据统计,67％女性和33％男性心绞痛患者以及10％急性心肌梗死患者行冠状动脉造影(CAG)时并未见心外膜冠状动脉管腔有明显狭窄.在排除冠状动脉痉挛、血栓自溶、精神等因素后,CAG未见明显狭窄但患者仍有心肌缺血的症状,提示存在冠状动脉微循环障碍(CMD).CMD机制尚不明确,目前普遍认为导致CMD的机制主要有冠状动脉微循环栓塞(CME)、内皮功能障碍(ED)、心肌缺血再灌注损伤(MIRI)以及自主神经功能障碍(AD).非编码RNA(ncRNA)数量庞大且种类众多,大量研究发现其可通过上述机制参与CMD的发生发展.文章将着重综述微小RNA(microRNA,miRNA)、长链非编码RNA(lncRNA)和环状RNA(circRNA)在CMD发病和治疗中调控作用的研究进展.

AIM:To investigate the role of long non-coding RNA-taurine upregulated gene 1（lncRNATUG1） in myocardial injury after myocardial infarction（MI） in mice.METHODS:Forty C57BL/6 mice were randomly divided into sham group,MI group,MI+empty vector（shNC） group,and MI+lncRNA-TUG1 silencing（shTUG1） group.A lncRNA-TUG1 silencing adenovirus was constructed,and the mouse myocardium was infected.Mouse MI model was established by ligation of the left anterior descending branch of the coronary artery one week later.One week after the model was established,the changes of cardiac function in mice were measured by a small-animal ultrasound apparatus.Subsequently,orbital blood and cardiac tissue were collected.The expression of lncRNA-TUG1 in the MI area was detected by RT-qPCR.The levels of cardiac injury markers were assessed by ELISA.The MI area was compared by TTC staining.The changes of myocardial endothelial nitric oxide synthase（eNOS） and brain-derived neurotrophic factor（BDNF） levels in the MI area were detected by Western blot.Inflammatory cytokines and mitochondrial biosynthesis-related proteins were detected by Western blot,ELISA and RT-qPCR to evaluate the levels of inflammation and mitochondrial biosynthesis.RESULTS:（1） lncRNA-TUG1 expression was increased in heart tissue in the infarcted area after MI（P＜0.01）,and adenovirus infection effectively reduced lncRNA-TUG1 expression（P＜0.01）.（2） Compared with MI+shNC group,silencing of lncRNA-TUG1 decreased myocardial injury marker levels,improved cardiac function,and significantly reduced the infarcted area（P＜0.05）.（3） Down-regulation of lncRNA-TUG1 significantly reversed the decreases in eNOS and BDNF levels caused by MI（P＜0.05）.（4） Silencing of lncRNA-TUG1 attenuated inflammatory response and improved mitochondrial biosynthesis after MI（P＜0.05）.CONCLUSION:Inhibition of lncRNA-TUG1 attenuates cardiac function injury in mice after MI by affecting eNOS/BDNF-mediated inflammatory response and mitochondrial biosynthesis.

目的:体外探讨长链非编码RNA(lncRNA)牛磺酸上调基因1(TUG1)靶向Zeste同源物增强子2(EZH2)对缺氧心肌细胞的影响.方法:缺氧诱导HL-1细胞建立细胞损伤模型,构建沉默质粒(siTUG1)和阴性对照(siNC)并分别转染至HL-1细胞内,随机分成常氧(normoxia)组、低氧(hypoxia)组、hypoxia+siNC组和hypoxia+si-TUG1组.采用RT-qPCR检测lncRNA-TUG1在各模型组中的表达.通过CCK-8分析细胞活力.ELISA检测心肌损伤标志物和炎症因子水平.RT-qPCR检测线粒体生物合成相关转录调节基因和炎症因子的表达.Western blot检测线粒体生物合成相关转录调节蛋白的表达.通过染色质沉淀(ChIP)检测lncRNA-TUG1、EZH2、内皮型一氧化氮合酶(eNOS)和脑源性神经营养因子(BDNF)间的互作关系.结果:与normoxia组相比,hypoxia组和hypoxia+siNC组细胞的活力、线粒体生物合成相关转录调节基因的表达均显著降低(P<0.05),而心肌损伤标志物和炎症因子水平均显著升高(P<0.05);沉默TUG1可部分逆转上述改变.ChIP结果表明沉默TUG1可能抑制EZH2对eNOS和BDNF启动子区的结合(P<0.05).结论:lncRNA-TUG1可能通过EZH2途径参与缺氧诱导的HL-1细胞炎症反应以及线粒体功能障碍.lncRNA-TUG1表达降低可进一步影响EZH2与eNOS和BDNF启动子区的结合,这可能是沉默TUG1缓解缺氧诱导的HL-1细胞炎症反应和线粒体功能障碍的潜在机制.

AIM: To study the changes of serum IL-6, ADPN, Apelin, hs-CRP and VEGF levels in patients with RVO, and to explore their association with the occurrence and development of RVO from a molecular perspective.METHODS:Totally 72 cases of RVO, including 35 cases of central retinal vein occlusion(CRVO)and 37 cases of branch retinal vein occlusion(BRVO). They were divided into groups 1 and 2. 32 senile cataract patients were collected as control group. The time of onset, visual acuity, history of cardio cerebral vascular disease and Macular edema thickness were recorded. Enzyme linked immunosorbent assay was used to detect the expression of IL-6, ADPN, Apelin, hs-CRP and VEGF in blood serum, which were closely related to inflammation and arteriosclerosis.RESULTS: The mean value of Apelin in group BRVO was 6.69(4.25, 10.52)ng/mL, and CRVO group was 7.12(3.78, 8.58)ng/mL, and the two groups were higher than those in control group 1.19(0.74, 1.49)ng/mL(P<0.05). The mean value of ADPN in group BRVO was 8.06(4.67, 10.81)μg/mL, while in group CRVO was 9.74(4.10, 11.67)μg/mL. The mean value of IL-6 in group BRVO was 35.89(17.63, 37.50)pg/mL, while in group CRVO was 37.16(11.52, 42.80))pg/mL. The mean value of hs-CRP in group BRVO was 161.10(54.51, 164.01)μg/mL. The mean value of VEGF in group BRVO was 158.25(82.24, 230.41)pg/mL, while in group CRVO was 174.14(76.04,243.98)pg/ml(P>0.05). There was no significant difference between the experimental group and the control group.CONCLUSION:By comparing the levels of serum IL-6, ADPN, Apelin, hs-CRP and VEGF in 72 RVO patients and 32 senile cataract patients, Apelin was found to be higher than that in the control group. Apelin may be one of the related risk factors for RVO. The expression of ADPN, IL-6, hs-CRP, VEGF, RVO in acute stage no specificity.