模。干预组每天灌服氟桂利嗪2 ml(0.5 mg/kg),对照组每天灌服生理盐水2 ml。发作期组于第5次造模后3 h、间歇期组于第5次造模后4 d断头处死取脑干组织。RT-PCR法及Western法分别检测各组脑干SK3 mRNA及其蛋白的表达。结果模型组、干预组脑干SK3 mRNA及其蛋白的表达水平均较对照组下降(P<0.05),且各发作期组均较相应间歇期组更低(P<0.05);而模型发作期组与干预发作期组、模型间歇期组与干预间歇期组比较SK3 mRNA及其蛋白的表达水平无明显差异(P>0.05)。结论脑干SK3表达的降低可能与偏头痛的发生发展有关;氟桂利嗪防治偏头痛可能不是通过影响脑干SK3的表达量实现的。

Objective To investigate the association between small conductance calcium-activated potassium channel SK3 and migraine in rats, and to provide an experimental basis for the research on the pathogenesis of migraine and discovery of new therapeutic targets. Methods A total of 40 adult female Sprague-Dawley rats were randomly divided into control group with 8 rats, model group with 16 rats, and intervention group with 16 rats, and the latter two groups were further divided into acute episode group and interictal period group, with 8 rats in each group. The Cristina Tassorelli method was used to establish a rat model of migraine. The control group was treated with normal saline to establish the model. The rats in the intervention group were given flunarizine 2 ml （0.5 mg/kg） by garage every day, and those in the control group were given normal saline 2 ml by gavage every day. The rats in the acute episode group were decapitated at 3 hours after the fifth time of modeling, and those in the interictal period group were decapitated at 4 days after the fifth time of modeling; the brain stem was collected. RT-PCR and Western blot were used to measure the mRNA and protein expression of SK3 in the brain stem. Results Compared with the control group, the model group and the intervention group had significant reduc- tions in the mRNA and protein expression of SK3 （ P 〈 0.05 ）, and the acute episode groups had significantly lower mRNA and protein expression of SK3 than the corresponding interictal period groups （P 〈 0.05 ）. There were no significant differences in the mRNA and protein expression of SK3 between the acute episode group in the model group and that in the intervention group, as well as between the interictal period group in the model group and that in the intervention group （ P 〉 0.05 ）. Conclusions Reduced expression of SK3 inthe brain stem may be associated with the development and progression of migraine. The mechanism of action of flunarizine in the pre- vention and treatment of migraine may not be realized through its effect on the expression of SK3 in the brain stem.