首页|CCL5调控IL-6/STAT5信号通路促进大鼠颅内动脉瘤进展的研究

CCL5调控IL-6/STAT5信号通路促进大鼠颅内动脉瘤进展的研究

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目的 探明趋化因子配体5(CCL5)激活IL-6/STAT5信号通路增加了颅内动脉瘤进展的分子机制.方法 构建颅内动脉瘤大鼠模型,分为NC组(空 白对照组)和颅内动脉瘤组(IA组),检测各组大鼠的颅内动脉瘤形成情况.TUNEL和免疫荧光实验检测神经元细胞凋亡情况和SM22-a的表达.HE和弹性纤维染色检测各组中血管内皮和弹性纤维变化.生物信息学筛选差异基因.随后构建IA+Cyclic MKEY TFA组(CCL5抑制剂),即IA+TFA组.ELISA和 WB检测IL-6、TNF-α、IL-1β、IL-8和STAT5的表达.结果 ELISA实验显示,相较于NC组,IA组的IL-6、TNF-α、IL-1β、IL-8和STAT5表达升高.生物信息学结果显示CCL5在1A组中表达升高.HE染色和弹性纤维染色结果显示,相较于NC组,IA组中动脉瘤形成明显,血管内壁增厚和弹性纤维减少,相较于IA组,IA+TFA组的血管内壁变薄且弹性纤维增多.TUNEL结果显示,相较于NC组,IA组中的TUNEL阳性细胞率升高,而相较于IA组,IA+TFA组的TUNEL阳性细胞率降低.WB结果显示,相较于IA组,IA+TFA组的IL-6、STAT5和CCL5表达降低.结论 CCL5调控IL-6/STAT5信号通路促进了颅内动脉瘤进展.
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.

chemokine ligand 5IL-6/STAT5 signaling pathwayintracranial aneurysmchemokine lig-and 5 inhibitors

闵敬亮、郭亚玲、张辉、王大巍

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蚌埠医科大学第二附属医院神经外科,安徽 蚌埠 233040

蚌埠医科大学第一附属医院肾脏内科,安徽 蚌埠 233004

趋化因子配体5 IL-6/STAT5信号通路 颅内动脉瘤 趋化因子配体5抑制剂

2024

右江民族医学院学报
右江民族医学院

右江民族医学院学报

影响因子:0.708
ISSN:1001-5817
年,卷(期):2024.46(6)