Combined administration of lauric acid and glucose improved cancer‐derived cardiac atrophy in a mouse cachexia model

Cancer‐derived myocardial damage is an important cause of death in cancer patients. However, the development of dietary interventions for treating such damage has not been advanced. Here, we investigated the effect of dietary intervention with lauric acid (LAA) and glucose, which was effective against skeletal muscle sarcopenia in a mouse cachexia model, on myocardial damage. Treatment of H9c2 rat cardiomyoblasts with lauric acid promoted mitochondrial respiration and increased ATP production by Seahorse flux analysis, but did not increase oxidative stress. Glycolysis was also promoted by LAA. In contrast, mitochondrial respiration and ATP production were suppressed, and oxidative stress was increased in an in vitro cachexia model in which cardiomyoblasts were treated with mouse cachexia ascites. Ascites‐treated H9c2 cells with concurrent treatment with LAA and high glucose showed that mitochondrial respiration and glycolysis were promoted more than that of the control, and ATP was restored to the level of the control. Oxidative stress was also reduced by the combined treatment. In the mouse cachexia model, myocardiac atrophy and decreased levels of a marker of muscle maturity, SDS‐soluble MYL1, were observed. When LAA in CE‐2 diet was orally administered alone, no significant rescue was observed in the cancer‐derived myocardial disorder. In contrast, combined oral administration of LAA and glucose recovered myocardial atrophy and MYL1 to levels observed in the control without increase in the cancer weight. Therefore, it is suggested that dietary intervention using a combination of LAA and glucose for cancer cachexia might improve cancer‐derived myocardial damage.     

Epicardium is required for sarcomeric maturation and cardiomyocyte growth in the ventricular compact layer mediated by transforming growth factor β and fibroblast growth factor before the onset of coronary circulation

The epicardium, which is derived from the proepicardial organ (PE) as the third epithelial layer of the developing heart, is crucial for ventricular morphogenesis. An epicardial deficiency leads to a thin compact layer for the developing ventricle; however, the mechanisms leading to the impaired development of the compact layer are not well understood. Using chick embryonic hearts, we produced epicardium‐deficient hearts by surgical ablation or blockade of the migration of PE and examined the mechanisms underlying a thin compact myocardium. Sarcomeric maturation (distance between Z‐lines) and cardiomyocyte growth (size) were affected in the thin compact myocardium of epicardium‐deficient ventricles, in which the amounts of phospho‐smad2 and phospho‐ERK as well as expression of transforming growth factor (TGF)β2 and fibroblast growth factor (FGF)2 were reduced. TGFβ and FGF were required for the maturation of sarcomeres and growth of cardiomyocytes in cultured ventricles. In ovo co‐transfection of dominant negative (dN)‐Alk5 (dN‐TGFβ receptor I) and dN‐FGF receptor 1 to ventricles caused a thin compact myocardium. Our results suggest that immature sarcomeres and small cardiomyocytes are the causative architectures of an epicardium‐deficient thin compact layer and also that epicardium‐dependent signaling mediated by TGFβ and FGF plays a role in the development of the ventricular compact layer before the onset of coronary circulation.     

儿童心肌致密化不全的临床表现及预后

心肌致密化不全是一种与基因相关的遗传性心肌病,以心室内异常粗大的肌小梁和交错的深隐窝为特征.心肌致密化不全病因及发病机制不清.心肌致密化不全临床少见,预后较差.该文就儿童心肌致密化不全的临床表现及预后进行阐述,加深对儿童心肌致密化不全的认识,提高临床诊治水平,提高患者生存质量,延长患儿生存期.     

主动脉-左心室隧道并心内多发畸形1例病例报道

主动脉-左心室隧道(Aorto-Left Ventricular Tunnel,ALVT)是指升主动脉根部与左心室之间存在主动脉瓣旁的异常通道,1963年Levy等首先命名及报道该病[1]。ALVT是一种罕见的先天性心脏病,仅占先天性心脏病的0．05%～0．12%,可伴主动脉瓣二叶畸形、主动脉瓣狭窄或( 和) 关闭不全等,以及合并其他心血管畸形［2－4］。现将我院超声心动图首诊为ALVT的1例患儿的超声心动图特征并结合文献进行总结分析,探讨超声心动图对主动脉-左心室隧道诊断的价值。     

急性心肌梗死热毒证候病因探讨回顾性分析

目的:探讨急性心肌梗死热毒证患者的危险因素,对其证候病因进行分析。方法:回顾性筛选收集广州中医药大学第一附属医院确诊为急性心肌梗死患者的临床资料,进行中医证候分布调查,并将其分为热毒证组及非热毒证组,分析两组的一般资料以及住院病情预后,并采用Logistic回归分析热毒证病因的危险因素。结果:研究纳入322例患者中热毒证组占42.20%(136例),非热毒证组占57.8%(186例)。热毒证组平均血管病变数、左室舒张末、左室射血分数明显差于非热毒组(P0.05),住院期间心血管死亡例数两组未见明显差异。单因素分析热毒证分布为吸烟、辛辣厚味饮食、糖尿病、高脂血症多重心血管危险因素聚集人群(P0.05),Logistic回归分析发现吸烟、低密度脂蛋白、甘油三酯3个因子是预测热毒证候病因的独立要素,比值比(OR)分别为1.755,1.637,1.483。结论:急性心肌梗死热毒证形成病因与吸烟、血脂代谢紊乱相关,住院期间预后与非热毒证未见差异,但心室重构程度重于非热毒证组。     

外源性磷脂酸对心室肌细胞钙电流的作用

目的：观察外源性磷脂酸（PA）对豚鼠心室肌细胞钙电流的影响。方法：Langendorff离体心脏逆向灌流法分离豚鼠心室肌细胞,随机选取心室肌细胞分为： 正常对照组,PA 0.01、0.1和1.0 μmol·L^-13个剂量组,百日咳毒素（PTX）0.1 mg·L^-1+PA 1.0 μmol·L^-1组,蛋白激酶C(PKC)阻断剂H-7 2 μmol·L^-1+PA 10　μmol·L^-1组。应用全细胞电压钳方法分别记录各组心室肌细胞Ca²⁺电流。结果：外源性PA 0.01、 0.1 和1 mmol·L^-1分别使豚鼠心 室肌细胞L-型钙电流（L-I_Ca）由给药前的（288.70±28.33）、（290.83±25.12）和 （279.54±31.22）pA增加到给药后的（304.10±28.31）（P>0.05）、（349.80±30.13）(P<0.01)和（388.10±28.12）pA(P<0.001);加入G-蛋白耦联受体阻断剂PTX和PKC阻断剂H-7后,PA对²⁺通道电流的作用与给药前比较差异无显著性。结论：外源性PA可增加豚鼠心室肌细胞的L-I_Ca电流,其作用机制是通过膜受体-G蛋白-PKC通路发挥作用。     

葛根素对儿茶酚胺诱导大鼠心肌损伤时凋亡相关蛋白的影响

目的 :探讨在儿茶酚胺诱导的心肌损伤过程中 ,心肌细胞的凋亡相关基因 Fas和 Bcl 2的蛋白表达改变及葛根素干预的影响。方法 :5 0只健康雄性 SD大鼠随机分成 3组 :心肌损伤组 (2 0只 )、葛根素干预组 (2 0只 )和对照组 (10只 )。动物模型仿用异丙肾上腺素 (ISO)皮下注射致心肌损伤方法。心肌组织切片分别行 HE及 Fas和 Bcl 2蛋白表达的免疫组织化学染色检测。结果 :心肌损伤组 :Fas蛋白和 Bcl 2蛋白的表达等级均上调 (P均 <0 .0 0 1) ,Fas蛋白的表达水平更高 (P<0 .0 0 1)。葛根素干预组 :心肌组织的 HE病理损害等级明显减轻 (P<0 .0 5 ) ;Fas蛋白表达等级下调 (P<0 .0 5 )。结论 :在儿茶酚胺诱导的心肌损伤过程中 ,Fas和 Bcl 2的蛋白表达水平表现出高水平的差异 ,葛根素能抑制损伤过程中 Fas蛋白的表达。