Research on CCL5 regulating IL-6/STAT5 signaling pathway to promote the progression of intracranial aneurysms in rats
Objective To investigate the molecular mechanisms underlying the enhanced progression of in-tracranial aneurysms through the activation of the IL-6/STAT5 signaling pathway by chemokine ligand 5(CCL5).Methods A rat model of intracranial aneurysms was established and divided into a normal control(NC)group and an intracranial aneurysm(IA)group.The formation of IA was assessed in rats from each group.TUNEL and immunofluorescence assay were conducted to evaluate neuronal apoptosis and the expres-sion of SM22-α,respectively.HE and elastic fiber staining were used to examine changes in vascular endotheli-um and elastic fibers across the groups.Differential genes were screened by bioinformatics.Subsequently,an IA+Cyclic MKEY TFA group(CCL5 inhibitor),referred to as the IA+TFA group,was established.ELISA and WB were employed to detect the expression levels of 1L-6,TNF-α,IL-1β,1L-8,and STAT5.Results ELISA results showed that the expression levels of IL-6,TNF-α,IL-1β,IL-8,and STAT5 were elevated in the IA group compared to the NC group.Bioinformatics results indicated that the expression of CCL5 was elevated in the IA group.HE and elastic fiber staining demonstrated that,compared to the NC group,the IA group ex-hibited significant aneurysm formation,thickening of the vascular intima,and a decrease in elastic fibers.In contrast,the IA+TFA group showed thinning of the vascular intima and an increase in elastic fibers compared to the IA group.TUNEL assays showed an elevated percentage of TUNEL-positive cells in the IA group com-pared to the NC group,whereas this percentage was reduced in the IA+TFA group compared to the IA group.WB results indicated reduced expressions of IL-6,STAT5,and CCL5 in the IA+TFA group compared to the IA group.Conclusion CCL5 promotes the progression of IA by regulating the IL-6/STAT5 signaling path-way.