盐酸芬戈莫德抑制颈动脉球囊损伤后的血管炎症反应

背景：炎症因子在球囊损伤后血管狭窄的过程中起到关键作用，1型1-磷酸鞘氨醇受体可以增强炎症因子的表达，促进这一病理过程的发生发展。目的：观察大鼠颈动脉球囊损伤后炎症因子及1型1-磷酸鞘氨醇受体的表达变化和盐酸芬戈莫德减轻炎症反应的作用。方法：60只SD大鼠随机分为4组。空白对照组和阴性对照组仅分离左侧颈总动脉，结扎左侧颈外动脉；损伤组和药物干预组行左侧颈总动脉球囊损伤建立大鼠颈动脉损伤模型。阴性对照组与药物干预组以盐酸芬戈莫德1 mg/kg腹腔注射，空白对照组与损伤组用等量生理盐水腹腔注射，于第3，7和21天取材。结果与结论：苏木精-伊红染色显示损伤组血管增生明显，药物干预组血管增生厚度明显减轻，空白对照组与阴性对照组血管形态基本正常。实时荧光定量PCR显示药物干预组第7天环氧合酶2、前列腺素E2 mRNA的表达水平显著低于损伤组（P＜0.05），损伤组和药物干预组环氧合酶2、前列腺素E2 mRNA在同一时间点的表达水平明显高于空白对照组与阴性对照组（P＜0.05）；Western Blot显示的结果1型1-磷酸鞘氨醇受体的表达在损伤初期有较高的表达，损伤后期减少，特别是经过药物干预后蛋白表达进一步减少。结果提示盐酸芬戈莫德通过1型1-磷酸鞘氨醇受体调节环氧合酶-2、前列腺素E2mRNA的表达，抑制损伤血管的炎症反应，减轻损伤血管的狭窄。

Fingolimod hydrochlor!de suppresses inflammatory reaction of blood vessels after balloon injury of the carotid artery

BACKGROUND：Inflammatory factor plays an important role in restenosis after bal oon injury. Sphingosine1-phosphate receptor 1 can enhance the expression of inflammatory factor and promote development and progression of this pathological process.OBJECTIVE：To observe the expression of the inflammatory factors and sphingosine1-phosphate receptor 1 after bal oon injury of the rat carotid artery and effects of fingolimod hydrochloride on reducing inflammatory reaction.METHODS：Sixty Sprague-Dawley rats were equal y and randomly divided into four groups. In the blank control group and negative control group, left common carotid artery was only isolated, and left external carotid artery was ligated. In the bal oon injury group and drug intervention group, rat models of carotid artery injury wereestablished by bal oon injury on the left common carotid artery. In the negative control and drug intervention groups, the rats were intraperitoneal y injected with fingolimod hydrochloride 1 mg/kg. In the blank control and bal oon injury groups, the rats were intraperitoneal y injected with an equal volume of saline. Samples were col ected at 3, 7 and 21 days.RESULTS AND CONCLUSION： Hematoxylin-eosin staining showed that the proliferation of blood vessel was remarkable in the bal oon injury group, but attenuated in the drug intervention group. The appearance of blood vessels was normal in the blank control group and negative control group. Real-time fluorescent quantitative PCR revealed that cyclooxygenase 2 and prostaglandin E2 mRNA expression levels were significantly lower in the drug intervention group than those in the bal oon injury group at 7 days （P＆lt;0.05）. Cyclooxygenase 2 and prostaglandin E2 mRNA expression levels were significantly higher in the bal oon injury group and drug intervention group than those in the blank control group and negative control group at the same time point （P＆lt;0.05）. Western blot assay results revealed that sphingosine1-phosphate receptor 1 expression was high in early stage of injury, and then reduced in late stage of injury. In particular, protein expression further decreased after drug intervention. Results indicated that fingolimod hydrochloride suppressed inflammatory reaction of injured blood vessels and lessened the stenosis of injured blood vessels by regulating cyclooxygenase 2 and prostaglandin E2 mRNA expression using sphingosine1-phosphate receptor 1.