基于miR-153/TREM1探讨健神利水方对脑出血大鼠神经细胞凋亡的作用机制  

Mechanism of Jianshen Lishui Decoction on Nerve Cell Apoptosis in Rats with Cerebral Hemorrhage Based on miR-153/TREM1

作　　者：高玉广[1] 钟洁[1] 刘永辉[1] 黄德庆[1] 黄树武[1] 刘泰[1] GAO Yuguang;ZHONG Jie;LIU Yonghui;HUANG Deqing;HUANG Shuwu;LIU Tai(The First Affiliated Hospital of Guangxi University of Traditional Chinese Medicine,Nanning 530023,China)

机构地区：[1]广西中医药大学第一附属医院,南宁530023

出　　处：《世界科学技术-中医药现代化》2024年第3期829-836,共8页Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology

基　　金：广西壮族自治区教育厅高校中青年教师科研基础能力提升项目(2020KY07015):健神利水颗粒对大鼠脑出血后脑组织水肿标志物AQP-4、MMP-9的影响,负责人:高玉广;广西壮族自治区中医药管理局自筹经费科研课题(GZZC2020036):健神利水方对急性脑出血患者C反应蛋白的影响研究,负责人:高玉广。

摘　　要：目的探究健神利水方对脑出血大鼠神经细胞凋亡的作用机制。方法通过miRNA微阵列芯片和RT-PCR分析出脑出血中miR-153的表达,观察并分析miR-153与脑出血神经细胞凋亡关系;预测miR-153的靶基因,采用双荧光素酶报告基因实验观察其与靶基因的结合情况,观察过表达和抑制miR-153对靶基因的影响,随后,明确靶基因与脑出血神经细胞凋亡关系,最后观察健神利水方对miR-153、靶基因的影响,最终探究健神利水方对脑出血大鼠神经细胞凋亡的相关机制。结果微阵列芯片和RT-PCR检测表明miR-153在脑出血中是低表达的(P<0.05),miR-153与神经细胞凋亡呈负相关(R:-0.875,P=0.0002)。在线数据库TargetScan和miRDB显示miR-153与TREM1具有结合区域,双荧光素酶报告基因实验证明两者具有结合关系,当miR-153过表达时,TREM1表达量会下调,相反,当miR-153抑制时,TREM1表达量会上调,TREM1与神经细胞凋亡呈正相关(R:0.857,P<0.001)。健神利水方组的TREM1表达量、神经细胞凋亡数量、神经功能缺损评分均低于模型组(P<0.05),miR-153表达量高于模型组(P<0.05)。健神利水方+miR-153抑制组的TREM1表达量、神经细胞凋亡数量、神经功能缺损评分均高于健神利水方组(P<0.05)。结论健神利水方通过促进miR-153表达,抑制TREM1表达来达到抑制脑出血大鼠神经细胞凋亡,保护神经功能。Objective To explore the mechanism of Jianshen Lishui Decoction on nerve cell apoptosis in rats with cerebral hemorrhage.Methods The expression of miR-153 in cerebral hemorrhage was analyzed by miRNA microarray and RTPCR,and the relationship between miR-153 and neuronal apoptosis in cerebral hemorrhage was observed,and predicted the target gene of miR-153;the binding of miR-153 to target genes was studied by dual-luciferase reporter gene Experiments,and to observe the effects of overexpression and inhibition of mi R-153 on target genes.Subsequently,the relationship between target genes and neuronal apoptosis in cerebral hemorrhage was determined.Finally,the effect of Jianshen Lishui Decoction on miR-153 and the target gene,and finally explored the related mechanism of Jianshen Lishui Decoction on nerve cell apoptosis in rats with cerebral hemorrhage.Results Microarray chip and RT-PCR detection showed that miR-153 was lowly expressed in cerebral hemorrhage(P<0.05),and miR-153 was negatively correlated with neuronal apoptosis(R:-0.875,P=0.0002).The online databases Target Scan and mi RDB showed that miR-153 has a binding region with TREM1,and the dual-luciferase reporter gene demonstrated a binding relationship between the two.When miR-153 was overexpressed,the expression of TREM1 was down-regulated,conversely,up-regulated when miR-153 was repressed,and TREM1 was positively correlated with nerve cell apoptosis(R:0.857,P<0.001).The expression of TREM1,the number of nerve cell apoptosis and the score of Neurological Deficit Scores in the Jianshen Lishui Decoction group were lower than those in the model group(P<0.05),and the expression of miR-153 was higher than that in the model group(P<0.05).The expression of TREM1,the number of nerve cell apoptosis and the score of Neurological Deficit Scores in the Jianshen Lishui Decoction+miR-153 inhibition group were higher than those in the Jianshen Lishui Decoction group(P<0.05).Conclusion Jianshen Lishui Decoction inhibits the apoptosis of nerve cells and protects the neuro

关 键 词：脑出血 健神利水方 miR-153 TREM1 外泌体 神经细胞凋亡 

分 类 号：R285.5[医药卫生—中药学]