105例尸体解剖的病理学分析

目的：剖析不明原因死亡的疾病分布及引起死亡的原因。探讨死亡所发生的病理学特点及猝死的发生机制。方法：收集不明原因死亡的尸体解剖材料105例,进行组织病理学检验,部分做了法医学的毒物分析。结果：在105例尸检中,21-40岁青壮年81例,为第一高峰,其中病理性死亡81例,暴力性死亡24例,猝死35例;89.5%找到死亡的主要疾病,疾病的分布以心血管最常见,共22例,其次呼吸系统,中毒,神经系统以及其他疾病。结论：科学准确地进行尸体解剖。不但可明确死因。而且丰富和发展相关临床学科的内容。对提高诊治水平具有重要意义。     

心肌间质脂肪浸润105例临床病理学分析

目的对比研究心肌间质脂肪浸润和致心律失常性右心室心肌病(arrhythmogenic right ventricular cardiomyopathy,ARVC)的病理学特点,探讨其发生发展的相关因素及影响。方法收集105例心肌间质有脂肪无纤维组织浸润病变和6例ARVC的尸检资料,对比二者的病变特点,分析心肌间质脂肪浸润程度与年龄、冠状动脉狭窄程度的相互关系。结果 (1)105例病变表现为心肌间质仅有脂肪组织浸润和渐进的心肌萎缩;6例ARVC特征性的病变是右心室为主的心肌层被广泛的纤维脂肪组织所替代,伴有心肌萎缩或炎细胞浸润。(2)心肌间质脂肪浸润与年龄增长和冠状动脉狭窄程度无关(P0.05)。(3)心肌间质脂肪浸润伴心肌细胞萎缩率为57.14%(60/105),轻度组(7/42,16.67%)与中度组(39/47,82.98%)和重度组(14/16,87.50%)比较差异有统计学意义(P0.01);中度组与重度组比较差异无统计学意义(P0.05)。(4)14例中重度心肌间质脂肪浸润和5例ARVC均表现为心源性猝死。结论人体心肌间质脂肪浸润常常伴有心肌细胞萎缩,其发生发展与年龄增长和冠脉狭窄无关;中重度心肌间质脂肪浸润和ARVC可发生心源性猝死。     

肉芽肿性阿米巴脑炎的临床病理学研究

目的 探讨棘阿米巴属自由生活阿米巴引起的肉芽肿性脑膜脑炎的临床病理特点及鉴别诊断。方法 分析３例肉芽肿性阿米巴脑炎的临床特点,ＣＴ所见的病理改变。结果 肉芽肿性阿米巴脑炎是一个慢性的临床过程,其临床特点是常出现头痛,轻度发热,癫痫发作,偏瘫和昏迷。腰穿脑脊液压力轻度增高,ＣＳＦ中可见淋巴细胞和中性白细胞,糖的含量低,蛋白中度增高。     

扩张性心肌病的病理形态学观察

目的:研究扩张性心肌病的病变特点,探索病变发生发展的机理。方法:利用BATISTA手术方法切取 8例扩张性心肌病患者左室心肌,进行大体、光镜及超微结构的形态学观察。结果:扩张性心肌病从大体上可分为室壁增厚及脂肪浸润两种类型。室壁增厚型的病变除如常规报道外,发现心肌间微小血管内皮细胞肿胀,管腔普遍狭窄,甚至闭塞。电镜证实是因内皮细胞中有大量 10 0nm大小的均质分泌颗粒所致。与之毗邻的损伤心肌细胞内亦有完全相同的分泌颗粒。结论:从形态学推测此种分泌颗粒来源于损伤的心肌细胞,进入邻近的内皮细胞后,加重了心肌缺血,此恶性循环可能导致扩张性心肌病不断恶化进展.     

心肌致密化不全的临床病理分析

目的 探讨心肌致密化不全的临床病理特征.方法 收集5例心肌致密化不全患者的临床症状、体征、心电图及超声心动图情况,测量心脏的大体情况,包括心脏的重量、纵长、横宽及各瓣膜环的长度、心室流人道和流出道的长度、心室壁的厚度.常规制片,磷钨酸苏木精染色、弹力纤维染色,光镜观察心肌情况及冠状动脉的改变.结果 5例患者均为男性,29-57岁,临床均有胸闷症状,心电图显示心律失常,超声心动图检查3例诊断为心肌致密化不全,病理分析可见受累心腔内显示有异常粗大的肌小梁和交错深陷的隐窝,从心底到心尖致密心肌逐渐变薄;心内膜为增厚的纤维组织,内层非致密心肌肌束粗大紊乱、细胞核畸形,外层致密心肌肌束走行及形态基本正常,细胞核大小均匀.结论 心肌致密化不全具有特有的病理组织学变化,临床无特异性表现,超声心动图是临床诊断心肌致密化不全的主要辅助手段之一.     

NIDDM大鼠模型的建立及其病理学观察

非胰岛素依赖性糖尿病（NIDDM）发病率逐年升高，其慢性并发症已成为导致病人死亡的主要原因。为此，我们试验建立一种稳定的NIDDM动物模型以使对其进行深入的研究。l材料和方法1．1材料本校动物部提供新生雄性Wistar大鼠。链豚佐菌素（STZ）溶液用0．lmol．L－’，pH4．4的柠檬酸钠缓冲液配制。1．2方法雄性Wistar大鼠生后2天随机分成两组：正常对照组（l只）和NIDDM组（60只）。正常对照组腹腔注射柠檬酸钠缓冲液，NIDDM组腹腔注射STZ，按90mg·kg‘，分别于实验第10周和第25周检测糖耐量。第25周处死动物，迅速取出胰腺，盘…     

糖尿病心肌病的研究进展

1972年,Rubler等[1]在无明显冠状动脉粥样硬化的糖尿病(diabetes mellitus,DM)患者中观察到一种特异性心肌病(specific cardiomyopathy).1974年,Hambry等[2]通过进一步病理研究,首次提出了糖尿病心肌病(diabetic cardiomyopathy,DCM)的概念,并认为糖尿病心肌病与糖尿病特有的代谢有关.     

隐原性机化性肺炎的临床病理学观察

目的探讨隐原性机化性肺炎（COP）的临床病理学特点及其鉴别诊断。方法对11例经电视胸腔镜或小切口开胸肺活检诊断为COP的病例进行临床、影像和病理学比较分析,治疗后随访。结果COP主要发生于40岁以上的女性,临床主要表现为咳嗽和咳痰、活动后气促。高分辨CT表现为两肺散在斑点、斑片和条索状阴影,无蜂窝肺。COP的主要病理变化是呼吸性细支气管及以下的小气道和肺泡腔内有息肉状的肉芽组织增生,病变时相一致,呈斑片状和支气管周围分布。对糖皮质激素的反应率为81．8％（P〈0．01）。随访6～134个月不等,除1例病情呈进行性加重外,其余病例病情稳定。结论COP对糖皮质激素有较好的反应和预后,临床和影像学不典型时进行外科肺活检病理组织学检查是非常必要的,肺活检应多点取材以免误诊。     

内皮细胞微粒与糖尿病心肌病

内皮细胞激活、损伤、凋亡时,会向细胞外释放内皮微粒,其作为反映内皮细胞功能的新型标记物,在多种病理状态时都有增加。糖尿病心肌病的病理过程中,内皮损伤、血管再生、氧化应激与炎症反应以及肾素血管紧张素系统激活等过程都与内皮微粒存在紧密联系。     

致心律失常性右室心肌病心力衰竭期的病理特点分析

目的 通过分析致心律失常性右室心肌病(ARVC)心力衰竭期的病理改变,以进一步了解其临床分期与病理表型的关系.方法 从2004-2007 年在阜外心血管病医院接受心脏移植的心力衰竭病例中,收集病理诊断为ARVC的受体心脏8例,测量心脏重量,评价左右心室心腔扩张、心肌细胞肥大、脂肪浸润、纤维化、附壁血栓和伴发心肌炎等指标,注意左心室受累情况,并进行病理分型.结果 8例中的7例为经典型(即右心室改变为主),1例为左优势型(左心室改变为主),未见双室型病例.组织学均为纤维脂肪型,未见单纯脂肪型病例.经典型病例的右心室中、重度扩张,少数有室壁瘤形成,其中6例伴左心室受累,受累左心室轻、中度扩张,心肌广泛间质纤维化,部分病例伴替代性疤痕,而脂肪浸润量小,多局限于心外膜下.左心室心肌细胞肥大普遍.而左优势型的左心室重度扩张,弥漫间质纤维化和局部透壁性脂肪浸润.8例中3例左心室明显肥厚,3例查见双室附壁血栓,1例伴局灶性心肌炎.结论 ARVC心力衰竭期的左心室受累多见而严重,左心室间质纤维化突出,心肌细胞肥大明显,但脂肪替代少见和局限.左、右心室多扩张,可见附壁血栓,应注意与扩张型心肌病等鉴别.     

糖尿病心肌病动物模型的建立

背景：糖尿病性心肌病是导致糖尿病患者死亡率增加的重要因素,是一种严重的糖尿病并发症。因此为研究糖尿病心肌病的发病机制及诊疗提供有效的实验动物模型显得尤为重要。 目的：探索关于构建Wistar大鼠糖尿病心肌病动物模型的方法。 方法：将40只大鼠随机分为对照组(n=10)和糖尿病心肌病组(n=30)。糖尿病心肌病组应用链脲菌素60 mg/kg一次性腹腔注射法构建糖尿病心肌病大鼠模型;对照组大鼠给予等体积的枸橼酸缓冲液。两组大鼠均以非高脂高糖的普通饲料喂养。 结果与结论：与对照组相比,糖尿病心肌病组大鼠在腹腔注射链脲菌素3周后血糖显著升高,心肌细胞排列紊乱,细胞核大小不规则,心肌组织内胶原含量明显增多且胶原纤维粗大排列紊乱,同时反映糖尿病心肌病心肌纤维化的转化生长因子β1和Ⅰ型胶原的mRNA和蛋白表达水平亦明显增高。说明一次性腹腔注射大剂量的链脲菌素(60 mg/kg)并给予非高脂高糖的普通饲料喂养,可以构建稳定的1型糖尿病心肌病模型,方法安全有效,可行性高。 中国组织工程研究杂志出版内容重点：肾移植;肝移植;移植;心脏移植;组织移植;皮肤移植;皮瓣移植;血管移植;器官移植;组织工程     

FBXW7在糖尿病心肌病中的表达

目的:检测含F框/WD重复域蛋白7(FBXW7)在1型糖尿病大鼠心肌中的表达,探究其在糖尿病心肌病发生发展中的作用。方法:实验将大鼠分为非糖尿病组(ND组)及糖尿病4、8和12周模型组(DM组),采用链脲佐菌素(60 mg/kg)一次性腹腔注射建立1型糖尿病大鼠模型。HE染色法观察心肌病理结构变化,Western blot和免疫组化法检测心肌中FBXW7蛋白的表达变化。结果:显微镜下可见糖尿病组大鼠心肌局灶性心肌细胞变性、坏死。Western blot和免疫组化结果均显示,4周、8周及12周DM组大鼠心肌中的FBXW7表达相对于ND组显著增加(P 0. 01),但是相比于4周和8周DM组,12周DM组大鼠心肌中的FBXW7表达相对下降(P 0. 05)。结论:随着糖尿病病程的延长,FBXW7在糖尿病心肌病大鼠心肌组织中的表达呈现先升高后降低的趋势,提示其在糖尿病心肌病发生发展中发挥了一定的作用。     

MicroRNA-146在糖尿病心肌病中的调控作用

目的:探讨微小RNA-146 (miR-146)在糖尿病心肌病(DCM)发病机制中的作用,观察miR-146及其下游靶基因表达水平的变化。方法:60只雄性C57BL/6小鼠随机分为实验(DCM)组和对照(control)组,每组30只,实验组采用低剂量(50 mg/kg链脲佐菌素(STZ)腹腔注射诱导建立糖尿病心肌病模型,对照组给予等量枸橼酸钠缓冲液腹腔注射,建模12周后取心脏做HE和Masson染色观察心脏病理改变,RT-qPCR检测miR-146 a和miR-146b及其下游靶基因白细胞介素-1受体相关激酶1(IRAK1)和TNF受体相关因子6(TRAF6)的mRNA表达,Western blot检测IRAK1和TRAF6的蛋白表达。结果:12周末HE染色显示,DCM组心肌肥大,结构紊乱;Masson染色显示,DCM组心肌内胶原纤维增多;RT-qPCR检测结果显示,DCM组中miR-146a及miR-146b较control组表达明显减少(P 0. 01),IRAK1的mRNA水平明显增高(P 0. 01),而TRAF6的mRNA水平下降(P 0. 01);Western blot检测结果显示DCM组的IRAK1蛋白表达增加,TRAF6的蛋白表达降低(P 0. 01)。结论:miR-146可能通过调节IRAK1介导的炎症反应参与糖尿病心肌损伤的发生发展。     

Pathologic evidence of extensive left ventricular involvement in arrhythmogenic right ventricular cardiomyopathy.

Arrhythmogenic right ventricular cardiomyopathy (also known as arrhythmogenic right ventricular dysplasia) is characterized by adipose or fibroadipose tissue replacement of the right ventricular myocardium, whereas the left ventricle is substantively spared. Two cases of the disease with evidence of extensive left ventricular involvement at pathologic examination are described. Hearts from two patients who died suddenly showed full-thickness right ventricular fatty infiltration associated with extensive left ventricular involvement (greater than 50% of myocardial thickness). These findings might explain the reported clinical features of left ventricle dysfunction in a subset of patients with arrhythmogenic right ventricular cardiomyopathy. In view of the biventricular involvement of the disease, it should simply be termed "arrhythmogenic cardiomyopathy."     

Defective sarcoplasmic reticular calcium transport in diabetic cardiomyopathy

The effects of insulin and thyroid hormone treatments on cardiac sarcoplasmic reticular function were investigated in chronic streptozotocin-induced diabetes in rats. ATP-dependent Ca2+ transport and Ca2+-stimulated ATPase activities were depressed significantly in microsomal samples from diabetic rats in comparison with control (P less than 0.05). This defect was seen at various times of incubation (1-20 min) and different concentrations of free Ca2+ (10(-7) to 10(-5) M Ca2+) and was accompanied by changes in the protein composition and phospholipid contents of the microsomal fraction. The defect in calcium transport in microsomal vesicles was not evident until 28 days after streptozotocin (65 mg/kg iv) injection, whereas increases in plasma glucose levels due to insulin-deficiency occurred within 3 days. All changes in function and composition of the sarcoplasmic reticulum were reversed by insulin administration to the diabetic rats. Although the plasma level of thyroid hormone was decreased in the diabetic rat, thyroid hormone treatment did not restore microsomal calcium transport in the diabetic animals. The results of this study provide some evidence that the depression in cardiac sarcoplasmic reticular calcium accumulation during diabetes is a consequence of insulin deficiency and associated chronic metabolic changes but the hypothyroid condition that accompanies experimental diabetes does not appear to play any role in this defect.     

Apocynin降低1型糖尿病小鼠心肌组织炎症因子的表达

目的： 探讨NADPH氧化酶抑制剂apocynin对1型糖尿病小鼠心肌组织IL-1β、IL-18、TNF-α和COX-2表达的影响及其机制研究。方法: C57小鼠腹腔注射STZ建立1型糖尿病动物模型,44只8周龄雄性小鼠分为对照组（sham,n=6）、apocynin对照组（Apo,n=6）、1型糖尿病组（STZ,n=16）及1型糖尿病apocynin治疗组(STZ+Apo,n=16)。实验于8周末结束,运用超声心动图检测小鼠心脏功能,以实时定量RT-PCR技术测定心肌组织IL-1β、IL-18、TNF-α和COX-2 mRNA表达,以Western blotting检测心肌组织磷酸化Akt表达。结果: 1型糖尿病小鼠心脏功能降低伴随心肌组织IL-1β、IL-18、TNF-α和COX-2 mRNA表达增加,STZ+Apo组小鼠心脏功能增高伴随心肌组织IL-1β、IL-18、TNF-α和COX-2 mRNA表达减少;1型糖尿病小鼠心肌组织磷酸化Akt显著减少,STZ+Apo组心肌组织磷酸化Akt明显增加。结论: Apocynin提高1型糖尿病小鼠心脏功能伴随显著减少心肌组织IL-1β、IL-18、TNF-α和COX-2 mRNA的表达,其机制可能与增加心肌组织磷酸化Akt表达密切相关。     

Emerging role of epigenetics and miRNA in diabetic cardiomyopathy

The prevalence of heart failure independent of coronary artery disease and hypertension is increasing rapidly in diabetic patients. Thus, this pathophysiology has been recognized as a distinct clinical entity termed “diabetic cardiomyopathy.” Several studies support the notion that diabetes is a threatening insult for the myocardium resulting in functional, cellular, and structural changes manifesting as a cardiac myopathy. Recent data suggested that epigenetics including DNA and histone modifications as well as microRNAs play an important role in the development of cardiac diseases. The role of epigenetics in diabetes is largely recognized; however, its role in diabetes-associated cardiomyopathy remains elusive. Thus, molecular, cellular, and functional modulations in the diabetic cardiomyopathy will be investigated in this review. Moreover, particular attention will be drawn on the epigenetic mechanisms that may play an important role in the pathophysiology of diabetic cardiomyopathy.     

Autophagy in the diabetic heart: A potential pharmacotherapeutic target in diabetic cardiomyopathy

Association of diabetes with an elevated risk of cardiac failure has been clinically evident. Diabetes potentiates diastolic and systolic cardiac failure following the myocardial infarction that produces the cardiac muscle-specific microvascular complication, clinically termed as diabetic cardiomyopathy. Elevated susceptibility of diabetic cardiomyopathy is primarily caused by the generation of free radicals in the hyperglycemic milieu, compromising the myocardial contractility and normal cardiac functions with increasing redox insult, impaired mitochondria, damaged organelles, apoptosis, and cardiomyocytes fibrosis. Autophagy is essentially involved in the recycling/clearing the damaged organelles, cytoplasmic contents, and aggregates, which are frequently produced in cardiomyocytes. Although autophagy plays a vital role in maintaining the cellular homeostasis in diligent cardiac tissues, this process is frequently impaired in the diabetic heart. Given its clinical significance, accumulating evidence largely showed the functional aspects of autophagy in diabetic cardiomyopathy, elucidating its intricate protective and pathogenic outcomes. However, etiology and molecular readouts of these contrary autophagy activities in diabetic cardiomyopathy are not yet comprehensively assessed and translated. In this review, we attempted to assess the role of autophagy and its adaptations in the diabetic heart. To delineate the molecular consequences of these events, we provided detailed insights into the autophagy regulation pieces of machinery including the mTOR/AMPK, TFEB/ZNSCAN3, FOXOs, SIRTs, PINK1/Parkin, Nrf2, miRNAs, and others in the diabetic cardiomyopathy. Given the clinical significance of autophagy in the diabetic heart, we further discussed the potential pharmacotherapeutic strategies towards targeting autophagy. Taken together, the present report meticulously assessed autophagy, its adaptations, and molecular regulations in diabetic cardiomyopathy and reviewed the current autophagy-targeting strategies.