MiRNA-423-5p Suppresses The Formation Of Collateral Circulation Of Ischemic Hindlimb In Rats By Targeting S1PR1

Background: Collateral circulation is a naturally occurring way to improve blood supply to ischemic tissues,however,the mechanism of collateral circulation is still unclear.MiRNA can simultaneously regulate a variety of target genes,and several studies have shown that miRNA plays an important role in regulating the formation of collateral circulation.Objective: The purpose of this study was to investigate the effect of miRNA-423-5p on the formation of collateral circulation and its target genes through cell test and establishment of the rat model of hind limb ischemia.Methods: The subjects of this study were male SD rats.Thirty SD rats were divided into the sham operation group,the agomir-NC group and the agomir-423-5p group.The left femoral artery of the hind limb of rats was ligated to establish an animal model of hind limb ischemia,and blank buffer,agomir-NC and agomir-423-5p were injected into the adductor muscles of the ischemic hind limb of rats.Observed the hind limb movement of rats,laser speckle imaging technology was used to detect the blood flow of rat hind limb,the number,diameter and area of collateral vessels of rat hind limb adductor muscle were detected by HE staining,and the expression of S1PR1 was detected by immunohistochemistry.Human umbilical vein endothelial cells were transfected with a miRNA mimic 423-5p to detect the expression of S1PR1 by western blot(WB).Results:(1)MiRNA mimic 423-5p can significantly down-regulate the expression of S1PR1.Under the intervention of agomir-423-5p,the blood perfusion,collateral circulation and S1PR1 expression of the ischemic hind limb of rats were decreased.Conclusion: MiRNA-423-5p can inhibit the formation of collateral circulation in the ischemic hind limb of rats.This regulatory effect of miRNA may be caused by the targeting S1PR1.