Array comparative genomic hybridization identifies a heterozygous deletion of exon 3 of the RYR2 gene

Background

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a heritable cardiac disorder characterized by life-threatening ventricular tachycardia caused by exercise or acute emotional stress. The standard diagnostic screening involves Sanger-based sequencing of 45 of the 105 translated exons of the RYR2 gene, and copy number changes of a limited number of exons that are detected using multiplex ligation-dependent probe amplification (MLPA).

Methods

In the current study, a previously validated bespoke array comparative genomic hybridization (aCGH) technique was used to detect copy number changes in the RYR2 gene in a 43-year-old woman clinically diagnosed with CPVT.

Results

The CGH array detected a 1.1 kb deletion encompassing exon 3 of the RYR2 gene. This is the first report using the aCGH technique to screen for mutations causing CPVT.

Conclusions

The aCGH method offers significant advantages over MLPA in genetic screening for heritable cardiac disorders.     

应用MLPA技术和aCGH技术检测额外小标记染色体

目的:应用多重连接依赖探针扩增(multiplex ligation-dependent probe amplication,MLPA)技术和微阵列比较基因组杂交(array comparative genomic hybridization,aCGH)技术检测1例额外小标记染色体?方法:应用MLPA技术对外周血G显带诊断的1例智力低下患儿携带小标记染色体(染色体核型为47,XY,+Mar)进行分析,确定小标记染色体的来源,并进一步通过aCGH技术对患儿进行全基因组高分辨率扫描确定小标记染色体的大小及具体来源区域?结果:MLPA分析结果显示患儿18号染色体p11.21和p11.32两个区域探针信号高于正常值范围,提示这两个区域存在拷贝数的增加;aCGH分析结果显示拷贝数增加的区域为p11.21~p11.32,范围约为15 Mb?两项技术分析结果均证实额外小标记染色体来源于18号短臂,即该患儿为18p三体?结论:应用MLPA技术和aCGH技术可确定额外小标记染色体的来源,并能明确其来源染色体的具体区域范围,从而为判断标记染色体的遗传学效应提供帮助     

A study on protective action of Astragalus Injection()in ouabain-induced cardiac Toxicity of guinea pigs)in ouabain-induced cardiac Toxicity of guinea pigs

Objective: To study the protective action of Astragalus Injection (AI) on ouabain-induced cardiac toxicity.Methods: Forty guinea-pigs were randomly divided into the AI group and the control group, AI injected intravenously in the AI group and 0.9% normal saline injected in the control group, ouabain was injected in contralateral of both groups intravenously 8 mins later. The time of cardiac ventricular tachycardia (VT) and cardiac ventricular fibrillation (VF), and the dose of ouabain were documented.Results: Compared with the control group AI could markedly prolong the time of VT and VF, and increase the dose of ouabain induces VT and VF (P < 0.01).Conclusion: AI decreases the incidence of digitalism. This subject is supported by the Scientific Research Fund of Guangzhou University of Traditional Chinese Medicine and Pharmacology (No. 9764)     

达格列净联合左西孟旦治疗慢性心力衰竭患者伴心律失常的疗效及安全性分析

目的 探讨达格列净联合左西孟旦治疗慢性心力衰竭（CHF）伴心律失常的疗效及安全性。方法选取2021年3月—2023年3月滕州市中心人民医院收治的192例CHF伴心律失常患者,采用随机数字表法分为对照组和研究组,每组96例（研究组最终脱落3例,对照组脱落2例）。对照组给予左西孟旦注射液,研究组在对照组的基础上给予达格列净片。两组持续治疗1个月后观察疗效。比较两组临床疗效、室性心律失常、心功能、心肌损伤指标及药物不良反应发生情况,对比两组治疗后30 d内因心力衰竭再住院情况。结果 研究组总有效率高于对照组（P <0.05）。研究组治疗前后室性早搏、成对室性早搏、短阵室速发作次数的差值高于对照组（P <0.05）。研究组治疗前后左心室射血分数、左室舒张末期内径、左心室收缩末期内径的差值高于对照组（P <0.05）。研究组治疗前后N末端脑钠肽前体、心肌肌钙蛋白Ⅰ的差值高于对照组（P <0.05）。两组总药物不良反应发生率、治疗后30 d内因心力衰竭再住院率比较,差异均无统计学意义（P>0.05）。结论 达格列净联合左西孟旦治疗CHF伴心律失常患者可增强临床疗效,减...     

Multiplex ligation-dependent probe amplification for rapid detection of deletions and duplications in the dystrophin gene

Objective：Duchenne muscular dystrophy （DMD） and Becker muscular dystrophy （BMD） are X-linked disorders caused by mutations in the dystrophin gene. The majority of recognized mutations are copy number changes of individual exons. The objective of the present study was to assess the multiplex ligation-dependent probe amplification （MLPA） effects of detection of gene mutations. Methods： Samples of 20 control males and 80 males and their mothers referred to our diagnostic facility on the clinical suspi- cion of DMD or BMD were tested by MLPA and multiplex PCR. Results ： The mean DQs for all peak of 20 control male samples was 1.02 （range from 0.83 to 1.21） by MLPA. Deletions or duplications were iden- tified in 6 out of 31 families that had been previously tested as negative by multiplex PCR. One case of complex rearrangement involving a duplication of two regions： dupEX3-9 and dupEX 17-41 were found by MLPA. Conclusions： MLPA is a highly sensitive method and rapid alternative to multiplex PCR for detec- tion of DMD and BMD.     

Ruling out cardiac failure: Cost-benefit analysis of a sequential testing strategy with NT-proBNP before echocardiography

Abstract

Objectives. To estimate the possible economic benefit of a sequential testing strategy with NT-proBNP to reduce the number of echocardiographies.

Methods. Retrospective study in a third-party payer perspective. The costs were calculated from three Swedish counties: Blekinge, Östergötland, and Uppland. Two cut-off levels of NT-proBNP were used: 400 and 300 pg/mL. The cost-effectiveness of the testing strategy was estimated through the short-term cost avoidance and reduction in demand for echocardiographies.

Results. The estimated costs for NT-proBNP tests and echocardiographies per county were reduced by 33%–36% with the 400 pg/mL cut-off and by 28%–29% with the 300 pg/mL cut-off. This corresponded to a yearly cost reduction of approximately €2–5 million per million inhabitants in these counties.

Conclusion. The use of NT-proBNP as a screening test could substantially reduce the number of echocardiographies in the diagnostic work-up of patients with suspected cardiac failure, as well as the associated costs.     

Can costs of screening for hypertension and diabetes in dental care and follow-up in primary health care be predicted?

Abstract

Aim. The purpose was to assess the direct costs of screening for high blood pressure and blood glucose in dental care and of follow-up in primary health care and, based on these data, arrive at a prediction function.

Study population. All subjects coming for routine check-ups at three dental health clinics were invited to have blood pressure or blood glucose measurements; 1,623 agreed to participate. Subjects screening positive were referred to their primary health care centres for follow-up.

Methods. Information on individual screening time was registered during the screening process, and information on accountable time, costs for the screening staff, overhead costs, and analysis costs for the screening was obtained from the participating dental clinics. The corresponding items in primary care, i.e. consultation time, number of follow-up appointments, accountable time, costs for the follow-up staff, overhead costs, and analysis costs during follow-up were obtained from the primary health care centres.

Results. The total screening costs per screened subject ranged from €7.4 to €9.2 depending on subgroups, corresponding to 16.7–42.7 staff minutes. The corresponding follow-up costs were €57–€91. The total resource used for screening and follow-up per diagnosis was 563–3,137 staff minutes. There was a strong relationship between resource use and numbers needed to screen (NNS) to find one diagnosis (P < 0.0001, degree of explanation 99%).

Conclusions. Screening and follow-up costs were moderate and appear to be lower for combined screening of blood pressure and blood glucose than for separate screening. There was a strong relationship between resource use and NNS.     

基于CRISPR/Cas9系统定点编辑小鼠MAD2L1基因及其脱靶效应分析

目的 建立利用CRISPR/Cas9系统对小鼠MAD2L1基因第二外显子基因编辑的方法体系，并分析CRISPR/Cas9对MAD2L1基因编辑的脱靶效应。方法 通过CHOPCHOP网站设计位于小鼠MAD2L1基因第二外显子的靶点序列，并构建Cas9-MAD2L1载体，将该载体转染到NIH/3T3细胞中，通过嘌呤霉素筛选并结合荧光显微镜观察GFP后，提取细胞转染后的基因组DNA，利用PCR方法，结合T7E1分析和桑格尔测序，鉴定对小鼠MAD2L1基因编辑情况，并对转染后的NIH/3T3细胞进行CRISPR/Cas9脱靶效应分析。结果 将Cas9-MAD2L1载体转染到NIH/3T3细胞并进行嘌呤霉素筛选后，荧光显微镜下观察到大量表达GFP的细胞，PCR结合T7E1结果显示，以转染后的细胞DNA为模板扩增出的228 bp MAD2L1 PCR产物，可被酶切成166 bp和62 bp片段，测序结果显示，成功对MAD2L1基因第二外显子靶点处进行基因编辑，脱靶效应分析未检测到CRISPR/Cas9有对脱靶位点进行基因编辑。结论 成功建立对小鼠MAD2L1基因第二外显子进行基因编辑的方法体系，设计的对MAD2L1基因编辑靶点未检测到脱靶效应的发生。     

Impedance cardiographic hemodynamic variables and hypertension in elderly Han residents

Abstract

Objective. We studied the relationship between systolic blood pressure and hemodynamics using impedance cardiography in elderly Han residents in order to evaluate how different hemodynamic variables are altered with normal aging and with hypertension superimposed on aging.

Methods. A total of 670 subjects, aged 60–93 years, were evaluated with impedance cardiography for non-invasive hemodynamic variables. The subjects were categorized as hypertensives or normotensives, and then they were also divided into six subgroups according to actual systolic blood pressure values.

Results. Hypertensive patients had significantly lower values of cardiac output (4.4 ± 1.5 L/min) and cardiac index (2.6 ± 1.0 L/min/m²) than those in the normotensive group (4.7 ± 1.5 L/min, and 2.8 ± 0.8 L/min/m², respectively; P < 0.05 for both). Compared to the normotensive group, stroke volume and stroke index values were also lower and systemic vascular resistance and systemic vascular resistance index were higher in the hypertensive group. There were no significant differences in left ventricular stroke work and left ventricular stroke work index between the two groups. When all 670 subjects were stratified to actual blood pressure, cardiac output of group 6 patients (systolic blood pressure ≥180 mmHg) was 19% lower than that of group 1 subjects (SBP <140 mmHg; P < 0.05). Similarly, systemic vascular resistance of group 6 patients was 56% higher than that of group 1 subjects (P < 0.05).

Conclusion. With aging, arterial systolic blood pressure is elevated as a result of increased arterial stiffness and increased systemic vascular resistance. With hypertension, these values are further elevated. Non-invasive impedance cardiography helps to characterize the hemodynamic mechanisms, which can improve hypertension management.     

四腔心切面及三血管气管切面在中孕早期胎儿心脏快速筛查中的应用

目的 探讨四腔心切面及三血管气管切面在中孕早期胎儿心脏快速筛查中的应用价值。方法 回顾性分析重庆市人口和计划生育科学技术研究院附属医院2010年1月至2014年12月25 463例14～18周胎儿心脏超声检查结果。结果 共检出胎儿心脏异常51例：单心室和/或单心房15例,永存动脉干6例,大动脉转位5例,右位主动脉弓9例,右室双出口8例,主动脉弓离断1例,法洛四联症4例,永存左上腔静脉3例;误诊1例主动脉明显狭窄为永存动脉干,漏诊2例轻型法洛四联症及8例室间隔缺损。结论 四腔心切面及三血管气管切面在中孕早期胎儿心脏筛查中可以为心脏重大畸形提供重要线索。     

肾去交感神经术对慢性心力衰竭大鼠心肌纤维化及结缔组织生长因子表达的影响

目的 观察肾去交感神经术(renal sympathetic denervation,RDN)对心力衰竭大鼠心肌纤维化及心肌组织中结缔组织生长因子(connective tissue growth factor,CTGF)表达的影响,探讨肾去交感神经术治疗心力衰竭的机制。方法 48只SPF级Wistar雄性大鼠分成4组,分别为心力衰竭RDN治疗组(RDN+HF组)、心力衰竭模型组(Sham+HF组)、假手术组(Sham组)及正常对照组,其中RDN+HF组和Sham+HF组分别进行双侧肾交感神经切除或假手术处后用异丙肾上腺素(isoproterenol,ISO)诱导建立大鼠心力衰竭模型,4周后行心脏彩超测左心室舒张末期内径(LVEDD)、舒张末期容积(LVEDV)、左心室射血分数(EF%)及收缩百分率(FS%)评估心功能变化并处死大鼠,留取心脏左心室心肌组织行Masson染色测定心肌胶原容积分数(CVF);免疫组化法检测心肌组织CTGF蛋白表达,RT-qPCR检测左心室心肌CTGFmRNA。结果 与心力衰竭模型组相比,心力衰竭RDN治疗组中反映心室腔扩大的指标LVEDD和LVEDV(LVEDD:0.65±0.02 vs 0.76±0.04,P<0.05;LVEDV:0.77±0.05 vs 0.91±0.04,P<0.05)均明显减小,反映心肌收缩力的指标EF和FS(EF:72.66%±2.82% vs 64.21%±2.50%,P<0.05;FS:32.55%±2.95% vs 25.88%±3.42%, P<0.05)均明显增大,反映胶原含量的指标CVF(13.96%±2.90% vs 59.69%±4.93%,P<0.05)下降,CTGF蛋白表达(4.53±0.75 vs 7.06±0.72, P<0.05)和mRNA相对量(6.95±0.73 vs 10.88±0.85, P<0.05)均减少,但仍高于假手术组(P均<0.05)。结论 肾去交感神经术能够改善心力衰竭大鼠心功能并抑制心肌纤维化的进展,其机制可能与下调CTGF的表达有关。     

Screening of pathogenic genes in Chinese patients with arrhythmogenic right ventricular cardiomyopathy

Background Arrhythmogenic right ventricular cardiomyopathy （ARVC） is a heritable cardiac disease predominantly caused by mutations in desmosomal protein genes. Previous genetic analyses of the Chinese ARVC population are limited to small size and restriction to a single gene. This study was aimed to investigate the genotype in a large series of Chinese patients with ARVC through comprehensively screening nine ARVC-causing genes. Methods A total of 100 unrelated ARVC patients and 300 age, gender and ethnicity matched healthy controls were genetically tested with multiplexing targeted resequencing for nine previously reported ARVC-causing genes, including plakophilin-2, desmoplakin, desmoglein-2, desmocollin-2, plakoglobin, transforming growth factor beta-3, transmembrane protein 43, desmin and Lamin A/C. Results Fifty-nine mutations were identified in 64% of the patients, among which, 93% were located in desmosomal protein genes. Plakophilin-2 mutations accounted for 54% of the total and 58% of the desmosomal mutations, with a truncating mutation type making up about 2/3 of the plakophilin-2 mutations. Only four mutations were found in nondesmosomal genes; two in transmembrane protein 43 and two in transforming growth factor beta-3. Two of them （one of each gene） appeared as single missense mutations. No mutation was identified in desmin or Lamin A/C. Multiple mutations were found in 23% of the patients, with plakophilin-2 being found in 57% of the multi-mutation carriers. Conclusions Plakophilin-2 was the most common gene mutation that was identified in Chinese ARVC patients. Nondesmosomal genes should be added to desmosomal protein genes when performing molecular genetic screening in patients with suspected ARVC.     

Closed-Chest Massage: An Effective Resuscitative Procedure for the Maintenance of the Circulation During Cardiac Arrest

Reports of clinical benefits of closed-chest cardiac resuscitation refute recently published studies contesting its effectiveness.

Our experimental investigations demonstrate that closed-chest massage is able to achieve adequate cerebral circulation and oxygenation during cardiac arrest.

Clinical studies indicate that a significant number of coronary patients can be saved if a monitor system is used to warn of the onset of ventricular fibrillation or arrest. To be successful, closed-chest resuscitation must be instituted within the four-minute limit after onset of cardiac arrest. When ventricular fibrillation occurs, electrical countershock is usually obligatory. Cardiac pacemaking is a specific necessity for patients with ventricular arrest.

     

MLPA和多重PCR法检测假肥大性肌营养不良患者DMD基因

目的 应用多重连接依赖式探针扩增 (MLPA)和多重PCR法对临床诊断为假肥大性肌营养不良患者进行基因诊断,并比较两种方法检测DMD基因缺失和重复改变的效果。方法 选择2005年至2007年在中国医科大学盛京医院儿科就诊的51例DMD患者和8例BMD患者。采用MLPA法对经多重PCR法检测过的患者的DMD基因的缺失/重复突变进行突变筛查,同时对先证者的母亲进行基因的缺失/重复突变检测。结果 用多重PCR方法在59例假肥大性肌营养不良症患者中检测到31例患者有外显子缺失。MLPA检测出33例外显子缺失,6例外显子重复和1例点突变,同时检测出26例患儿的母亲为携带者。MLPA比多重PCR多检测出10例DMD基因突变,两种方法共同检测出的30例突变中MLPA 检测出16例基因突变范围比多重PCR大。结论 与多重PCR法相比,MLPA更加简便、快捷、可靠,同时可以对携带者进行诊断,是一种高效的遗传病基因诊断手段。 【关键词】假肥大性肌营养不良症;多重连接依赖式探针扩增;多重PCR;缺失/重复突变     

度洛西汀对大鼠心肌缺血再灌注心律失常的影响及机制

目的 探讨度洛西汀对大鼠心脏缺血再灌注心律失常的影响及机制。方法 30只Sprague Dawley（SD）大鼠随机分为假手术组（Sham组）、缺血再灌注组（IR组）和度洛西汀组（Dulo组）。IR组大鼠左前降支结扎30min后再灌注120min,Dulo组大鼠结扎左前降支30min前腹腔注射盐酸度洛西汀40mg/kg,之后处理同IR组,Sham组仅暴露左前降支,未行结扎。二导联心电监测并记录3组心律失常发生情况,应用LabChart8软件分析心电图参数。Triphenyltetrazolium chloride（TTC）染色对比IR组及Dulo组大鼠心肌梗死面积。蛋白免疫印迹试验检测各组心脏组织Akt、细胞外调节蛋白激酶（extracellular regulated protein kinases,Erk）、caspase-3、超氧化物歧化酶（superoxide dismutase,SOD）1、SOD2和连接蛋白43（connexin 43,Cx 43）蛋白改变。结果 与IR组比较,缺血期Dulo组大鼠室性期前收缩次数和室性心动过速次数减少（P<0.05）;再灌注期Dulo组的室性心动过速减少（P<0.05）,室性期前收缩次数差异无统计学意义（P>0.05）。度洛西汀抑制缺血和再灌注所致校正后Q-T间期（QTc）的延长（P<0.05）,并减小心肌梗死面积（P<0.05）。度洛西汀抑制Akt和Erk蛋白的磷酸化,减少cleaved caspase-3、cytochrome C蛋白表达并增加SOD1、SOD2和Cx43蛋白表达。结论 度洛西汀降低Akt和Erk蛋白磷酸化,抑制氧化应激及细胞凋亡,减低心脏缺血再灌注损伤过程中室性心律失常发生,减少梗死面积。     

Phospholamban Antisense RNA Improves SR Ca2+-ATPase Activity and Left Ventricular Function in STZ-induced Diabetic Rats

ObjectiveTo study the effect of phospholamban antisense RNA (asPLB) on sarcoplasmic reticulum Ca²⁺-ATPase activity and cardiac function in rats with diabetes mellitus (DM) mediated by recombinant adeno-associated virus (rAAV) vector.MethodsSix weeks after the induction of DM by streptozotocin injected intraperitoneally, the rats were divided into three groups, namely: DM-rAAV-asPLB group, DM-saline group and DM group (control group). The rats in the DM-rAAV-asPLB group were intramyocardially injected with rAAV-asPLB, the rats in the DM-saline group were injected with saline, and those in the control group did not receive any treatment. Six weeks after gene transfer, the expressions of PLB protein and PLB phosphorylation were detected by Western-blot, while the activity of sarcoplasmic reticulum (SR) Ca²⁺-ATPase and left ventricular function were measured.ResultsThe PLB protein expression level was significantly higher whereas the PLB phosphorylation, SR Ca²⁺-ATPase activity and left ventricular function were significantly lower in the DM-saline group than in the control group. No significant difference was found in PLB protein expression level, PLB phosphorylation or SR Ca²⁺-ATPase activity between the DM-rAAV-asPLB group and the control group. The left ventricular function in the DM-rAAV-asPLB group was poorer than in the control group and was better than in the DM-saline group.ConclusionrAAV-asPLB can down-regulate PLB protein expression and up-regulate PLB phosphorylation and SR Ca²⁺-ATPase activity, thus contributing to the improvement of in vivo left ventricular function.     

下调心肌CPT1b的表达对肥胖小鼠心肌细胞钙调控的影响

目的 研究干扰心肌组织中肉毒碱脂酰转移酶-1b（CPT1b）的表达对高脂饮食诱导的肥胖小鼠心肌细胞钙调控的影响。方法 4周龄的雄性C57小鼠,随机分为正常对照组（N-mock）、肥胖对照组（O-mock）及肥胖干预组（O-CPT1b）,采用高脂饮食诱导肥胖。6周龄时,经心肌分别注射靶向CPT1b（O-CPT1b）或靶向无关基因（N-mock、O-mock）的重组慢病毒,以下调目标基因的表达。10周后,取小鼠左心室组织检测RNA干扰的效率;采用Western blot法检测左心室组织中肌浆网钙泵（SERCA2a）的蛋白表达;并分离单个心室肌细胞,使用活细胞工作站检测心肌细胞钙瞬变。结果 肥胖小鼠心肌组织中CPT1b的表达增加,慢病毒介导的RNA干扰显著下调其表达。肥胖引起心肌细胞SERCA2a的蛋白表达降低及肌质网钙处理能力的下降,下调CPT1b的表达增加了SERCA2a的含量,并改善了钙调控异常。结论 下调心肌组织中CPT1b的表达可改善肥胖所导致的心肌细胞钙调控异常。     

Marshall韧带消融对心肌不应期和心肌梗死后室性心律失常的影响

目的 研究Marshall韧带消融对心肌有效不应期和室性心律失常的影响。方法 21只杂种犬随机分为Marshall韧带消融组（n=11）和对照组（n=10）。记录左、右心房和左、右心室不同部位的电图,并测量各部位有效不应期（effective refractory period,ERP）,计算ERP的空间离散度。消融组实验犬采用大头电极对Marshall韧带进行消融,消融后再次测量ERP,计算ERP离散度。对照组犬不行消融。测量结束后,结扎冠状动脉左前降支,持续体表心电图记录1h,记录室性心律失常发生情况。结果 与基础状态相比,Marshall韧带消融后左、右心室和右心房的ERP显著延长,左心房的ERP变化不显著,心房和心室的ERP离散度在消融前后无显著差异。结扎冠脉左前降支后,消融组的室性期前收缩数和室性心动过速阵数显著低于对照组,消融组的心室颤动和室性心动过速发生率与对照组差异无统计学意义（P>0.05）。结论 Marshall韧带消融可延长犬左、右心室和右心房的ERP,而对ERP离散度无显著影响。Marshall韧带消融对心肌梗死后室性心律失常的发生可能有保护作用。     

骨内单次注射小剂量辛伐他汀对大鼠心梗后血管新生的影响

目的 研究骨内局部单次注射小剂量辛伐他汀对大鼠心梗后血管新生和心功能的影响。方法 Wistar大鼠随机分为假手术组、心肌梗死模型组和骨内注射辛伐他汀组（n=12）。冠状动脉左前降支结扎建立大鼠心肌梗死模型。24 h后实验组左胫骨内单次注射辛伐他汀0.5 mg,4周后分别通过小动物超声心动图评价左室功能,三苯基氯化四氮唑（TTC）染色计算心肌梗死面积,免疫荧光染色检测局部血管新生情况。结果 超声心动图结果表明心肌梗死4周后左心室收缩功能明显下降,骨内注射辛伐他汀对大鼠心肌梗死后左心室功能未见明显改善;TTC染色发现骨内注射辛伐他汀组心肌梗死面积未见明显减少;免疫荧光染色显示,骨内注射辛伐他汀组心肌血管密度没有显著增加。结论 大鼠心梗24 h后骨内单次注射小剂量辛伐他汀（0.5 mg）,心肌梗死面积、血管新生及心脏功能无显著改善。     

干扰CD36的表达对高脂饮食诱导的肥胖小鼠心肌细胞钙调控的影响

目的 研究干扰心肌组织中脂肪酸转位酶CD36的表达对高脂饮食诱导的肥胖小鼠心肌细胞钙调控的影响。方法 4周龄的雄性C57小鼠,随机分为正常对照组（N-mock）、肥胖对照组（O-mock）及肥胖干预组（O-CD36）,采用高脂饮食诱导肥胖。6周龄时,经心肌注射靶向CD36（O-CD36）或靶向无关基因（N-mock、O-mock）的重组慢病毒,以下调心肌组织中目标基因的表达。16周龄时,取小鼠左心室组织,检测CD36和肌质网钙泵（SERCA2a）的mRNA和蛋白表达;并分离单个心室肌细胞,使用活细胞工作站检测心肌细胞钙瞬变。结果 肥胖小鼠心肌组织中CD36的表达较正常小鼠无显著改变,慢病毒介导的RNA干扰显著下调了CD36的表达。肥胖引起心肌细胞SERCA2a的蛋白表达降低及肌质网钙处理能力的下降;下调CD36的表达增加了SERCA2a的含量,并改善了钙调控异常。结论 下调心肌组织中CD36的表达可改善肥胖所引起的心肌细胞钙调控异常。