扩张型心肌病心脏移植受者心脏病理学观察及微血管内皮细胞的表达及分布

目的:观察扩张型心肌病(DCM)心脏移植受者心脏病理学特点及微血管内皮细胞的表达及分布,初步探讨内皮细胞与心肌纤维化的作用。方法:以2012年1月至2017年6月期间,本院收治的10例因DCM终末期行心脏移植患者的受者心脏作为研究对象。对照组采用来自法医鉴定中心的非疾病死亡的正常成年人尸检心脏标本6例。采用HE染色、Masson三色组织化学染色观察DCM病理学改变,采用免疫组织化学方法检测CD34和α-SMA,观察微血管内皮细胞在DCM患者心肌组织中的表达。结果:(1)光镜下,终末期DCM的主要病理改变是心肌细胞退行性变,心肌间质纤维化;(2)通过透射电镜观察发现终,末期DCM主要改变是心肌退行性变,心肌肌原纤维Z线排列不规则,部分心肌细胞核肥大,心肌肌原纤维灶性溶解,心肌间质水肿,线粒体增多,线粒体肿胀空泡化,可见髓鞘样结构,心肌间质毛细血管内皮细胞胞质肿胀,细胞连接消失,吞饮小泡减少;(3)两组心肌组织中均有微血管内皮细胞分布,DCM中CD34表达明显低于对照组,α-SMA的表达明显高于对照组。结论:DCM中血管内皮细胞的超微结构变化,可能导致其功能改变,内皮细胞可能通过内皮间质细胞转化参与了DCM中心肌纤维化。     

68例大心脏移植的受体心脏病理学特征分析

目的:分析原发性扩张型心肌病、冠心病、高血压性心脏病及糖尿病心肌病的终末期临床与病理学特点,探讨病理形态学对上述疾病鉴别诊断的价值。方法:以2007年6月至2016年6月期间,本院收治的68例终末期有扩张表现的心脏移植心肌疾病患者为研究对象,将他们分为四组:扩张型心肌病组;冠状动脉粥样硬化性心脏病组;高血压性心脏病组;糖尿病心肌病组。对其临床资料进行回顾性分析;观察移植受体心脏的大体病理改变,并采用H&E染色,Masson、PTAH、天狼猩红等组织化学染色,SMA、Desmin、CD31、CD34等免疫组织化学染色,对移植受体心脏左心室心肌组织进行组织病理学观察。结果:(1)缺血性心肌病组及糖尿病心肌病组的发病年龄明显高于扩张型心肌病组,P=0.0003及P=0.02。与扩张型心肌病组相比,高血压心脏病组的室间隔厚度(1.59±0.09)cm及心脏重量(582.7±38.29)g明显高于扩张型心肌病组(室间隔平均厚度(1.30±0.07)cm;心脏重量(430.7±26.06)g,P=0.03及P=0.0003。(2)四组显微镜下观察发现:扩张型心肌病的主要病理改变是心肌细胞呈退行性变,主要表现心肌细胞颗粒状变性,可见肌丝断裂、溶解消失,心肌间质水肿,心肌间质反应性纤维化。缺血性心肌病的主要病理改变是:可见心肌梗死、坏死周围出现肉芽组织及纤维瘢痕灶及替代性心肌纤维化,间质常可见淋巴、浆细胞浸润。高血压心脏病的主要病理改变是:心肌纤维排列规则,部分心肌细胞肥大,核大、畸形;心肌间质纤维化明显;心肌内,尤其是室间隔心肌组织内常见小冠状动脉管壁增厚。糖尿病心肌病的主要病理改变是:心肌细胞可出现散在性微小坏死灶,心肌间质和血管周围明显纤维化,可见心肌间小冠状动脉管壁增厚,基底膜增厚。(3)天狼猩红染色观察发现终末期心脏病心肌纤维化中胶原纤维主要为Ⅰ型及Ⅲ型胶原纤维,并且Ⅰ型胶原纤维的数量多于Ⅲ型。(4)免疫组化结果发现SMA染色阳性、Desmin染色阴性的肌纤维母细胞数目增多。结论:(1)病理形态学在扩张型心肌病与缺血性心肌病、高血压心脏病及糖尿病心肌病鉴别诊断中有一定意义。(2)心脏扩大前1~5年有高血压病史,出现明显室间隔肥厚,心肌间质明显纤维化及心肌间质小血管壁增厚常常提示诊断高血压心脏病。(3)心肌内微小血管壁增厚及基底膜增厚、血管周心肌纤维化是糖尿病心肌病主要的病理形态学特点,对糖尿病心肌病的诊断有重要意义。(4)肌纤维母细增生可能是终末期心脏病心肌纤维化发生中一种关键的病理因素。     

糖尿病心肌病中线粒体形态及动力学的研究进展

糖尿病心肌病(DCM)的特征包括左室功能降低、独立出现冠心病与动脉粥样硬化。DCM时钙调节紊乱、代谢改变和氧化应激,表现为线粒体能量的异常改变。DCM时心肌组织常伴随线粒体形态学的改变,提示其病理过程涉及线粒体动力学变化。虽然心肌纤维限制了线粒体形态学的改变,但有研究表明,DCM心肌组织确实存在线粒体形态学的改变。DCM心肌线粒体形态改变与线粒体功能紊乱独立相关,但在导致DCM的进程中,线粒体形态学变化与功能改变的具体关系尚不清楚。调节线粒体动力学将成为干预DCM的新靶点。     

T—2毒素和低硒饲料对雏鸡心肌细胞损伤的电镜观察

低硒饲料每天加入０．２－０．４ｍｇ／ｋｇＴ－２毒素连续喂养雏鸡９周，动物体重增长明显减慢。光镜下未见明显的凡肌组织病理学改变。电镜下观察到低硒饲料组的主要改变是心肌细胞少数区域的线粒体轻度肿胀；有的线粒体嵴断裂，局部空化可见髓梓小体结构。肌浆网扩张，内壁有电子密度较高的物质沉积。Ｔ－２毒素组还可见肌原纤维间不同密度的空泡改变，有的集聚在一起，邻近的肌纤维受压位移低硒饲料加Ｔ－２毒素组的亚细胞形态具     

肥厚性心肌病分型及其临床表现

肥厚性心肌病(HCM)有特殊的心肌细胞结构改变,肌纤维增粗,排列紊乱;室间隔病变最明显,双侧心室均可累及,以左室为多;超声心动图有特征性改变。本文就HCM累及的部位、范围进行分型,结合临床表现进行分析。材科和方法选择经二维超声心动图,已排除其他原因引起的心肌肥厚而确诊为HCM者65例。年龄     

重视肥厚型心肌病的多重心电图表现

肥厚型心肌病(HCM)是一种由心肌肌小节基因突变所致的、以心肌肥厚、心肌纤维排列紊乱为特征的原发性心肌疾病,国外报道每500人中即有1例患者。     

肥厚型心肌病的心电图特征——重视肥厚型心肌病的多重心电图表现

肥厚型心肌病（HCM）是一种由心肌肌小节基因突变所致的、以心肌肥厚、心肌纤维排列紊乱为特征的原发性心肌疾病，国外报道每500人中即有1例患者。     

糖尿病心肌病中自噬与凋亡的相互作用

糖尿病心肌病(diabetic cardiomyopathy,DCM)是糖尿病主要的心血管并发症之一.氧化应激、线粒体功能紊乱、炎症反应、心肌纤维化、细胞凋亡和自噬均参与DCM的发生发展.越来越多的证据表明,心肌细胞凋亡与自噬水平的改变贯穿于DCM的发生发展过程,且二者之间的联系可能在DCM的发病机制中发挥重要作用.目...     

心肌细胞骨架蛋白在终末期扩张型心肌病患者中的表达

目的:探讨扩张型心肌病(DCM)及其他终末期心脏病患者衰竭心肌的细胞骨架蛋白actin、desmin、sarcoglycans(SGs)的表达情况。方法:9例终末期DCM(DCM组)与6例其他终末期心脏病患者和1例非心源性脑死亡者(对照组)的心肌标本进行免疫组化检测。结果:免疫组化检查结果显示,DCM组中8例存在上述多个骨架蛋白表达异常,且均有至少1个SGs亚型异常,其中5例伴有actin和(或)desmin的表达异常,心功能Ⅲ~Ⅳ级者骨架蛋白的异常(>2个)较心功能Ⅱ~Ⅲ级者(≤2个)多;对照组中4例心功能Ⅳ级者也有细胞骨架蛋白表达异常,包括α、δ-SG异常各1例(分别为心脏肉瘤,缺血性心肌病),actin异常1例(先天性心脏病),以及α、β-SG及actin均异常1例(呈DCM表现的终末期非梗阻性肥厚型心肌病);1例脑死亡者心肌中未检出上述骨架蛋白表达异常。结论:DCM衰竭心肌中存有多种细胞骨架蛋白的表达异常,多数为actin、desmin、SGs表达水平的降低,提示由细胞骨架蛋白的表达异常所致的细胞内外力的传递缺陷可能是导致终末期心脏病的共同发病或演进机制。     

缓慢心律失常患者心内膜心肌活检的临床病理及超微结构研究

目的通过对植入起搏器的缓慢心律失常患者右心室心肌的临床病理研究及超微结构分析，探讨缓慢心律失常病因、判断病理改变程度及超微结构特点。方法对13例需植入起搏器的缓慢心律失常患者在植入术中行心内膜心肌活检。三度房室阻滞5例，病态窦房结综合征8例。标本分别进行光镜及电镜检查。以5例高血压病Ⅰ期患者为对照。采用SekiguchiM的组织病理学半定量分析方法，按照病变严重程度进行4级病理计分。结果病理诊断心肌病1例、非特异性改变12例。光镜结果缓慢心律失常患者均有不同程度心肌细胞肥大、心肌变性及间质纤维化，比较病态窦房结综合征组和三度房室阻滞组患者改变差异无显著性(P＞0.05)。组织病理学衰竭指数平均值(2.2±1.2)。电镜结果病态窦房结综合征组和三度房室阻滞组比较，病态窦房结综合征组线粒体数目增加、肌浆网扩张、脂褐质沉着增加及空泡变性差异均有显著性(P＜0.05)。与对照组比较缓慢心律失常患者线粒体数目增加、线粒体形态改变、空泡变性及肌原纤维断裂疏松化差异均有显著性(P＜0.05)。结论心内膜心肌活检对于了解缓慢心律失常发病原因缺乏特异性，对判断病理改变程度及超微结构有一定价值。缓慢心律失常者心肌均有不同程度病理改变，光镜改变轻，超微结构改变则较明显。     

Myocardial dna strand breaks are detected in biopsy tissues from patients with dilated cardiomyopathy

Background: Progressive damage of cardiomyocytes with interstitial and replacement fibrosis accompanied by less inflammatory cell infiltration is observed in patients with dilated cardiomyopathy (DCM), suggesting some other mechanisms rather than necrotic cell death. Hypothesis: The aim of this study was to assess the possible involvement of apoptotic process in the pathogenesis of DCM and myocarditis. Methods: Endomyocardial biopsy was performed in patients with DCM (n = 9). myocarditis (n = 4), or atypical chest pain syndrome (as controls; n = 5). The TUNEL method was used for in situ detection of oligonucleosomal DNA strand breaks. Results: The TUNEL-positive cells were observed in three of nine patients with DCM and in all four with myocarditis, but in none of the controls. The TUNEL-positive nuclei were observed exclusively in cardiomyocytes in DCM, whereas in myocarditis they were detected mainly in interstitial cells and in a few myocytes. In DCM, interstitial fibrosis was greater in the TUNEL-positive than in TUNEL-negative patients (p<0.05). In either DCM or myocarditis, electron microscopic examination could not reveal morphologic features of apoptosis of cardiomyocytes. Conclusion: The DNA strand breaks were detected in cardiomyocytes in patients with DCM and mainly in interstitial cells in myocarditis. It is possible that the DNA strand breaks can be involved in mechanisms of progressive loss of functional cardiac units in these myocardial diseases.     

Serum markers of angiogenesis and myocardial ultrasonic tissue characterization in patients with dilated cardiomyopathy

BACKGROUND AND AIMS: It has been proven that a disturbance in angiogenesis contributes to the progression of myocardial interstitial fibrosis in idiopathic dilated cardiomyopathy (DCM). This study was designed to evaluate the relationship between serum activity of angiogenic factors and myocardial ultrasonic tissue characterization in patients with DCM. METHODS AND RESULTS: We studied 30 patients with DCM and 15 healthy control subjects. Serum levels of vascular endothelial growth factor (VEGF), interleukin (IL)-4 and IL-13 were measured using enzyme-linked immunosorbent assay. We determined calibrated myocardial integrated backscatter (IB) as the value of myocardial interstitial fibrosis using ultrasonic tissue characterization and also quantified the magnitude of cyclic variations in IB (CV-IB). Serum levels of VEGF and IL-13 were significantly higher in patients with DCM than in control subjects (both P<0.05). Calibrated IB was significantly higher and CV-IB was markedly lower in patients with DCM than in control subjects (both P<0.01). In patients with DCM, the levels of IL-13 significantly correlated with calibrated IB (r=0.520, P=0.018). In addition, there was a significant negative correlation between levels of VEGF and CV-IB (r=-0.611, P=0.007). CONCLUSION: The increase in serum VEGF and IL-13 may be closely related to alterations in myocardial texture in DCM.     

Immunohistological evidence for a chronic intramyocardial inflammatory process in dilated cardiomyopathy.

OBJECTIVE: To determine whether immunohistochemical analysis of cardiac biopsies from patients presenting clinically as dilated cardiomyopathy (DCM) show a chronic inflammatory process. DESIGN: Comparative case control study. SETTING: Tertiary referral centre. PATIENTS: Biopsies from 170 patients with DCM and 85 control patients with other cardiac diseases. RESULTS: Nine patients had sufficient interstitial inflammatory cells to be called borderline myocarditis on conventional histology, leaving 161 patients with DCM. In 78 patients with DCM (48%) there were T lymphocytes in the myocardium. In 48 (62%) of these 78 T lymphocyte densities were in the range 2-14 per high power field (HPF), equivalent to 7-50 per mm2 of tissue. In 43 (89%) interstitial and endothelial immune activation was demonstrated by MHC expression. In 30 patients with T cell counts in the range 1.5-2.0 per HPF, 80% also showed endothelial activation. Lymphocyte density correlated with increased expression of MHC class I and II antigens and the adhesion molecules ICAM, VCAM, ELAM, LFA-3, and GMP140. In all control biopsies the T lymphocyte density was less than 1.0 per HPF (less than 2-5 per mm2 of tissue). CONCLUSIONS: Nearly half the patients with DCM had increased T lymphocyte density and immune activation of endothelial and interstitial cells in their cardiac biopsies. A chronic autoimmune process is still active within the myocardium in a significant percentage of patients with DCM. Immunohistochemical analysis of cardiac biopsies will enhance the sensitivity of cardiac biopsy and is essential for the diagnosis of myocarditis.     

抗人心肌线粒体抗体在病毒性心肌炎和扩张型心肌病中的检测及其意义

目的检测病毒性心肌炎(VMC)和扩张型心肌病(DCM)患者血清中是否有抗人心肌线粒体抗体存在及其意义。 方法以人心肌线粒体作抗原,应用免疫点印迹在29例VMC(VMC组)、24例DCM(DCM组)、33例其它心脏病(OCD组)及20例健康献血者(HBD组)进行抗人心肌线粒体抗体检测,用免疫印迹方法检测其抗原分子量。 结果VMC组(12例,41.4%)DCM组(10例,41.7%)抗人心肌线粒体抗体阳性明显高于OCD组(2例,6.1%)及HBD(0%);②抗体阳性的VMC和DCM患者中有43.8%的心肌肌钙蛋白T升高,抗体阴性者为12.0%(P＜0.05)有显著性差异;③人心肌线粒体特异性抗原的分子量为30KD。 结论①在VMC和DCM患者血清中存在抗人心肌线粒体抗体,说明部分VMC及DCM与自身免疫有关,该抗体是引起心肌损伤的因素之一,对该抗体的检测可作为VMC和DCM的辅助诊断手段之一;②该抗体的特异性抗原可能为人心肌线粒体腺苷酸转位酶。     

促红细胞生成素衍生肽抑制小鼠糖尿病心肌病损伤的作用研究

目的 探讨促红细胞生成素衍生肽又称螺旋B表面肽（helix B surface peptide,HBSP）在糖尿病小鼠心肌病中的保护作用及其可能机制。 方法 80只（20~25）g雄性昆明小鼠随机分为对照组（n=20）、对照+HBSP组（n=20）、糖尿病心肌病（DCM）组（n=20）、DCM+HBSP组（n=20）。链脲佐菌素（STZ）对小鼠腹腔注射诱导1型糖尿病,最后1次STZ注射完成后第5日,血糖仪检测小鼠尾静脉血葡萄糖水平,3次测量随机血糖均≥16.7 mmol/L的视为糖尿病小鼠。糖尿病小鼠继续喂养12周,小动物超声检测提示心功能减退的为DCM小鼠。从中随机选出20只,腹腔注射HBSP 30 μg/（kg·d）,连续4周,为DCM+HBSP组。采用小动物超声分别检测各组小鼠心功能,TUNEL法检测各组小鼠心肌组织细胞凋亡率,天狼星红染色观察各组小鼠的心肌纤维化程度,Western blot检测心肌组织Akt、p-Akt、GSK3β和p-GSK3β的表达。 结果 与DCM组相比,DCM+HBSP组左室射血分数〔LVEF（%）〕及左室短轴缩短率〔［LVFS（%）〕增加（P<0.05）,左心室收缩末期容积（LVESV）和左心室舒张末期容积（LVEDV）降低（P<0.05）、心肌组织细胞凋亡率降低（P<0.05）、心肌纤维化程度减少（P<0.01）、p-Akt表达增加（P<0.05）,p-GSK3β的表达增加（P<0.01）。 结论 HBSP能够抑制小鼠DCM心肌细胞凋亡、减轻心肌间质纤维化、改善心功能,Akt-GSK3β通路的激活可能参与了HBSP减轻小鼠DCM损伤的保护作用。     

合用开博通和螺内脂对扩张型心肌病心肌纤维化及心功能的影响

目的评价血管紧张素转换酶抑制剂开博通及醛固酮拮抗剂螺内脂逆转原发性扩张型心肌病(DCM)心肌纤维化及改善心功能的作用。方法放射免疫法测定45例原发性DCM患者应用开博通及螺内脂治疗前及治疗6个月后血清心肌纤维化指标:血清Ⅲ型前胶原(PCⅢ)、层粘连蛋白(LN)、透明质酸(HA);超声测定左心室内径、左心房内径、右心室内径及左心室射血分数(LVEF)。结果应用开博通及螺内脂治疗后血清心肌纤维化指标显著下降:PCⅢ(243.4±50.3 vs 186.6±38.4P<0.01)、LN(224.7±50.1 vs 160.8±36.8P<0.01)、HA(259.4±70.4 vs 173.4±40.6P<0.01);心功能明显改善:左心室内径(62.4±11.4 vs 51.6±10.2P<0.05)、左心房内径(48.6±10.3 vs 40.7±8.9P<0.05)、右心室内径(30.4±7.3 vs 23.4±5.7P<0.05)、LVEF(36.5±9.6 vs 41.8±11.8P<0.05)。结论开博通及螺内脂能明显逆转原发性DCM心肌纤维化,改善其心功能。     

A trial diagnosis of latent dilated cardiomyopathy

To diagnose latent dilated cardiomyopathy (latent DCM), we performed loading echocardiography with Angiotensin II and ergometer exercise in 41 patients. Twenty-one patients were suspected of having latent DCM because of histories, of heart failure of myocarditis; 10 patients had DCM; and 10 normal persons served as controls. On angiotensin II loading, cardiac function deteriorated in the DCM group, but it was maintained in the normal controls. Nine patients in the latent DCM group showed the same pattern as normals (L1-group), and 12 did as the DCM group (L2-group). Although % fractional shortening, end-diastolic and end-systolic dimensions of the left ventricle did not differ between the L1 and L2-groups, the A/R, the ratio of the pulsed Doppler echocardiogram at the left ventricular inflow tract, was larger and the exercise change of the % fractional shortening and exercise tolerance were less in the L2-group than in the L1-group. Furthermore, the biopsy findings of the L2-group were similar to those of the DCM group in terms of myocardial degeneration, myocardial hypertrophy and interstitial fibrosis. Thus, patients in the L2-group were thought to have a risk for DCM, and were cases of latent DCM. Angiotensin II loading is thought to be useful for diagnosing such cases.     

糖/血小板反应素-1/转化生长因子β1信号传导途径在糖尿病心肌病发病中的作用

目的探讨糖／血小板反应素-1（TSP-1）／转化生长因子（TGF）B。信号传导途径在糖尿病心肌病发病中的作用。方法采用高脂高热量饮食诱导出胰岛素抵抗,加小剂量链脲佐菌素注射建立糖尿病心肌病动物模型,以Masson染色、实时定量逆转录-聚合酶链反应、Western blot技术,检测左室心肌胶原含量、TSP-1、TGFβ1 mRNA和蛋白质表达水平的变化。结果与对照组相比,糖尿病心肌病大鼠左室心肌组织胶原含量明显高,存在心肌间质纤维化;TSP-1 mRNA和蛋白质表达均明显高,TGFβ1 mRNA、活性和非活性TGFβ1蛋白质表达亦明显高;TSP-1、TGFβ1 mRNA水平与空腹血糖、心肌组织胶原含量以及左室舒张功能指标均明显相关,TSP-1、活性TGFβ1蛋白质表达水平与空腹血糖、心肌组织胶原含量以及左室舒张功能指标之间亦存在明显的相关关系,但非活性TGFβ1蛋白质表达水平与空腹血糖、心肌组织胶原含量以及左室舒张功能指标之间无相关性。结论糖／TSP-1／TGFβ1信号传导途径在糖尿病心肌病时心肌间质纤维化发生发展过程中可能起着重要的作用,为临床上糖尿病心肌病的治疗提供了新的靶点。     

晚期扩张型心肌病患者心肌Cx43蛋白表达的研究

目的:探讨晚期扩张型心肌病(DCM)患者心肌连接蛋白43(Cx43)表达变化及其意义。方法:运用免疫组化和图像分析技术,对5例晚期DCM患者和4例因其他心脏疾病(A对照组)行心脏移植手术切除的心脏及4例机械性损伤死者(B对照组)的左心室心肌Cx43蛋白表达进行定位和定量研究。结果:DCM患者心肌Cx43蛋白表达较清晰,主要位于心肌闰盘处,呈条状、斑点或颗粒状散在分布,有的散在分布于心肌细胞侧边;A对照组表达清楚,位于心肌闰盘处,主要呈条状,少数呈斑点状散在分布,而心肌侧边分布很少;B对照组阳性着色较淡,在闰盘处呈条状分布,少有斑点状散在分布,心肌侧边几无表达。定量检测和统计分析发现,DCM组心肌Cx43蛋白表达的量低于A对照组但高于B对照组。心肌Cx43蛋白表达的平均光密度,DCM组与A对照组、B对照组相比,A对照组与B对照组相比,差异均有统计学意义(P<0.01);心肌Cx43蛋白表达的S值,DCM组、A对照组、B对照组间比较,差异均无统计学意义(P>0.05)。结论:晚期DCM患者心肌Cx43蛋白表达的数量和分布均发生改变,这种变化很可能是导致DCM患者发生心律失常和心功能衰竭的病理基础。     

Immunadsorption als Therapieverfahren der dilatativen Kardiomyopathie

Abnormalities of the cellular and humoral immune system have been described in patients with dilated cardiomyopathy (DCM). For patients with DCM, immunochemical analyses of myocardial biopsies have demonstrated myocardial inflammation. Various circulating cardiac antibodies have been detected among DCM patients. Circulating antibodies are extractable by immunoadsorption. Recent open controlled pilot studies showed that removal of antibodies by immunoadsorption induces improvement of cardiac function in DCM. Furthermore, it decreases myocardial inflammation. This may offer a new therapeutic option for patients with severe heart failure due to dilated cardiomyopathy.