Fingolimod hydrochloride suppresses inflammatory reaction of blood vessels after balloon injury of the carotid artery / 中国组织工程研究

ABSTRACT

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 were established 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<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<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.