LncRNA-MALAT1/miR-125b-5p/PDCD4分子轴参与心力衰竭发生发展的机制研究  

Mechanism of LncRNA-MALAT1/miR-125b-5p/PDCD4 Molecular Axis Involvement in the Occurrence and Development of Heart Failure

作　　者：赖纪英 郭宗文 岳霖琳 沈恩芳 欧阳松茂[1] 朱宏泉[1] LAI Jiying;GUO Zongwen;YUE Linin;SHEN Enfang;OUYANG Songmao;ZHU Hongquan(Department of Critical Care Medicine,The First Affiliated Hospital of Gannan Medical University,Ganzhou 341000,China)

机构地区：[1]赣南医学院第一附属医院重症医学科,江西赣州341000

出　　处：《中国医药指南》2023年第28期70-73,共4页Guide of China Medicine

基　　金：2022年江西省教育厅科学技术研究项目(GJJ2201449);2023年江西省卫生健康委科技计划项目(202310838)。

摘　　要：目的 探讨LncRNA-MALAT1/miR-125b-5p/PDCD4分子轴参与心力衰竭发生发展的机制。方法 购置SD大鼠40只,随机取大鼠10只为对照组,剩余大鼠30只采用结扎大鼠左冠状动脉前降支造成心肌梗死后形成心肌梗死模型,于第14日取材组织并完成HE染色;观察组随机分为模型组、空载组和MALAT1沉默组,利用慢病毒转染干扰LncRNA-MALAT1序列(LV-shMALAT1)及其空载(LV-Control)观察治疗大鼠的干预效果。采用实时荧光PCR法和Western Blot检测LncRNA MALAT1、miR-125b-5p和PDCD4表达水平;采用酶联免疫吸附试验测定炎性因子肿瘤坏死因子-α(TNF-α)和白细胞介素-1β(IL-1β)。结果 观察组EF及左室短轴缩短率低于对照组(P<0.05);MALAT1沉默组EF及左室短轴缩短率高于模型组及空载组(P<0.05);HE染色结果显示,模型组和空载组心肌纤维断裂,细胞核紊乱、肥大、间隙增宽、染色加深;MALAT1沉默组心肌纤维断裂有所改善,细胞排列相对整齐;MALAT1沉默组LncRNA MALAT1 mRNA、miR-125b-5p及蛋白表达低于模型组与空载组(P<0.05);PDCD4mRNA及蛋白表达高于模型组与空载组(P<0.05);模型组与空载组炎性因子TNF-α和IL-1β水平差异无统计学意义(P>0.05);MALAT1沉默组炎性因子TNF-α和IL-1β水平低于模型组与空载组(P<0.05)。结论 心力衰竭大鼠中LncRNA-MALAT1表达显著下调,能竞争性结合miR-125b-5p,使其解除对PDCD4的抑制,促进PDCD4表达,从而抑制炎性反应。Objective To explore the mechanism of the involvement of the LncRNA MALAT1/miR-125b-5p/PDCD4 molecular axis in the occurrence and development of heart failure.Methods Forty SD rats were purchased,and 10 rats were randomly selected as the control group.The remaining 30 rats were ligated with the anterior descending branch of the left coronary artery to create a myocardial infarction model.On the 14th day,tissue samples were taken and HE staining was completed.The observation group was randomly divided into model group,no-load group and MALAT1 silence group.The intervention effect of Lentivirus transfection interference LncRNA-MALAT1 sequence(LV shMALAT1)and its no-load(LV Control)were observed.Real time fluorescence PCR and Western blot were used to detect the expression levels of LncRNA MALAT1,miR-125b-5p,and PDCD4.Determination of inflammatory factor tumor necrosis factor using enzyme-linked immunosorbent assay-α(TNF-α)and interleukin-1β(IL-1β).Results The EF and left ventricular short axis shortening rate in the observation group were lower than those in the control group(P<0.05).The EF and left ventricular short axis shortening rate in the MALAT1 silent group were higher than those in the model group and the empty group(P<0.05).The HE staining results showed that the myocardial fibers in the model group and the empty group were broken,with disordered and enlarged nuclei,widened gaps,and deepened staining;the myocardial fiber rupture was improved in the MALAT1 silencing group,and the cell arrangement was relatively neat;the expression of LncRNA,MALAT1 mRNA,miR-125b-5p,and protein in the MALAT1 silencing group was lower than that in the model group and the empty group(P<0.05).The expression of PDCD4 mRNA and protein was higher than that of the model group and the empty group(P<0.05).Model group and empty group inflammatory factor TNF-αAnd IL-1βThere was no statistical difference in level(P>0.05).MALAT1 silencing group inflammatory factor TNF-αand IL-1βlevel was lower than that of the model group and the

关 键 词：心力衰竭 慢病毒转染 大鼠 LncRNA-MALAT1 miR-125b-5p PDCD4分子轴 

分 类 号：R541.61[医药卫生—心血管疾病]