miR-340-5p通过调控JAK1/STAT3通路对心肌梗死大鼠免疫功能及心功能的影响OA
Impacts of miR-340-5p on Immune Function and Cardiac Function in Myocardial Infarction Rats by Regulating JAK1/STAT3 Pathway
目的:探究 miR-340-5p 通过调控 JAK 激酶 1(JAK1)/信号转导子和转录激活子 3(STAT3)通路对心肌梗死(MI)大鼠免疫功能及心功能的影响.方法:通过结扎冠状动脉左前降支建立MI 大鼠模型,并分为假手术组、MI 组、MI+NC 组、MI+miR-340-5p mimics 组、MI+miR-340-5p mimics+JAK1 抑制剂 filgotinib(FILGO1)组.评估 MI 大鼠心功能,TTC 染色测定 MI 大鼠心肌梗死面积,HE 染色检测心肌病变程度,ELISA 法检测炎症因子 TNF-α、IL-1α、IL-6 表达水平,流式细胞仪测定淋巴细胞亚群占比,TUNEL 法进行细胞凋亡检测,qRT-PCR 检测心肌组织中 miR-340-5p、JAK1、STAT3 mRNA水平,Western blot 检测心肌组织中 JAK1/STAT3 通路相关蛋白表达,双荧光素酶报告基因检测验证 miR-340-5p 和 JAK1 之间的关系.结果:与假手术组相比,MI 组大鼠心肌细胞出现肥大,细胞体积明显增大,形态变得不规则,梗死面积、CD8+、IL-6、IL-1α、TNF-α 表达水平、心肌细胞凋亡率、JAK1、STAT3 mRNA、p-JAK1/JAK1、p-STAT3/STAT3 水平升高,LVEF、LVFS、CD4+、miR-340-5p 水平降低(P<0.05);与 MI 组及 MI+NC 组比较,MI+miR-340-5p mimics 组和 MI+miR-340-5p mimics+FILGO1 组大鼠心肌细胞排列整齐,纹理清晰,梗死面积、CD8+、IL-6、IL-1α、TNF-α 水平、心肌细胞凋亡率、JAK1、STAT3 mRNA、p-JAK1/JAK1、p-STAT3/STAT3 水平降低,LVEF、LVFS、CD4+、miR-340-5p 水平升高(P<0.05),且 MI+miR-340-5p mimics+FILGO1 组上述指标变化幅度高于 MI+miR-340-5p mimics 组(P<0.05);双荧光素酶实验发现 miR-340-5p 和 JAK1 存在靶向关系(P<0.05).结论:miR-340-5p 通过抑制 JAK1/STAT3 通路改善 MI 大鼠的免疫功能及心功能.
Objective:To investigate the impacts of miR-340-5p on immune and cardiac functions in myocardial infarction(MI)rats by regulating JAK kinase 1(JAK1)/signal transducer and activator of tran-scription 3(STAT3)pathway.Methods:A myocardial infarction(MI)rat model was established by ligating the left anterior descending coronary artery,and assigned into sham operation group,MI group,MI+NC group,MI+miR-340-5p mimics group,and MI+miR-340-5p mimics+JAK1 inhibitor filgotinib(FILGO1)group.The cardiac function of MI rats was evaluated.TTC staining was used to determine the myocardial infarction ar-ea in MI rats.HE staining was performed to detect the degree of myocardial lesions.ELISA method was per-formed to measure inflammatory factors TNF-α,IL-1α,and IL-6.Flow cytometry was performed to determine the proportion of lymphocyte subsets.TUNEL method was used to detect cell apoptosis.qRT-PCR was used to detect the mRNA levels of miR-340-5p,JAK1,and STAT3 in myocardial tissue.Western blot was used to de-tect the expression of JAK1/STAT3 pathway-related proteins in myocardial tissue.In addition,dual luciferase reporter gene assay was used to validate the relationship between miR-340-5p and JAK1.Results:For the sham surgery group,the myocardial cells of rats in MI group showed hypertrophy,great increase in cell volume,and irregular morphology,the infarct size,CD8+,IL-6,IL-1α,TNF-α expression levels,myocardial cell apop-tosis rate,JAK1,STAT3 mRNA,p-JAK1/JAK1,p-STAT3/STAT3 levels raised,while LVEF,LVFS,CD4+,miR-340-5p decreased(P<0.05).For the MI group and MI+NC group,the myocardial cells of rats in MI+miR-340-5p mimics group and the MI+miR-340-5p mimics+FILGO1 group were arranged neatly and had clear textures,the infarct size,CD8+,IL-6,IL-1α,TNF-α levels,myocardial cell apoptosis rate,JAK1,STAT3 mRNA,p-JAK1/JAK1,p-STAT3/STAT3 levels decreased,while LVEF,LVFS,CD4+,miR-340-5p raised(P<0.05),and the MI+miR-340-5p mimics+FILGO1 group had larger changes in above indicators than the MI+miR-340-5p mimics group(P<0.05).Dual luciferase assay revealed a targeted relationship between miR-340-5p and JAK1(P<0.05).Conclusion:MiR-340-5p improves the immune and cardiac functions of MI rats by regulating JAK1/STAT3 pathway.
靳丹丹;李珊;刘沙沙;罗宏玉;李洁;史炜林;王伟
华北医疗健康集团邢台总医院内三科,河北 邢台 054000华北医疗健康集团邢台总医院内三科,河北 邢台 054000河北省保定市第一中心医院,河北 保定 071000河北省邢台市中心医院心脏康复科,河北 邢台 054000河北省邯郸市第一医院老年医学二科,河北 邯郸 056000河北省保定市第一中心医院,河北 保定 071000河北省保定市第一中心医院,河北 保定 071000
心肌梗死miR-340-5pJAK激酶1/信号转导子和转录激活子3通路免疫功能心功能
Myocardial infarctionmiR-340-5pJAK kinase 1/signal transducer and activator of transcription 3 PathwayImmune functionCardiac function
《河北医学》 2026 (4)
572-579,8
河北省医学科学研究课题计划项目,(编号:20261384)
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