医学分子生物学杂志2025，Vol.22Issue(4)：346-353,8.DOI:10.3870/j.issn.1672-8009.2025.04.007
miR-181c通过靶向MICU1调控肺移植小鼠心肺功能康复
Effect of miR-181c on Cardiopulmonary Function Rehabilitation in Mice Undergoing Lung Transplantation by Targeting MICU1
摘要
Abstract
Objective To investigate how miR-181c influences cardiopulmonary recovery after lung transplantation in mice by targeting mitochondrial calcium uniporter 1(MICU1).Methods Fifty-four adult male C57BL/6 mice were randomly assigned to six groups(n=9 each):Normal group,Lung Transplantation group,Lung Transplantation+inhibitor-NC group,Lung Transplanta-tion+miR-181c-inhibitor group,Lung Transplantation+miR-181c-inhibitor+si-NC group,and Lung Transplantation+miR-181c-inhibitor+si-MICU1 group.The Normal group underwent anesthe-sia and thoracotomy only;the other groups received autologous left lung orthotopic transplantation,followed by weekly tail-vein injections(0.2 mL)of saline or 10 nmol/mL inhibitor/siRNA for 60 days.qRT-PCR and Western blotting were use to detect miR-181c and MICU1 mRNA and protein expression levels.Dual-luciferase gene reporter assay was performed to verify the targeting relation-ship between miR-181c and MICU1.Pulmonary pathology was assessed by hematoxylin-eosin(HE)staining.Pulmonary function was assessed using a small animal pulmonary function test system[0.15 s forced expiratory volume as a percentage of forced vital capacity(FEV0.15/FVC),peak expiratory flow(PEF),maximum ventilation volume(MVV),diffusing capacity of the lung for carbon monoxide(DLCO),and residual volume(RV)].Cardiac function was detected using small animal ultrasound imaging technology[left ventricular ejection fraction(LVEF),left ven-tricular fractional shortening(LVFS),left ventricular end-diastolic diameter(LVEDD),left ven-tricular end-systolic diameter(LVESD),left ventricular end-diastolic volume(LVEDV),and left ventricular end-systolic volume(LVESV)].Results The expression level of miR-181c was el-evated and that of MICU1 was reduced in the Lung transplantation group versus those in the Normal group(P＜0.05),with a significant negative correlation(r=-0.378,P=4.21 ×10-4).miR-181c mimic suppressed MICU1-3' UTR-WT luciferase activity(P＜0.05)but not 3'UTR-MUT.Inhibition of miR-181c expression restored MICU1 expression,and reduced lung lesions,and improved FEV0.15/FVC,PEF,MVV,DLCO,LVEF,LVFS,and decreased RV,LVESD,LV-EDV,LVESV(all P＜0.05).These gains were abolished by co-silencing MICU1 and miR-181c(P＜0.05).Conclusion miR-181c impairs cardiopulmonary recovery after lung transplantation by targeting MICU1.miR-181c inhibition enhances post-transplant function.关键词
微小RNA-181c/线粒体钙单向转运蛋白1/肺移植/心肺功能康复Key words
microRNA-181c/mitochondrial calcium uniporter 1/lung transplantation/car-diopulmonary function recovery分类
医药卫生引用本文复制引用
不艾吉尔·艾力,米尔古丽·艾麦特,李春丽,段平秀,李金贤..miR-181c通过靶向MICU1调控肺移植小鼠心肺功能康复[J].医学分子生物学杂志,2025,22(4):346-353,8.基金项目
新疆维吾尔自治区自然科学基金(No.2024D01C72) This work was supported by a grant from the Natural Science Foundation of Xinjiang Uygur Autonomous Region(No.2024D01C72) （No.2024D01C72）
