The basic helix-loop-helix (bHLH) transcription factor family is a large family of transcription factors with a basic helix-loop-helix structure. Members of the bHLH family play an important role in the growth and development of organisms. Transcription factor heart and neural crest derivatives expressed 1(HAND1) is a member of the bHLH family and is essential for heart development. HAND1 gene mutations are linked to the occurrence of congenital heart disease, cardiomyopathy, cardiac conduction system, and other cardiovascular diseases. Loss of HAND1 gene expression results in ventricular septal defect, atrioventricular valve malformation, double outlet right ventricular and so on. Overexpression of the HAND1 gene causes a defect in left ventricular development and an increased susceptibility to arrhythmia. The author primarily summarizes the progress of transcription factor HAND1 research in congenital heart disease, cardiomyopathy, cardiac conduction system, and other cardiovascular diseases, in order to aid in the early detection and treatment of cardiovascular disease.

OBJECTIVES:To study the association of ventricular septal defect (VSD) with rare variations in the promoter region of HAND2 gene, as well as related molecular mechanisms.METHODS:Blood samples were collected from 349 children with VSD and 345 healthy controls. The target fragments were amplified by polymerase chain reaction and sequenced to identify the rare variation sites in the promoter region of the HAND2 gene. Dual-luciferase reporter assay was used to perform a functional analysis of the variation sites. Electrophoretic mobility shift assay (EMSA) was used to investigate related molecular mechanisms. TRANSFAC and JASPAR databases were used to predict transcription factors.RESULTS:Sequencing revealed that three variation sites (g.173530852A>G, g.173531173A>G, and g.173531213C>G) were only observed in the promoter region of the HAND2 gene in 10 children with VSD, among whom 4 children had only one variation site. The dual-luciferase reporter assay revealed that g.173531213C>G reduced the transcriptional activity of the HAND2 gene promoter. EMSA and transcription factor prediction revealed that g.173531213C>G created a binding site for transcription factor.CONCLUSIONS:The rare variation, g.173531213C>G, in the promoter region of the HAND2 gene participates in the development and progression of VSD possibly by affecting the binding of transcription factors.

目的 探索自噬-溶酶体标记基因LC3B和LAMP2调控序列变异与退行性心脏瓣膜病(DHVD)的关联性.方法 对212例DHVD患者组与390例健康对照组的自噬-溶酶体系统标记基因LC3B和LAMP2调控序列(启动子)进行统计分析.采集研究对象的外周静脉血白细胞,提取基因组DNA,应用聚合酶链反应(PCR)扩增基因LC3B和LAMP2的启动子序列,Sanger测序法直接检测序列变异.运用卡方检验对单核苷酸多态性(SNPs)进行分析,TRANSFAC数据库预测序列变异改变与启动子相结合的转录因子.结果 共发现29个序列变异,包含13个SNPs.其中,6个LC3B基因启动子序列变异仅发现于DHVD患者,1个LAMP2基因启动子序列变异只存在于DHVD女性患者,其他序列变异在健康对照组和患者组共有.对SNPs的基因型和等位基因进行卡方检验和logistic回归分析显示,rs35227715的等位基因G与DHVD相关联,是DHVD的独立危险因素,致病风险是1.36倍;rs42900基因型CC和等位基因C与DHVD存在关联,两者的致病风险均为0.56倍,具有保护性作用.利用TRANSFAC数据库预测仅在DHVD患者中发现的序列变异位点相结合的转录因子,结果表明序列变异可改变与之结合的转录因子.结论 自噬-溶酶体系统标记基因LC3B和LAMP2启动子序列变异可能影响与之结合的转录因子,改变其表达水平,引起自噬-溶酶体系统的功能失调,从而导致DHVD的发病.

Objective:To investigate the relationship between acute myocardial infarction (AMI) and single nucleotide polymorphism (SNP) of cathepsin B(CTSB) gene promoter region rs1293312T/C site and the associated risk factors.Methods:A case-control study was performed to collect 201 AMI patients (AMI group) hospitalized in the Department of Cardiology, Affiliated Hospital of Jining Medical University from January 2021 to December 2021, and 204 healthy controls (control group) in the physical examination center. Following DNA sequencing data were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RELP) technique combined with sequence alignment. Following the Hardy-Weinberg balance test, the χ2 test was used for correlation analysis. Logistic regression was utilized to examine the relationship between various risk variables, SNP loci and the incidence of AMI.Results:The SNP loci revealed three genotypes, including CC, CT and TT. Hardy-Weinberg equilibrium (χ2=0.57, 1.68, all P>0.05) and the genotype distribution were both supported by the data. There were no significant differences (χ2=0.15, 0.01, all P>0.05) between the CC, TC, TT genotypes of the AMI group [34(16.92%), 91(45.27%), 76(37.81%)] and the control group [37(18.14%), 89(43.63%), 78(38.23%)], as well as the C and T alleles of the AMI group [159(39.55%), 243(60.45%)] and control group [163(39.95%), 245(60.05%)]. Logistic regression analysis in five different genetic models suggested that the SNP loci was not associated with the onset of AMI (all P>0.05).Conclusion:The population genetics of the CTSB gene promoter region polymorphism is provided by the CTSB gene promoter rs1293312 T/C SNP, which is not related to the onset of AMI.

[目的]探讨组织蛋白酶D基因启动子序列单核苷酸多态性与急性心肌梗死的关系.[方法]采用病例-对照研究方法,对357例急性心肌梗死患者和347例对照人群的组织蛋白酶D基因启动子采用聚合酶链反应扩增目的基因片段并测序,结合目的基因测序后的序列及比对,GenBank上查找相对应的单核苷酸多态性位点后进行数据统计和分析.运用Hardy-Weinberg平衡检验后,应用x2检验和t检验进行相关分析.采用Logistic回归对多种危险因素以及2个单核苷酸多态性位点与急性心肌梗死易感性进行关联性分析.用Haploview4.2软件和SHEsis在线软件进行连锁不平衡及单倍型分析.TRANSFAC数据库用于预测可能受单核苷酸多态性影响的转录因子的结合位点.[结果]Logistic回归分析结果显示年龄增大、吸烟史、高血压病史、甘油三酯增高是急性心肌梗死的独立危险因素(P＜0.05),可明显增加急性心肌梗死的患病风险;高密度脂蛋白、胆固醇是急性心肌梗死的保护因素(P＜0.05),可明显降低急性心肌梗死的患病风险,此结果可能与心肌梗死组服用调脂类药物有关,需进一步扩大样本进行分析.在组织蛋白酶D基因启动子序列中的2个单核苷酸多态性位点与急性心肌梗死发病无关联性.进行连锁不平衡和单倍型分析提示,该2个单核苷酸多态性位点处于同一个连锁不平衡区域(D'=1.000,R2=0.978),单倍体型均未增加急性心肌梗死易感性(P＞0.05).[结论]组织蛋白酶D基因启动区两个单核苷酸多态性位点为完全连锁不平衡.该2个单核苷酸多态性位点及其单倍体型与急性心肌梗死发病无相关性,但提供了组织蛋白酶D基因启动区多态性的群体遗传学资料.

Background Rare diseases have been increasingly recognized as unmet medical and health needs worldwide; a growing demand for the development of orphan drugs emerges subsequently. Therefore, it is of great interest for both the Chinese regulatory agency and pharmaceutical companies to keep tract on the clinical development of orphan drugs in China. Objective and method This study aims to reveal the current situation and trend of the clinical development of orphan drugs in China, based on the data collected from the Chinese official platform, dating from January 1, 2013 to December 31, 2021. Results A total of 331 clinical trials for orphan drugs were extracted from the platform, covering 31 rare diseases and 124 drugs. Increases were seen in the annual number of clinical trials and drugs being tested, with a sharp increase after 2018. About the disease types of the 331 trials, Parkinson disease (young-onset, early-onset) (86, 26%), hemophilia (70, 21%), homozygote hypercholesterolemia (60, 18%) were the most common. Furthermore, it was also observed that the largest number of clinical trial units for rare disease in east China (90, 41%) and the smallest number located in northwest China (18, 6%) and northeast China (18, 6%). Conclusions The growth trends illustrate the progress in clinical trial and drug development of rare diseases from 2013 to 2021. However, promoting orphan drugs development still is an important issue in China; at the same time, further efforts should be made for meet the unmet needs of disease types and balance the uneven distribution of medical resources for clinical trial on rare diseases.

目的:探讨TBX20基因启动子区的单核苷酸多态性(SNP)与扩张型心肌病(DCM)的相关性.方法:采用病例-对照研究方法,收集136例DCM患者和210例健康对照.采用PCR和Sanger测序的方法获得TBX20基因启动子区的SNPs.通过细胞转染和电泳迁移率变动分析(EMSA)对TBX20基因启动子区的SNPs进行遗传功能分析.采用卡方检验和两独立样本t检验对数据进行统计学分析.使用SNPStats在线软件进行相关性分析.结果:校正混杂因素后,rs73099190在共显性遗传模型和超显性遗传模型中的TC基因型和显性遗传模型中的TC+CC基因型均与DCM显著相关(OR=1.96,95％CI:1.20～3.20,P=0.019;OR=1.98,95％CI:1.22～3.24,P=0.006;OR=1.86,95％CI:1.15～3.03,P=0.012).转染结果显示,TBX20基因启动子区的SNPs显著改变了TBX20基因启动子的转录活性(P<0.01).进一步EMSA实验表明,rs1191745927和rs73099190影响了TBX20基因启动子与转录因子的结合.结论:DCM患者TBX20基因启动子的变异可能影响转录因子的结合,进而改变了TBX20基因的转录活性,可能作为罕见的低频危险因素促进DCM的发生发展.

目的 探讨ATG16L1基因启动子序列单核苷酸多态性(SNP)与急性心肌梗死(AMI)的相关性.方法 采用病例-对照研究方法,对285例AMI患者和296例对照人群的ATG16L1基因启动子采用聚合酶链反应扩增片段并测序,结合DNA测序后的序列及比对SNP数据库后进行数据统计和分析.运用Hardy-Weinberg平衡检验后,应用x2检验和t检验进行相关分析.采用Logistic回归对多种危险因素以及3个SNP位点与AMI易感性进行关联性分析.用Haploview 4.2软件和SHEsis在线软件进行连锁不平衡及单倍型分析.TRANSFAC数据库用于预测可能受SNP影响的转录因子的结合位点.结果 多因素Logistic回归分析结果显示男性、吸烟史、高血压是AMI的独立危险因素(P＜0.05),而高密度脂蛋白胆固醇是AMI的保护因素(P＜0.05).在ATG16L1基因启动子序列中的3个SNP(rs1816753、rs12476635、rs2289477)中,rs1816753的TC基因型与AMI间存在关联,可明显增加AMI的患病风险(OR=2.519,95％ CI:1.130 ～5.615,P=0.024).通过Haploview 4.2软件分析显示3个SNP之间呈强连锁.结论 ATG16L1基因启动子SNP可能与AMI易感性相关,rs1816753的TC基因型可能是AMI的遗传危险因素.

BackgroundTenofovir disoproxil fumarate has been recommended for pre-exposure prophylaxis (PrEP) to prevent HIV infection. Several studies have shown short but potent intermittent PrEP could provide comparable protection to daily PrEP in men, suggesting such dosing strategy might be useful in Chinese as well. The objective of this study was to evaluate the impact of different dosing strategies on plasma concentrations of tenofovir.MethodsAn open label study in 40 Chinese healthy volunteers, randomized to receive the WHO-recommended dose of tenofovir (300mg) at four different dosing intervals: twice weekly for 4 weeks; once daily for 4 weeks with one missing dose in weeks 2–4; once daily for 4 weeks with two missing doses in weeks 2–4; and once every other day for 12 days. Plasma samples were collected at pre-dose, weekly trough and 24h post last dose and assayed using HPLC-UV.ResultsThe tenofovir trough concentrations were below the lower limit of quantification with the twice weekly regimen. The trough concentrations (24h dosing interval) at the steady state were 51.7±12.1ng/ml and 53.5±13.8ng/ml (mean±SD) in the once daily groups. Missing doses, once or twice weekly, had no significant impact on trough concentrations. Prolongation of dosing interval to 48h resulted with concentrations at 24h and 48h (trough) of ∼40 and 20ng/ml, respectively.ConclusionsIntermittent tenofovir regimens resulted with remarkably low plasma concentrations in Chinese participants. Missing doses did not affect trough concentrations significantly.

Previous studies have shown that cathepsins are proteolytic enzymes that mediate protein hydrolysis in endosomes or lysosomes. Recently, accumulating studies have revealed that cathepsins also exist in the nucleus, cytoplasm, plasma membrane, and extracellular matrixes to mediate extracellular matrix protein degradation, signal transduction, and organelle protein processing and transport. Cathepsin B (CTSB) is one of the most abundant cathepsins in lysosomes, usually exists in the form of inactivated proenzyme, and has dual roles of endopeptidase and dipeptidase, which plays an important role in protein catabolism. In recent years, human studies and animal experiments have demonstrated that CTSB involves in many physiological and pathophysiological processes, such as extracellular matrix protein degradation, antigen presentation, and inflammatory body activation. These processes have been directly or indirectly implicated in the pathogenesis of cardiovascular diseases, including atherosclerosis, myocardial infarction and abdominal aortic aneurysm. And now, a large number of studies have found that SARS-CoV-2 enters host target cells through CTSB mediated pathway and leads to cell damage.The purpose of this review is to summarize the biological function of CTSB and related recent progress in cardiovascular diseases.

心血管疾病和癌症是最常见的慢性疾病,经常共存和互相依赖[1].但目前我国心血管疾病的患病率和病死率处于上升趋势,且其病死率高于肿瘤和其他疾病,位居我国第一位,占居民疾病死亡构成比的40％以上[2].冠状动脉疾病是影响全球人群的主要心血管疾病之一[3].是冠状动脉壁富含胆固醇的斑块积聚所致,在炎症的作用下,冠状动脉斑块破裂或侵蚀,导致血栓形成和急性心肌梗死(acute myocardial infarction,AMI)的发生[4].AMI是冠状动脉疾病的危急重症,其死亡占心血管疾病总死亡的20％以上,欧洲的一项研究表明,AMI患者5年生存率仅为55％[5].AMI的遗传率为50％～60％[6].但迄今为止,AMI的遗传原因及其潜在的分子机制仍很不清楚,新兴数据表明,低频和罕见遗传变异对AMI的发生发展有较大影响[7].GATA结合蛋白5(GATA binding protein 5,GATA5)作为GATA家族的重要一员,在先天性心脏病、心房颤动、高血压等心血管疾病的发生发展中发挥着不可或缺的作用[8-10].GATA5与AMI的相关性尚未有相关报道.因此,我们就GATA5在AMI发生发展中的作用做一简要综述.

Objective: To investigate the correlation between single nucleotide polymorphisms (SNPs) of SIRT1 gene promoter sequence and senile degenerative heart valvular disease (SDHVD). Methods: A total of 236 SDHVD patients and 285 healthy controls who visited the Affiliated Hospital of Jining Medical University between February 2012 and October 2016 were enrolled. SNPs of SIRT1 gene promoter were detected by Sanger sequencing. Typing and correlation were analyzed by χ(2) test and Logistic regression analysis. Haplotype and linkage disequilibrium were analyzed by Haploview4.2 software and SHEsis online software. The effect of SNPs on the binding of transcription factors to SIRT1 gene promoter was analyzed by electrophoretic mobility shift assay(EMSA). The transcription factors affected by SNPs were predicted by Transfac online software. Results: The frequency distribution of GG genotype of rs3740051 in the SDHVD group was significantly higher than that in the control group (χ(2)=4.855, P=0.028). There was a correlation between GG genotype of the rs3740051 and SDHVD. After adjusting for age, the risk of SDHVD in the carrier of GG genotype was 3.079 times higher than that of AA genotype(OR=3.079, 95%CI: 1.156-8.201, P=0.024). The five SNPs (rs3740051, rs932658, rs35995735, rs3740053 and rs2394443) showed strong linkage disequilibrium(D'>0.8). The haplotype analysis of the five SNPs (haplotype frequency<0 was ignored in the analysis) showed that 11 haplotypes (P<0.05) were formed, and the frequency of *A**C, AA**C, *AG*C, AAG*C, AA*AC, *AGAC and AAGAC in SDHVD group were significantly higher than that in control group (P<0.05, OR>1, 95%CI does not contains 1). EMSA showed that the color of the binding bands incubated by wild type probe and nucleoprotein was darker than that incubated by DNA sequence variation probe and nucleoprotein. Conclusion: The GG genotype of rs3740051 is associated with SDHVD and may be a risk genotype for SDHVD. The haplotype AC (across rs932658 and rs2394443) may be a dangerous haplotype of SDHVD. rs3740051 may affect the occurrence and development of SDHVD by interfering with the binding of FOXC protein to SIRT1 gene promoter.

目的:通过病例-对照研究,探讨GATA结合蛋白5(GATA binding protein 5,GATA5)基因启动子序列单核苷酸多态性(single nucleotide polymorphism,SNP)与急性心肌梗死(acute myocardial infarction,AMI)的相关性.方法:通过x2检验、logistic回归、单倍型分析、细胞转染及电泳迁移率变动分析(electrophoretic mobility shift assay,EMSA)对SNPs进行遗传及功能分析.结果:校正混杂因素后,rs80197101位点GA和GA+AA基因型与AMI显著相关(OR=2.280,95％CI:1.027～5.061,P=0.043;OR=2.312,95％CI:1.045～5.116,P=0.039).rs77067995位点CT和CT+TT基因型也与AMI显著相关(OR=2.280,95％CI:1.027～5.061,P=0.043;OR=2.312,95％CI:1.045～5.116,P=0.039).rs80197101和rs77067995呈完美连锁不平衡,两者形成的单倍型AT在AMI组的频率显著高于对照组(x2=6.960,P=0.008).EMSA及转染结果表明,这些SNPs通过影响转录因子与GATA5基因启动子的结合,显著增加GATA5基因启动子在HEK-293细胞和H9c2细胞中的转录活性(P<0.001).结论:GATA5基因启动子序列中的rs80197101与rs77067995可显著增加AMI的易感性.rs80197101的等位基因A和rs77067995的等位基因T可能是AMI的危险等位基因,单倍型AT可能是AMI的危险单倍型.

CRISPR/Cas9基因编辑技术以其独特的优势已经在生物医学领域中被广泛应用.利用该技术在人类心血管疾病的相关研究如:心肌细胞水平、先天性心脏病动物模型建立、冠心病高危因素、心律失常、心力衰竭和心肌病等方面已经取得了很大进步,但目前的基因编辑技术在实际运用中仍然面临着许多问题.

白噬(autophagy)是真核细胞内的物质成分由溶酶体降解的过程,在真核细胞中普遍存在又相对保守.主要负责降解细胞质成分及受损细胞器、再循环,以提供细胞应对各种刺激环境,维持细胞内稳态[1].自噬有3种途径:巨细胞自噬(后文中的自噬均为巨细胞白噬)、微自噬和伴侣蛋白介导的自噬[2].自噬是细胞应激、饥饿下降解细胞质成分的重要途径,以维持细胞ATP生成和大分子物质形成间的平衡-靶.在自噬中,靶向细胞质成分被分离,包裹在“自噬小体”的双层膜囊泡,从细胞内脱离.自噬小体与溶酶体融合聚变,降解体内细胞成分,并将降解产物再循环利用[4].

Objective To analyze the clinical characteristic and identify the gene mutation in a family with hypertrophic cardiomyopathy,likely due to infantile Pompe disease.Methods Clinical data of two infants with hypertrophic cardiomyopathy in a family were collected.Peripheral leukocytes were collected from vein blood.Activity of acid α-glucosidase (GAA) in leukocytes were measured.The coding region of GAA gene was amplified by polymerase chain reaction,and then directly sequenced.Results Two infants from the same family were presented with mild macroglossia,dyspnea,generalized hypotoni,and hypertrophic cardiomyopathy at 4-5 months of age.The serum alanine aminotransferase,glutamic-oxaloacetic transaminase,creatine phosphokinase,creatine kinase-MB,lactate dehydrogenase,and hydroxybutyrate dehydrogenase was elevated.The GAA activities in leukocytes in the two infants were significantly lower than in normal controls.Gene sequencing revealed that two compound heterozygous mutations,c.1822C＞T and c.2297A＞C,in the two infants.To date,it was the first report for the two mutations in the GAA gene in the Mainland China.The mutation c.1822C＞T had been reported to be pathogenic,and the latter one,c.2297A＞C,was a new mutation.Conclusions The compound heterozygous c.1822C＞T and c.2297A＞C mutations in GAA gene caused the classic infantile Pompe disease characterized by hypertrophic cardiomyopathy.Determination of GAA activity in peripheral leukocytes and GAA gene sequencing were effective and feasible methods for the diagnosis ofGSD Ⅱ.

目的 探讨长链非编码RNA(long no-coding RNA,LncRNA)心肌梗死相关转录本(myocardial infarction association tran-script,MIAT)基因启动子单核苷酸多态性(single nucleotide polymorphisms,SNPs)与高血压(hypertension,HT)的相关性.方法 采用PCR和Sanger基因测序法检测MIAT基因启动子SNPs;卡方检验对59例HT患者和135例健康对照人群的SNPs进行分型和关联分析.结果 在MIAT基因启动子中共发现7个SNPs,其中rs150465374能增加HT的易感性(P=0.02).结论 MIAT基因启动子多态位点(rs150465374)与HT的发生密切相关.

The GATA transcription factor family consists of six members, GATA1 through GATA6, which play important roles in the regulation of cell growth and differentiation, cell survival, and maintenance of body functions. Current studies regarding GATA6 transcription factor confirm that GATA6 plays a crucial role in the differentiation, development, and function of the human heart. Genetic mutations of GATA6 are associated with a variety of congenital heart diseases, dysfunction of the cardiac conduction system causing various arrhythmias, coronary artery disease, and dilated and hypertrophic cardiomyopathies. The relationship between GATA6 and the human heart is also impacted by multiple other genes and interactions in the body. In this review, we summarize the research and current knowledge of the GATA6 transcription factor related to the human heart and multiple pathologies which provides understanding of its genetic basis to enable future personalized gene therapy and to promote the development and incorporation of basic research into clinical medicine.

目的 探讨GATA6基因启动区-493(rs144923558) G/A、-172(rs 146748749) G/A 2个位点单核苷酸多态性(SNP)与急性心肌梗死(AMI)之间的关系及其相关的危险因素.方法 采用病例-对照研究方法,收集328例AMI患者和344例正常对照;应用聚合酶链反应-限制性内切酶片段长度多态性技术结合DNA测序后的序列比对进行数据统计;运用Hardy-Weinberg平衡检验后,应用x2检验进行相关分析;利用Logistic回归对多种危险因素以及2个SNP位点与AMI发病进行关联性分析;利用Haplovview4.2软件和SHEsis网站进行连锁不平衡及单倍体分析.结果 2个SNP位点共检测出3种基因型为GG、GA和AA,其基因型分布均符合Hardy-Weinberg平衡(P＞0.05),同时在AMI组与对照组间差异无显著性(P＞0.05).多因素Logistic回归分析:增龄、高血压痛、吸烟、低密度脂蛋白胆固醇(LDLC)和甘油三酯(TG)升高是AMI发病的独立危险因素(P＜0.05),HDLC为保护因素(P＜0.05).在显性、隐性和加性3种不同遗传模式下进行Logistic回归分析发现,2个SNP位点与AMI发病无关联性.进行连锁不平衡和单倍型分析提示,该2个SNP位点处于同一个连锁不平衡区域(D'=1.000,r2=1.000),单倍型GG和AA均未增加AMI易感性(P＞0.05).结论 GATA6基因启动区-493(rs144923558) G/A与-172(rs146748749) G/A两个SNP位点为完全连锁不平衡,其中GG为主要单倍型.该2个SNP位点及其单倍体型与AMI发病无相关性,但提供了GATA6基因启动区多态性的群体遗传学资料.

目的 研究肺腺癌转移相关转录因子(MALAT)1对心肌细胞凋亡的影响和机制.方法 使用过氧化氢(H2 O2)处理心肌细胞,Realtime PCR方法检测MALAT1表达差异.在心肌细胞中转染MALAT1 siRNA,流式细胞术测定细胞凋亡,试剂盒测定超氧化物歧化物酶(SOD)和丙二醛(MDA)水平.预测MALAT1与miR-200a有互补结合位点,用荧光素酶报告系统鉴定靶向关系.在心肌细胞中共转染MALAT1 siRNA和miR-200a inhibitor,用上述方法检测其对H2 O2条件下心肌细胞凋亡和SOD、MDA的影响.结果 H2 O2处理后心肌细胞中MALAT1表达水平升高.MALAT1 siRNA抑制H2 O2条件下心肌细胞中MALAT1表达.MALAT1 siRNA抑制H2 O2诱导的心肌细胞凋亡和MDA含量升高,提高细胞中SOD活性.MAL-AT1靶向负调控miR-200a表达.miR-200a inhibitor可逆转MALAT1 siRNA对心肌细胞凋亡和MDA合成抑制作用,降低SOD活性.结论 抑制MALAT1靶向促进miR-200a表达,减少H2 O2诱导的心肌细胞凋亡和氧化损伤.