LncRNA KCNQ1OT1调控miR-324-5p对糖尿病心肌病大鼠心肌损伤的影响

doi:10.3969/j.issn.1006-6233.2025.09.04

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摘要 目的: 探究长链非编RNA(LncRNA)KCNQ1重叠转录物1(KCNQ1OT1)调控微小RNA-324-5p(miR-324-5p)对糖尿病心肌病(DCM)大鼠心肌损伤的影响。方法: 利用高糖高脂饲料喂养联合腹腔注射链脲佐菌素(STZ)建立DCM大鼠模型,后随机将大鼠分为DCM组、sh-NC组、sh-KCNQ1OT1组、sh-KCNQ1OT1+antiagomir-NC组、sh-KCNQ1OT1+miR-324-5p antiagomir组,每组12只,再取12只健康大鼠为对照组,并以普通饲料喂养。血糖仪检测各组大鼠空腹血糖(FBG)水平;超声心动图检测各组大鼠心功能参数;ELISA检测各组大鼠血清中BNP、cTnⅠ水平;HE染色观察各组大鼠心肌组织病理变化;TUNEL染色检测各组大鼠心肌组织细胞凋亡状况;qRT-PCR法检测各组大鼠心肌组织中LncRNA KCNQ1OT1、miR-324-5p表达水平;双荧光素酶报告基因实验检测LncRNA KCNQ1OT1与miR-324-5p的靶向关系。结果: DCM组大鼠LVFS、LVEF、LVSP以及miR-324-5p表达显著低于对照组,LVSD、FBG、BNP和cTnⅠ水平、细胞凋亡率以及LncRNA KCNQ1OT1表达显著高于对照组(P<0.05);sh-KCNQ1OT1组大鼠的LVFS、LVEF、LVSP以及miR-324-5p表达显著高于DCM组和sh-NC组,LVSD、FBG、BNP和cTnⅠ水平、细胞凋亡率以及LncRNA KCNQ1OT1表达显著低于DCM组和sh-NC组(P<0.05);sh-KCNQ1OT1+miR-324-5p antiagomir组大鼠LVFS、LVEF、LVSP以及miR-324-5p表达显著低于sh-KCNQ1OT1组和sh-KCNQ1OT1+antiagomir-NC,LVSD、FBG、BNP和cTnⅠ水平、细胞凋亡率显著高于sh-KCNQ1OT1组和sh-KCNQ1OT1+antiagomir-NC(P<0.05);且双荧光素酶报告基因实验证实LncRNA KCNQ1OT1可以靶向抑制miR-324-5p表达(P<0.05)。结论: 干扰LncRNA KCNQ1OT1可靶向上调miR-324-5p以改善DCM大鼠的心肌损伤。

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关键词 ：长链非编RNA KCNQ1重叠转录物1, 微小RNA-324-5p, 糖尿病心肌病大鼠, 心肌损伤

Abstract：Objective: To explore the effect of long non-coding RNA (LncRNA) KCNQ1 overlapping transcript 1 (KCNQ1OT1) on myocardial damage in diabetic cardiomyopathy (DCM) rats by adjusting microRNA-324-5p (miR-324-5p). Methods: A DCM rat model was established by feeding high glucose and high-fat diet combined with intraperitoneal injection of streptozotocin (STZ). The rats were stochastically divided into DCM group, sh-NC group, sh-KCNQ1OT1 group, sh-KCNQ1OT1+antiagomir-NC group, and sh-KCNQ1OT1+miR-324-5p antiagomir group, each had 12 rats. Another 12 healthy rats were designated as control group and fed with regular food. The blood glucose meter was used to detect the fasting blood glucose (FBG) in each group. Echocardiography was used to detect cardiac function parameters in each group. ELISA was performed to detect the BNP and cTnⅠ in serum. HE staining was performed to observe the pathological changes of myocardial tissue. TUNEL staining was used to detect the apoptosis status of myocardial tissue cells. QRT-PCR was performed to detect the LncRNA KCNQ1OT1 and miR-324-5p in the myocardial tissues. In addition, dual luciferase reporter gene assay was used to detect the targeting relationship between LncRNA KCNQ1OT1 and miR-324-5p. Results: The DCM group had conspicuously lower LVFS, LVEF, LVSP, and miR-324-5p, and conspicuously higher LVSD, FBG, BNP, cTnⅠ, cell apoptosis rate, and LncRNA KCNQ1OT1 than control group (P<0.05). The sh-KCNQ1OT1 group had conspicuously higher LVFS, LVEF, LVSP, and miR-324-5p, and conspicuously lower LVSD, FBG, BNP, cTnⅠ, cell apoptosis rate, and LncRNA KCNQ1OT1 than the DCM and sh-NC groups (P<0.05). The sh-KCNQ1OT1+miR-324-5p antiagomir group had conspicuously lower LVFS, LVEF, LVSP, and miR-324-5p, and conspicuously higher LVSD, FBG, BNP, cTnⅠ, cell apoptosis rate, and LncRNA KCNQ1OT1 than the sh-KCNQ1OT1 group and sh-KCNQ1OT1+antiagomir-NC (P<0.05). And the dual luciferase reporter gene experiment confirmed that LncRNA KCNQ1OT1 could target the inhibition of miR-324-5p (P<0.05). Conclusion: Interference with LncRNA KCNQ1OT1 can target upregulation of miR-324-5p to improve myocardial damage in DCM rats.

Key words： Long non-coding RNA KCNQ1 overlapping transcript 1 MicroRNA-324-5p Diabetic cardiomyopathy rats Myocardial damage

基金资助:河北省卫生健康委政府资助临床医学优秀人才项目,(编号:ZF2023128);河北省省级科技计划项目,(编号:236Z7738G)

通讯作者: 郭炳彦

引用本文:

黄柳, 魏慧卿, 阎婕, 崔坤, 邱翔, 郭炳彦. LncRNA KCNQ1OT1调控miR-324-5p对糖尿病心肌病大鼠心肌损伤的影响[J]. 河北医学, 2025, 31(9): 1428-1434.
HUANG Liu, WEI Huiqing, YAN Jie, et al. Effects of LncRNA KCNQ1OT1 on Myocardial Injury in Diabetic Cardiomyopathy Rats by Adjusting miR-324-5p. HeBei Med, 2025, 31(9): 1428-1434.

链接本文:

http://www.hbyxzzs.cn/CN/10.3969/j.issn.1006-6233.2025.09.04 或 http://www.hbyxzzs.cn/CN/Y2025/V31/I9/1428

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