金丝桃苷调控miR-375/CXCL1轴影响脑缺血再灌注损伤研究  

Effects of Hyperoside on cerebral ischemia-reperfusion injury by regulating miR-375/CXCL1 axis

作　　者：夏丽秀 肖瑞 郑莉 XIA Lixiu;XIAO Rui;ZHENG Li(Department of Geriatrics,Hubei Integrated Traditional Chinese and Western Medicine Hospital,Wuhan,Hubei 430000,China)

机构地区：[1]湖北省中西医结合医院老年病科,武汉430000

出　　处：《重庆医学》2023年第4期583-589,共7页Chongqing medicine

基　　金：湖北省自然科学基金项目(2019CFB398)。

摘　　要：目的研究金丝桃苷(Hyp)调控miR-375/C-X-C趋化因子配体1(CXCL1)轴对脑缺血再灌注损伤(I/R)的作用机制。方法采用生物信息学分析影响I/R的潜在基因及miRNA,最终将CXCL1/miR-375纳入研究。收集I/R患者血浆用于检测miR-375/CXCL1的表达,对细胞进行氧葡萄糖剥夺/复氧(OGD/R)处理,建立体外I/R模型,检测细胞内miR-375/CXCL1的表达。采用CCK-8试剂盒分析细胞活力,流式细胞术分析细胞凋亡程度,双荧光素酶报告试验分析miR-375/CXCL1的调控关系。结果CXCL1在I/R患者血浆与OGD/R细胞模型中的表达异常升高(P<0.05)。Hyp能抑制CXCL1在OGD/R细胞模型中的表达。Hyp能提高OGD/R细胞活力,抑制OGD/R诱导的细胞凋亡(P<0.05);过表达CXCL1能降低细胞增殖活力、增加凋亡(P<0.05)。CXCL1被证明是miR-375的下游靶点,miR-375在I/R患者血浆与OGD/R细胞模型中均表达降低(P<0.05)。抑制miR-375能部分逆转Hyp作用,敲减CXCL1也能部分逆转miR-375抑制剂的作用。结论Hyp通过上调miR-375抑制CXCL1对脑I/R损伤起到保护作用。Objective To study the mechanism of Hyperoside(Hyp)on cerebral ischemia-reperfusion(I/R)injury by regulating microRNA-375(miR-375)/C-X-C ligand 1(CXCL1)axis.Methods Potential genes and miRNA affecting I/R were analyzed by bioinformatics,and CXCL1/miR-375 was finally included in the study.Plasma was collected from I/R patients to detected miR-375/CXCL1 expression,and the cells were treated with oxygen glucose deprivation/reoxygenation(OGD/R)to establish I/R modelin vitro,then the expression of miR-375/CXCL1 in cells was detected.Cell Counting Kit-8(CCK-8)was used to analyze cell viability,flow cytometry was used to analyze the degree of cell apoptosis,and the regulatory relationship of miR-375/CXCL1 was analyzed by dual lucifase reporter assay.Results CXCL1 expression was abnormally increased in plasma of I/R patients and OGD/R cell model(P<0.05).CXCL1 expression was inhibited by hyperoside in OGD/R cell model.Hyperoside increased the viability of OGD/R cells,inhibited cell apoptosis induced by OGD/R(P<0.05).Overexpression of CXCL1 decreased cell viability,increased apoptosis.CXCL1 was proved to be the downstream target of miR-375.The expression of miR-375 decreased in plasma of I/R patients and OGD/R cell model(P<0.05).The effects of Hyp was partially reversed by inhibition of miR-375,and the effects of miR-375 inhibitor was partially reversed by knockdown of CXCL1.Conclusion Hyp protects brain I/R by up-regulating miR-375 and inhibiting CXCL1.

关 键 词：金丝桃苷 miR-375 CXCL1 脑缺血再灌注损伤 氧葡萄糖剥夺/复氧 

分 类 号：R743[医药卫生—神经病学与精神病学]