A therapeutic anti-CD4 monoclonal antibody inhibits T cell receptor signal transduction in mouse autoimmune cardiomyopathy

Background T cell immune abnormalities in patients with dilated cardiomyopathy (DCM) has been intensively studied over the past 10 years. Our previous study has suggested that immunization of mice with the peptides derived from human adenine nucleotide translocator (ANT) result in the production of autoantibodies against the ANT and histopathological changes similar to those in human DCM. The ANT peptides can induce autoimmune cardiomyopathy like DCM in Balb/c mice. In this study we aimed to focus on the molecular mechanism of T cells in the autoimmune cardiomyopathy mouse model by detecting the expression of the two T cell signaling molecules.Methods The ANT peptides were used to cause autoimmune cardiomyopathy in Balb/c mice. Anti-L3T4 or rat anti-mouse IgG was administered to the mice (n=6 in each group) simultaneously immunized with ANT. ELISA analysis was used to detect autoantibodies against the ANT peptides and the percentages of interferon-γ and interleukin-4 producing cells among splenic CD4(+) lymphocytes was determined by using flow cytometry analysis. The expression of CD45 in spleen T cells was determined by immunohistochemistry and the mRNAs of T cell signaling molecules were detected by real-time PCR.Results Treatment of ANT immunized Balb/c mice with anti-CD4 mAb caused a reduction in the gene expression of P56lck and Zap-70 and a lower level of CD45 expression by spleen T cells. Also, a reverse of the Th1/Th2 ratio that results in the reduced production of antibodies against ANT was found in the anti-CD4 monoclonal antibodies (mAb) group. Whereas irrelevant antibody (rat anti-mouse IgG) did not suppress T cell signaling molecules nor inhibit CD45 expression, and control-antibody mice did not show any significant differences compared with the DCM group.Conclusion The results show that anti-CD4 mAb is a powerful inhibitor of the early initiating events of T cell receptor (TCR) signal transduction in mouse autoimmune dilated cardiomyopathy.     

甲亢性心肌病兔心肌血管紧张素转换酶和细胞外信号调节激酶的变化

目的 探讨甲亢性心肌病的发病机制.方法 健康成年新西兰大白兔40只,按随机数字表法分为4组:空白对照组、左旋甲状腺素(L-Thy)组、咪哒普利组、缬沙坦组.L-Thy(45 μg·kg-1·d-1×28 d)腹腔注射建立甲亢性心肌病模型,第28天收集心肌标本测定左右心室心肌肥厚指数,光镜下观察心肌细胞结构,测定心肌细胞直径,Masson's染色测定胶原容积分数(collagen volumefraction,CVF),透射电镜观察心肌细胞超微结构改变,Western blot检测血管紧张素转换酶(angiotensin converting enzyme,ACE)、细胞外信号调节激酶(ERK)及磷酸化细胞外信号调节激酶(p-ERK)的蛋白表达.结果 L-Thy可诱导心肌肥厚、心肌细胞结构改变以及纤维组织增生,ACE、ERK和p-ERK蛋白表达上调,ERK及p-ERK表达与心肌细胞平均直径和CVF呈正相关.咪哒普利和缬沙坦均可显著抑制L-Thy诱导的心肌细胞肥厚和纤维化,从而降低ERK、p-ERK的表达.结论 肾素-血管紧张素系统(RAS)和ERK信号传导通路可能参与甲亢性心肌病的发病机制,ERK信号传导通路的激活可能与RAS有关,咪哒普利和缬沙坦可以抑制ERK信号传导通路的激活并改善L-Thy诱导的心肌重构.     

稳心颗粒联合尼可地尔治疗缺血性心肌病合并房性心律失常患者的效果

目的:观察稳心颗粒联合尼可地尔治疗缺血性心肌病合并房性心律失常患者的效果。方法:选取103例缺血性心肌病合并房性心律失常患者作为研究对象,以电脑随机数字表法将其分为研究组51例和对照组52例。两组均开展常规基础治疗,在此基础上,对照组采用尼可地尔治疗,研究组在对照组基础上联合稳心颗粒治疗,比较两组治疗前后心功能指标[左室舒张末期内径(LVEDD)、左室收缩末期内径(LVESD)、左室射血分数(LVEF)]水平、P波最大时限、P波离散度、6 min步行试验(6MWT)距离和不良反应发生率。结果:治疗后,研究组LVEDD和LVESD水平均低于对照组,LVEF水平高于对照组,6MWT距离长于对照组,差异有统计学意义(P<0.05);治疗后,研究组P波最大时限和P波离散度均小于对照组,差异有统计学意义(P<0.05);两组不良反应发生率比较,差异无统计学意义(P>0.05)。结论:稳心颗粒联合尼可地尔治疗缺血性心肌病合并房性心律失常患者可改善心功能指标水平,延长6MWT距离,减小P波最大时限和P波离散度,效果优于单纯尼可地尔治疗。     

心脏磁共振电影成像纹理特征与传统心功能参数分析肥厚型心肌病心衰程度的对比研究

目的：探讨心脏磁共振（cardiac magnetic resonance,CMR）电影序列纹理特征分析肥厚型心肌病（hypertrophic cardiomyopathy,HCM）患者心衰程度的可行性。方法：回顾性分析陆军军医大学第一附属医院2013年至2016年接受CMR检查的HCM患者82例,按照纽约心脏协会（New York Heart Association,NYHA）心功能分级法分组,NYHAⅠ～Ⅱ为轻度心衰组,NYHAⅢ～Ⅳ为重度心衰组。电影序列图像用MATLAB软件手动提取所有患者左室舒张末期心肌区域2次,Bland-Altman检验计算2次特征一致性,卷积神经网络（convolutional neural networks,CNN）计算优化后特征曲线下面积（area under the curve,AUC）。卡方检验比较2组患者男女分布差异性,心血管后处理软件（Circle Cardiovascular Imaging,CVI,Canada）计算左心室延时强化（late gadolinium enhancement,LGE）百分比,Argus软件计算左心室射血分数（e...     

Clinical and familial study of arrhythmogenic right ventricular cardiomyopathy

Objective　To explore the characteristics of arrhythmogenic right ventricular cardiomyopathy (ARVC). Methods　Seven patients with arrhythmogenic right ventricular cardiomyopathy and 34 members of three families were studied. All patients and family members underwent history collection, clinical examination, electrocardiogram (ECG), two-dimensional echocardiography (2-DE) and a signal averaging electrocardiogram. Programmed ventricular stimulation was performed in five patients. Results　All patients and family members had normal morphologic characteristics and normal function of the left ventricular by 2-DE. Fourteen persons had abnormal findings indicating ARVC. Five had enlargement of the right ventricular with diffused hypocontractility, eight had thin and systolic bulging in the focal anterior wall with hypokinesia and one had bulging of the inferior wall. Twenty-five persons (seven patients and 18 family members) had abnormal findings in ECG. Positive ventricular late potential was recorded in 13 persons (six patients). Two to three monomorphic ventricular tachycardia (VT) with left bundle branch block (LBBB) configurations were induced in five patients. Ventricular fibrillation was induced in two patients during the electrophysiologic study (EPS). Five patients had very high pacing threshold and/or ineffective pacing in one or many regions of the right ventricle. Two members of one family died suddenly. One member was a dwarf with ARVC. Spontaneous VT with a left bundle branch block (LBBB) configuration was recorded in five patients, polymorphic VT with extremely short coupling interval in one, and premature ventricular complexes with LBBB configuration in 12 (six patients). Conclusion　Our familial study strongly suggests that ARVC may be a hereditary disease and it is helpful in the diagnosis and detection of ARVC. The most common manifestations were abnormal structure and function of the right ventricle and abnormal ECG of repolarization and ventricular arrhythmia which originates from the right ventricle.     

Viral myocarditis and dilated cardiomyopathy: mechanisms, manifestations, and management

Viral infection of the heart is relatively common and usually of little consequence. It can, however, lead to substantial cardiac damage and severe acute heart failure. It can also evolve into the progressive syndrome of chronic heart failure. Recent studies have gone some way towards unravelling the complex mechanisms underlying the heart muscle damage that occurs after viral infection. These studies have lent support to both immune and viral mediated (independent of an immune response) cardiac damage. Acute myocarditis can present in various ways, and it may be a cause of sudden death in an otherwise healthy young adult. New treatments for viral heart disease are awaited. In the meanwhile, the haemodynamic support of patients with acute left ventricular failure caused by myocarditis should be aggressive, to allow for the possibility of spontaneous recovery. Contemporary trials of treatment in chronic heart failure secondary to dilated cardiomyopathy support the use of angiotensin converting enzyme inhibitors, beta adrenoceptor blockers, and spironolactone in such patients.     

糖心乐对糖尿病性心肌病大鼠血糖、血脂代谢的实验研究

目的:观察糖心乐(TXL)对糖尿病性心肌病(DCMP)大鼠血糖、血脂的影响。方法:SD大鼠随机分为正常对照组、模型对照组、达美康组及糖心乐大、小剂量组。将除正常对照组外的各组大鼠腹腔注射STZ建立糖尿病模型,造模后8w分别给予生理盐水、达美康、TXL大小剂量灌胃,连续4w,正常对照组不做处理。结果:与模型对照组比较,达美康组、糖心乐大、小剂量组大鼠的血糖、甘油三酯(TG)、总胆固醇(TC)显著降低(P<0.05,P<0.01),高密度脂蛋白(HDL-C)显著升高(P<0.05,P<0.01)。TXL大剂量组的降低血糖、TC,升高HDL-C作用与达美康组相当,降低TG作用优于达美康组(P<0.05)。结论:TXL可通过降低血糖、TG、TC水平,升高HDL-C水平来改善DCMP大鼠心肌的功能。     

经冠脉自体骨髓单个核细胞移植治疗扩张型心肌病的随机对照研究

目的采用随机、对照、前瞻性的临床试验,旨在评价经冠脉自体骨髓单个核细胞(BMMNCs)移植治疗扩张型心肌病的有效性和安全性。方法连续入选26例扩张型心肌病患者,细胞移植组(14例)行经冠脉自体BMMNCs移植联合标准药物治疗;对照组(12例)接受标准药物治疗。结果3个月后,细胞移植组的左室射血分数(LVEF)由(29.21±4.41)%提高至(31.08±4.54)%(P=0.004),与对照组比较,无统计学差异(P=0.216);PET/CT示心肌13N-NH3灌注和18F-FDG代谢显像显著改善;氮末端脑钠素前体(NT-proBNP)、6min步行试验和明尼苏达生活质量评分的改变均具有统计学意义。结论经冠脉自体BMMNCs移植治疗扩张型心肌病安全而有效,可能是通过BMMNCs转分化为心肌细胞和血管内皮细胞而改善心功能。     

自发性糖尿病大鼠心肌物质代谢及细胞增殖相关基因的表达谱研究

目的 研究自发性糖尿病（OLETF）大鼠发生心肌病变后基因表达谱的改变.方法 ①检测糖尿病大鼠与对照组大鼠的心室压,并比较两者的电镜标本;②从心肌组织中抽提纯化总RNA,逆转录合成两组动物的cDNA及cRNA探针,与基因表达谱芯片杂交,扫描并分析统计.结果 ①糖尿病大鼠的-dp/dt max,左室内压峰值明显小于对照组,EDP明显高于对照组;电镜提示糖尿病大鼠存在心肌肌纤维扭曲断裂,线粒体变性,间质增生及血管基底膜增厚;②糖尿病大鼠心肌中调控细胞增殖分化基因上调表达;胰岛素信号通路PI3K调节亚基基因及部分参与糖、脂代谢基因的表达明显下调.结论 糖尿病大鼠存在心肌超微结构改变和心肌舒张功能下降,表达谱中PI3K调节亚基及物质代谢、细胞增殖相关基因表达异常.     

左西孟旦与多巴酚丁胺治疗扩张型心肌病并顽固性终末期心衰的对比分析

目的对比左西孟旦与多巴酚丁胺治疗扩张型心肌病并顽固性终末期心衰的疗效。方法将2016年2月~2017年2月我院90例扩张型心肌病并顽固性终末期心衰患者采用数字表法分为两组,对照组予常规抗心衰和多巴酚丁胺治疗,观察组予常规抗心衰和左西孟旦治疗,比较两组的临床治疗效果及症状改善时间、心衰纠正时间;两组患者干预前后左室射血分数、左室舒张末期内径、脑钠肽、心脏指数、药物副作用发生率。结果观察组扩张型心肌病并顽固性终末期心衰治疗效果高于对照组(P0.05);观察组症状改善时间、心衰纠正时间短于对照组(P0.05);干预前两组左室射血分数、左室舒张末期内径、脑钠肽、心脏指数相近(P0.05);干预后观察组左室射血分数、左室舒张末期内径、脑钠肽、心脏指数优于对照组(P0.05)。两组药物副作用发生率比较,无显著差异(P0.05)。结论左西孟旦与多巴酚丁胺治疗扩张型心肌病并顽固性终末期心衰的对比,左西孟旦效果更好,可更快改善心功能、纠正心衰,且药物安全性较高,值得推广。