大鼠急性心肌缺血后肌浆网RyR2 mRNA表达变化

目的 研究大鼠急性心肌缺血后心肌肌浆网兰尼碱受体蛋白2(ryanodine receptor 2,RyR2)mRNA表达的变化.方法 将SD大鼠分为正常对照组、心肌缺血组和缺血性猝死组.采用腹腔注射垂体后叶素的方法复制大鼠急性心肌缺血和猝死模型,对心肌进行半定量荧光RT-PCR检测,观察RyR2 mRNA表达水平的变化.结果 与正常对照组相比,不同时间和不同程度的急性心肌缺血后心肌肌浆网RyR2 mRNA表达均显著降低(P<0.05).结论 心肌缺血性损伤可诱导心肌钙调控蛋白RyR2 mRNA表达下调.     

窖蛋白与不明原因心源性猝死的相关性研究进展

不明原因心源性猝死(unexpected sudden cardiac death,USCD)因其不伴有心脏结构的异常,尸体解剖呈阴性改变,一直是法医病理学鉴定的热点难题。USCD可能与部分致死性心律失常有关,该类心律失常多由心脏离子通道蛋白或其相关蛋白发生异常所致。窖蛋白可以通过其脚手架区域与多种心肌离子通道蛋白结合,在维持心肌动作电位的去极化和复极化中起到关键作用。当窖蛋白由于基因突变或蛋白表达异常等因素导致其结构和功能受到影响时,受其调控的心肌离子通道的功能也受到损害,继而引起多种离子通道病的发生,出现心律失常甚至心源性猝死。研究窖蛋白对离子通道功能的影响对于探索恶性心律失常及心源性猝死的发生机制具有重要意义。     

心脏性猝死心肌组织N-Cadherin、Bax表达变化及评价

目的观察心脏性猝死者(SCD)心肌组织的神经性钙粘附蛋白(N-Cadherin)和Bax的表达变化,探讨其法医学意义。方法分别选取心脏性猝死和排除心脏疾病死因的尸检案例心肌组织标本各33例、29为SCD组和对照组。光镜下观察心肌组织病理学改变,检测N-Cadherin和Bax在心肌组织中的表达变化,并进行统计学分析。结果 N-Cadherin在SCD组心肌中表达呈弱阳性,排列紊乱,显著低于正常心肌,正常心肌组织中N-Cadherin呈强阳性表达,细胞间界限明显,排列整齐。Bax在SCD组表达呈阳性,显著高于正常心肌。结论 N-Cadherin和Bax的变化表达对心脏性猝死鉴定有意义。     

NUP155与房颤及原发性心律失常性猝死关系的研究进展

NUP155是组成核孔复合体的一种重要的核孔蛋白,在核孔复合体介导大分子物质出入细胞核过程中发挥重要作用。原发性心律失常是导致猝死的重要原因之一,其主要由于编码心肌细胞膜上离子通道的基因突变所致,因此又被称为"心脏离子通道病"。NUP155是第一个被发现突变后能导致原发性心律失常及心源性猝死的非离子通道基因。本文将对NUP155的结构和生物学功能及其与原发性心律失常性猝死的关系进行阐述。     

窦房结病理性纤维化的研究进展

人类心脏节律主要受窦房结调控,纤维化对窦房结起搏复合体的结构和功能完整性有重要调节作用。在生理状态下,窦房结中纤维化的量与心率呈负相关,与年龄、心脏大小呈正相关,并可维持心率相对稳定。窦房结病理性纤维化可能导致不同类型的心律失常引起猝死。明确窦房结病理性纤维化相关机制将为临床治疗窦房结纤维化提供靶点,也可为法医病理学工作者提供诊断依据。本文回顾了窦房结病理性纤维化的主要机制,包括窦房结内心脏成纤维细胞异常激活、心外膜脂肪组织增生、钙钟紊乱、血管狭窄等,介绍其检验方法、诊断标准及在心脏性猝死中的作用,探讨其潜在的应用领域,为相关研究、应用提供参考。     

TGF-β1在SCN5A基因变异所致心源性猝死中调控作用

SCN5A基因变异所致心源性猝死发生机制尚不清楚。目前研究显示TGF-β1介导心肌纤维化以及离子通道重构调节机制的异常可能是SCN5A基因变异导致SUNDS发生的主要原因。本文就转化生长因子β1对SCN5A基因变异所致心源性猝死调控的影响机制研究进展进行综述,以期为心源性猝死法医学研究和实践提供参考。     

兰尼碱受体及其法医学意义

兰尼碱受体是心肌细胞内的钙释放通道。在心脏缺血或肥大等病理过程中兰尼碱受体的功能和数量也会发生明显变化,从而导致心肌细胞处理细胞内钙离子的能力下降或细胞内钙超载,触发致死性的室性心律失常,诱发心源性猝死。     

Zif/268免疫组化在心性猝死诊断中的应用研究

目的　观察猝死和非猝死组尸检心脏标本心肌局部Zif/2 68的表达 ,为心肌早期缺血死后诊断提供客观指标。　方法　采用免疫组化SABC法和图像分析与统计学处理系统 ,对 18例猝死和 18例非猝死组尸检心脏标本心肌局部细胞核蛋白Zif/2 68的累积情况进行研究。　结果　 18例心性猝死心脏标本心肌局部有部分心肌细胞核呈阳性着色 ,阳性表达率达 10 0 %。 18例对照组标本仅 2例心肌细胞核散在阳性。图像定量分析结果显示两组差异显著。　结论　说明免疫组化染色法检测心肌细胞核Zif/2 68的表达有望成为急性心肌缺血死后诊断的一种有价值有意义的手段。     

Zif/268免疫组化在心性猝死诊断中的应用研究

目的 观察猝死和非猝死组尸检心脏标本心肌局部Zif／268的表达，为心肌早期缺血死后诊断提供客观指标。方法 采用免疫组化SABC法和图像分析与统计学处理系统，对18例猝死和18例非猝死组尸检心脏标本心肌局部细胞核蛋白Zif／268的累积情况进行研究。结果 18例心性猝死心脏标本心肌局部有部分心肌细胞核呈阳性着色，阳性表达率达100％。18例对照组标本仅2例心肌细胞核散在阳性。图像定量分析结果显示两组差异显著。结论 说明免疫组化染色法检测心肌细胞核Zif／268的表达有望成为急性心肌缺血死后诊断的一种有价值有意义的手段。     

致心律失常性右室心肌病的研究进展

致心律失常性右室心肌病(ARVC)是一种原发性心肌病,其特征性病理改变为心肌细胞变性退化被纤维脂肪组织所替代,最终导致心力衰竭,心律失常,猝死。ARVC是目前青年人及运动员猝死的主要死因之一,其发病率约为1/1000-1/5000,男性较女性多见.近年来越来越多研究表明ARVC与基因突变相关,尤其是编码桥粒蛋白基因,但具体发病机制仍不明确。     

Genetic variability of RyR2 and CASQ2 genes in an Asian population

We analyzed the coding regions of the cardiac calcium-handling genes, ryanodine receptor 2 (RyR2) and calsequestrin 2 (CASQ2) for genetic variants in a healthy Chinese population (n = 95) and in a cohort of 28 sudden unexplained death victims. Mutations in RyR2 and CASQ2 have been shown to alter calcium homeostasis during excitation–contraction coupling and predispose individuals to fatal cardiac arrhythmias. The genetic screening was accomplished by denaturing high-performance liquid chromatography and DNA sequencing methods. Genetic analysis revealed the following non-synonymous genetic variations: two reported RyR2 polymorphisms; 5654G>A (G1885E) and 5656G>A (G1886S), two reported CASQ2 polymorphisms; 196A>G (T66A) and 226G>A (V76M) and one novel CASQ2 mutation; 529G>C (E177Q). The functional significance of the novel CASQ2 mutation has not been evaluated and characterized. This study shows that multiple genetic variations of the RyR2 and CASQ2 genes exist in the two study populations. The inter-individual genetic variability may underlie the different susceptibility of individuals to developing ventricular tachycardia. The research results will be valuable for which future work involving clinical and forensic samples can be based upon to distinguish potential disease-associated mutations from common polymorphisms.     

全外显子组测序对肥厚型心肌病猝死者的基因分析

目的在全外显子组水平分析1例肥厚型心肌病(hypertrophic cardiomyopathy,HCM)猝死病例的相关致病性基因突变。方法对1例具有HCM病理学特征的猝死病例样本,利用Illumina~Hi Seq 2500平台进行全外显子组测序(whole exome sequencing,WES)。测序数据分析以hg19为参照序列,筛选可疑的单核苷酸变异位点,通过PhyloP、PolyPhen-2、SIFT等软件进行突变的保守性和功能分析。结果经过筛选,发现该病例的MYBPC3基因发生C719R杂合突变。结论利用二代测序技术进行全外显子组水平的分子解剖(基因突变检测和分析),有助于明确HCM的分子机制,并为死因分析提供新的方法和思路。     

Sudden Death Caused by Anomalous Origin of the Coronary Artery During Exercise

Anomalous origin of the coronary artery (AOCA) is a rare, but important cause of sudden cardiac death among young athletes. Nine autopsy cases (8 male, 1 female; mean age, 17.9 years; age range, 11–31 years) of sudden death during or just after exercise caused by AOCA were reviewed. The exercises performed at the time of death were running (4 cases), soccer (2 cases), and baseball, swimming and kendo (Japanese swordsmanship) (1 case each). In 6 cases, the left coronary artery arose from the right sinus of Valsalva, and in 3, the right coronary artery from the left sinus. The coronary arteries passed between the pulmonary artery and the aorta with an acute angle takeoff from the orifice. Three cases had cardiovascular manifestations prior to death. In cases with cardiovascular manifestations, novel imaging methods should be considered to prevent sudden death.     

Sudden death due to an unrecognized cardiac hydatid cyst: three medicolegal autopsy cases

Echinococcosis is a human infection caused by the larval stage of Echinococcocus granulosus. The most common sites of infection are the liver and the lungs. Cardiac hydatid cysts are very rare, even in regions where hydatic cysts are endemic (the Mediterranean, South America, Africa, and Australia). It has been reported that cardiac involvement is seen in about 0.5-3% of human echinococcosis cases. Three cases of cardiac hydatid disease that caused sudden death and which were histopathologically diagnosed are reported. Cardiac echinococcosis is rare, but due to its insidious presentation and affinity to cause sudden death, it is important that it be identified in the histopathological examination.     

Commotio Cordis – A Report of Two Similar Cases

Commotio cordis is a rare and fatal mechano‐electric arrhythmogenic syndrome, occurring mainly during sports activities. The present study describes two similar cases of sudden death caused by commotio cordis associated with homicide. The two decedents were both 15‐year‐old male teenagers. Both collapsed within several minutes after being punched in the precordial region, as observed by witnesses at the scenes. Although electrocardiograms were not recorded at the scenes or the hospitals, the sudden onset of cardiovascular, respiratory, and neural symptoms were consistent with sudden cardiac death caused by commotio cordis. Autopsy and forensic morphology both revealed no cardiac or pericardiac structural damage, evident lesions of other internal organs, or underlying diseases, along with negative toxicological analysis, conforming to criteria for diagnosis of commotio cordis. The diagnosis of commotio cordis by forensic pathologists is important in deliberating a verdict of homicide, especially involuntary homicide. In rare instances, a death caused by commotio cordis may have a homicide manner of death.