显微磁共振成像在神经精神疾病模型动物在体研究中的应用

妻人体的复杂性决定了大量疾病的研究工作要通过动物模型在体动态研究来实现.显微磁共振成像技术的发展及其在人类神经精神疾病动物模型中的应用,从在体神经解剖信息到特定分子靶点的测定,为推动神经精神病学研究的深入和发展开辟了新的途径.     

硒锰锌与心肌损伤的实验研究

用低Ｓｅ高Ｍｎ人工半合成饲料喂饲大白鼠，复制动物心肌损伤模型。补充Ｓｅ（０．３ｍｇ／ｋｇ）或Ｚｎ（２００ｍｇ／ｋｇ），以观察Ｓｅ或／和Ｚｎ对心肌损伤的影响。实验结果表明，单纯补充Ｓｅ或Ｚｎ均能不同程度降低心肌细胞膜的通透性，提高心肌ＣＣＯ和ＳＤＨ活性，心肌坏死检出率和坏死因面积均有降低缩小的趋势。同时补Ｓｅ和Ｚｎ上述两种酶活性提高较显著，心肌坏死检出率最低，坏死面积最小。     

依那普利对放射性心肌损伤cTnT的影响

目的观察放射性心肌损伤后血清肌钙蛋白T(cTnT)的变化及依那普利对cTnT的影响,了解依那普利对心肌的保护作用.方法利用放射性心肌损伤大鼠模型,比较单纯照射组、依那普利组、正常对照组cTnT、血清肌酸激酶同工酶(CK-MB)变化,分别测定照射后第3天、第7天、第1 4天、第2 1天的血清cTnT及CK-MB水平.结果单纯照射组与对照组比较,cTnT从第3天开始增高,以第7天增高最明显,第14天渐降,第21天降至正常.CK-MB在第3天、第7天增高,第14天、第21天均正常.依那普利组与对照组比较cTnT仅第3天增高;CK-MB第3天、第7天增高,余无差别.依那普利组与单纯照射组比较cTnT漏出明显减少,第3天已明显降低,第7天、第1 4天显著降低,第21天无差别.CK-MB第3天无差别、第7天明显降低.结论cTnT较CK-MB对放射性心肌损伤的诊断具有更高的特异性、敏感性和更长的诊断时间窗,并能反映心肌损伤的程度.依那普利对放射性心肌损伤有明显的保护作用.     

心肌肌钙蛋白Ⅰ与心肌损伤

<正> 急性心肌损伤是威胁人类生命的主要疾病之一,人们一直在探索和寻求对其诊断灵敏度高、特异性好的指标.最近几年来关于心肌结构蛋白的研究初步表明:心肌肌钙蛋白I(cTnI)是心脏特异性抗原,当心肌细胞损伤时,在血中出现的时间早,持续时间长,因而引起了研究者的广泛兴趣.     

地尔硫唑对放射损伤心肌的保护作用

目的观察放射损伤心肌血清肌钙蛋白T（cTn-T）含量和血清肌酸激酶（CK-MB）活性及心肌超微结构钙颗粒的变化及药物地尔硫唑的影响,了解地尔硫唑对心肌的保护作用。方法30只Wistar大鼠,正常及放射损伤心肌模型的大鼠分3组,即单纯照射组、照射给药组、对照组,观察照射后3、7、14、21 d的血清cTn-T含量及CK-MB活性和34 d心肌细胞的钙颗粒分布特点与超微结构变化。结果单纯照射组与对照组比较cTn-T的含量3 d开始增高,以7 d增高最明显,14 d渐降。CK-MB活性在3、7 d增高,14、21 d均恢复正常。心肌超微结构主要改变为肌丝排列紊乱、局灶性溶解;核染色质边集;线粒体肿胀、嵴不清、嵴断裂、空泡化;钙颗粒在线粒体膜完整的明显增多,线粒体破坏的消失,可见线粒体钙化。照射给药组与对照组比较cTn-T3、7、14 d均增高;CK-MB 3、7 d增高,余无差别。心肌肌原纤维收缩态多于舒张态,肌丝排列紊乱,有轻微的局灶性溶解;核染色质轻度边集;线粒体明显肿胀,嵴断裂,空泡,线粒体外钙颗粒增多。照射给药组与单纯照射组比较cTn-T3 d增高,7、14 d漏出明显减少,CK-MB 7 d增高,cTn-T酶峰前移。心肌线粒体肿胀、空泡化以及肌溶解明显减轻,钙沉积减少。结论cTn-T含量较CK-MB活性能较好地反映心肌损伤的程度,是放射损伤心肌较理想的诊断指标。地尔硫唑对放射性心肌损伤有一定的保护作用,其机制与减轻心肌细胞内钙超载有关。     

体外循环心肌损伤及心肌保护的研究进展

人工心肺体外循环(ECC)是一项比较成熟的心外科生命支持技术,ECC的发明使切开心脏和大血管进行直视手术成为可能。但ECC诱发的心脏等重要脏器的损伤是除手术效果外影响患者预后的决定性因素,严重者会对手术患者的预后造成显著影响。尽管在过去几十年里,随着ECC保护措施的进步,使ECC后心肌等重要脏器的损伤显著下降,但是ECC自身的技术特点决定了ECC导致的心功能下降仍然存在。本综述浅述了ECC诱导心肌损伤的部分病理机制以及降低心肌损伤的可行措施。     

心肌损伤标志物在肺炎患儿中的意义研究

目的分析小儿肺炎心肌损伤标志物活性改变及其临床意义。方法肺炎组44例（重症组9例、轻症组35例）,对照组体检正常儿42例,检测心肌酶（谷草转氨酶AST、α-羟丁酸脱氢酶、α-HBDH、肌酸磷酸激酶同工酶CK-MB）,肌钙蛋白I（CTNI）、肌红蛋白（MYO）活性,进行3组间心肌损伤标志物活性值比较。结果肺炎组患儿的各项心肌损伤标志物均高于正常对照组;重症肺炎组患儿CTnI升高6例,CK-MB升高5例,而轻症肺炎组患儿及正常对照组小儿CTnI值在正常范围内,轻症肺炎组患儿CK-MB升高15例。肺炎组患儿治疗前后心肌损伤标志物的变化,以MYO恢复最快（约起病后1周）,其他依次为α-HBDH、CTNI、AST、CK-MB。结论小儿肺炎时心肌损伤标志物活性呈不同程度增高,以AST活性增高最常见;重症肺炎时常有2项或3项心肌损伤标志物活性同时增高;但以CTNI特异性最高,CK-MB敏感性最高。     

天麻素在铁诱导的大鼠离体心肌损伤中的保护作用

目的观察天麻素在铁诱导的大鼠离体心肌损伤中的保护作用。方法应用Langendorff离体心脏灌流系统,灌注Fe-HQ建立铁诱导的离体心肌损伤模型。SD大鼠随机分成4组:正常组、Fe-HQ组、天麻素(0.1、0.025 mmol/L)组。观察天麻素对心率(HR)、左室收缩压(LVSP)、dp/dt max、冠脉流量(CF)的影响;测定冠脉流出液中的乳酸脱氢酶(LDH)及肌酸激酶(CK)的含量和心肌中丙二醛(MDA)的浓度;观察心肌组织的超微结构。结果天麻素能抑制铁诱导的心肌的HR、LVSP、dp/dt max、CF的下降;降低冠脉流出液中LDH和CK的含量及心肌中MDA的浓度。结论天麻素可改善铁诱导的心肌收缩功能和脂质过氧化,对铁诱导的大鼠离体心肌损伤有显著的保护作用。     

心肌代谢障碍与过氧化物酶体增殖激活受体

过氧化物酶体增殖激活受体在细胞能量代谢中起重要作用。既往的研究表明在各种心肌病变中均有不同程度的心肌能量代谢障碍,心肌细胞脂肪酸和葡萄糖的代谢失衡可能是心脏功能恶化的病理生理基础。近年来随着基因敲除和基因过表达技术的发展为我们了解心脏过氧化物酶体增殖激活受体的功能提供了更为方便、独特的途经,现对这一方面的进展作一综述。     

氨基末端脑钠肽前体对新生儿肺炎心肌损伤的诊断价值

目的 探讨新生儿肺炎并发心肌损伤时血中氨基末端脑钠肽前体（NT-proBNP）水平的变化,以及在不同胎龄儿中表达水平的差异,为新生儿肺炎并发心肌损伤提供早期诊断的可靠实验室指标.方法 将临床诊断为新生儿肺炎的患儿102例分为心肌损伤组和非心肌损伤组,入院第2、5天采用电化学发光法分别检测血中NT-proBNP水平,入院第5天同时检测肌酸激酶同功酶（CK-MB）、心肌肌钙蛋白T（cTnT）水平,比较两组患者NT-proBNP、CK-MB和cTnT的差异;同时分析不同胎龄儿血中NT-proBNP水平的差异.结果 新生儿肺炎第2天心肌损伤组和非心肌损伤组NT-proBNP值分别为（1203±362）pg/ml和（675±294）pg/ml,两组比较差异有统计学意义（P＜0.05）.第5天心肌损伤组和非心肌损伤组NT-proBNP值分别为（1893±475）pg/ml和（1075±330）pg/ml,两组比较差异有统计学意义（P＜0.05）.第5天心肌损伤组和非心肌损伤组cTnT值分别为（0.31±0.16）μg/L和（0.05±0.02）μg/L,两组比较差异有统计学意义（P＜0.05）;CK-MB两组间比较差异无统计学意义（P＞0.05）.不同胎龄儿中NT-proBNP值以早产儿最高,早产儿NT-proBNP值为（1428±407）pg/ml,三组比较差异有统计学意义（P＜0.05）.结论 新生儿肺炎发生心肌损伤时血氨基末端脑钠肽前体明显升高,可作为早期诊断的可靠实验室指标.不同胎龄儿中以早产儿NT-proBNP的血中基础值最高.     

Hypoxaemia and Myocardial Ischaemia during Colonoscopy

Background: Myocardial ischaemia (defined as ST-segment deviation on electrocardiogram (ECG)) may occur during colonoscopy, but the pathogenic mechanisms are unknown. We have evaluated the occurrence of arterial hypoxaemia, tachycardia, and myocardial ischaemia during routine colonoscopy. Methods: Eighteen patients underwent colonoscopy under conscious sedation and without supplementary oxygen. Arterial oxygen saturation was measured by continuous pulse oximetry, and ECG was monitored continuously with a Holter tape recorder during the procedure. Results: Arterial oxygen desaturation and tachycardia were common during colonoscopy and occurred in 45% and 35% of patients, respectively. Two patients developed signs of myocardial ischaemia during the colonoscopy: one case of ST depression (1.7 mV) and one case of ST elevation (4.3 mV). In both patients the ST deviation disappeared when the colonoscope was retracted. Myocardial ischaemia occurred in both patients simultaneously with tachycardia, and in one of these arterial hypoxaemia was also present. Conclusions: Myocardial ischaemia occurs during routine colonoscopy, but with a lower incidence than previously reported during upper endoscopy. Myocardial ischaemia during colonoscopy may be associated with tachycardia and/or hypoxaemia. Further studies should clarify the relative role of tachycardia, hypoxaemia, and viscerocardiac reflexes in the pathogenesis of myocardial ischaemia during colonoscopy     

Current In Vitro and In Vivo Models to Study MCPyV-Associated MCC

Merkel cell polyomavirus (MCPyV) is the only human polyomavirus currently known to cause human cancer. MCPyV is believed to be an etiological factor in at least 80% of cases of the rare but aggressive skin malignancy Merkel cell carcinoma (MCC). In these MCPyV+ MCC tumors, clonal integration of the viral genome results in the continued expression of two viral proteins: the viral small T antigen (ST) and a truncated form of the viral large T antigen. The oncogenic potential of MCPyV and the functional properties of the viral T antigens that contribute to neoplasia are becoming increasingly well-characterized with the recent development of model systems that recapitulate the biology of MCPyV+ MCC. In this review, we summarize our understanding of MCPyV and its role in MCC, followed by the current state of both in vitro and in vivo model systems used to study MCPyV and its contribution to carcinogenesis. We also highlight the remaining challenges within the field and the major considerations related to the ongoing development of in vitro and in vivo models of MCPyV+ MCC.     

Catecholamine Excretion with Myocardial Ischaemia and Infarction

Serial daily estimations were made of the urinary catecholamine excretion in 64 patients during the first two weeks after the onset of myocardial infarction and in 27 patients after the onset of chest pain subsequently diagnosed as myocardial ischaemia. In most patients with myocardial infarction, the total excretion rate of catecholamines was elevated, mainly due to elevation of the noradrenaline excretion rate. The level of catecholamine excretion correlated well with the peak levels of S.G.O.T., LD.H. and w.e.e. Higher levels of all these variables were found in patients with cardiac failure, hypotension and ventricular arrhythmias. On the other hand, catecholamine excretion, enzyme levels and wee were only slightly elevated in the patients with sinus or nodal bradycardia, and catecholamine excretion was barely elevated in patients who suffered chest pain without infarction. Thus, catecholamine excretion after myocardial infarction correlates with the degree of cardiac damage, functional impairment and the incidence of some arrhythmias. It is concluded that the increased catecholamine excretion originates from the sympathetic nerve endings as a reflex result of the haemodynamic disturbance, with some possible contribution from the sympathetic endings in the damaged heart muscle.     

Quercetin Prevents In Vivo and In Vitro Myocardial Hypertrophy Through the Proteasome-GSK-3 Pathway

Purpose

Quercetin, a flavonoid, has been reported to ameliorate cardiovascular diseases, such as cardiac hypertrophy. However, the mechanism is not completely understood. In this study, a mechanism related to proteasome-glycogen synthesis kinase 3 (GSK-3) was elucidated in rats and primary neonatal cardiomyocytes.

Methods

Rats were subjected to sham or constriction of abdominal aorta surgery groups and treated with or without quercetin for 8 weeks. Angiotensin II (Ang II)-induced primary cardiomyocytes were cultured with quercetin treatment or not for 48 h. Echocardiography, real-time RT-PCR, histology, immunofluorescence, and Western blotting were conducted. Proteasome activities were also detected using a fluorescent peptide substrate.

Results

Echocardiography showed that quercetin prevented constriction of abdominal aorta-induced cardiac hypertrophy and improved the cardiac diastolic function. In addition, quercetin also significantly reduced the Ang II-induced hypertrophic surface area and atrial natriuretic factor (ANF) mRNA level in primary cardiomyocytes. Proteasome activities were obviously inhibited in the quercetin-treated group both in vivo and in vitro. Quercetin also decreased the levels of proteasome subunit beta type (PSMB) 1, PSMB2, and PSMB5 of the 20S proteasome as well as the levels of proteasome regulatory particle (Rpt) 1 and Rpt4 of the 19S proteasome. In particular, the PSMB5 level in the nucleus was reduced after quercetin treatment. Furthermore, phosphorylated GSK-3α/β (inactivation of GSK-3) was decreased, which means that GSK-3 activity was increased. The phosphorylation levels of upstream AKT (PKB (protein kinase B)) and liver kinase B1/AMP activated protein kinase (LKB1/AMPKα) and those of downstream extracellular signal-regulated kinase (ERK), histone H3, β-catenin, and GATA binding protein 4 (GATA4) were reduced after quercetin treatment, while hypertrophy was reversed after treatment with the GSK-3 inhibitor.

Conclusion

In summary, quercetin prevents cardiac hypertrophy, which is related to proteasome inhibition and activation of GSK-3α/β. Upstream (AKT, LKB1/AMPKα) and downstream hypertrophic factors, such as ERK, histone H3, β-catenin, and GATA4, may also be involved.

     

Three-Dimensional Myocardial Contrast Echocardiography: Validation of In Vivo Risk and Infarct Volumes

Objectives. The aim of this study was to determine whether three-dimensional (3D) myocardial contrast echocardiography (MCE) could provide an accurate in vivo assessment of risk and infarct volumes.

Background. MCE has been shown to accurately define risk area and infarct size in single tomographic slices. The ability of this technique to measure risk and infarct volumes by using three-dimensional echocardiography (3DE) has not been determined.

Methods. Fifteen open chest dogs underwent variable durations of coronary artery occlusion followed by reperfusion. At each stage, MCE was performed by using left atrial injection of AIP201, a deposit microbubble with a mean diameter of 10 ± 4 μm and a mean concentration of 1.5·10⁷·ml⁻¹. Images were obtained over a 180° arc with use of an automated rotational device and were stored in computer as a 3D data set. Postmortem risk area and infarct size were measured in six to eight left ventricular short-axis slices of equal thickness using technetium-99m autoradiography and tissue staining, respectively. MCE images corresponding to these planes were reconstructed off-line.

Results. A close linear relation was noted between the volume of myocardium not showing contrast enhancement on 3D MCE during coronary occlusion and postmortem risk volume (y = 1.2x − 3.0, r = 0.83, SEE = 5.1, n = 15). The volume of myocardium not showing contrast enhancement on 3D MCE after reperfusion also closely correlated with postmortem infarct volume (y = 1.1x − 3.9, r = 0.88, SEE = 4.8, n = 11). No changes in systemic hemodynamic variables were noted with injections of AIP201.

Conclusions. When combined with AIP201, a deposit microbubble, 3D MCE can be used to accurately determine both risk and infarct volumes in vivo. This method could be used to assess the effects of interventions that attempt to alter the infarct/risk volume ratio.     

In Vivo and In Vitro Effects of Vasopressin V2 Receptor Antagonism on Myocardial Fibrosis in Rats

Background

Myocardial fibrosis is a major pathophysiologic substrate of heart failure with preserved ejection fraction. Vasopressin is an important therapeutic target in heart failure with preserved ejection fraction since it can modulate fluid balance, and based on a few studies, myocardial matrix deposition. Hence we examined the role of vasopressin antagonism in modulating myocardial matrix metabolism in vivo and in vitro.

Animal Models of Dyssynchrony

Cardiac resynchronization therapy (CRT) is an important therapy for patients with heart failure and conduction pathology, but the benefits are heterogeneous between patients and approximately a third of patients do not show signs of clinical or echocardiographic response. This calls for a better understanding of the underlying conduction disease and resynchronization. In this review, we discuss to what extent established and novel animal models can help to better understand the pathophysiology of dyssynchrony and the benefits of CRT.     

Animal Models of Osteonecrosis

Osteonecrosis is an uncommon but significant musculoskeletal disease characterized by focal areas of dead bone that often fail to heal even with intervention and has the potential to negatively impact a patient’s quality of life. The knee and hip seem to be most susceptible to osteonecrosis although certain conditions, such as bisphosphonate treatment, have been associated with the development of osteonecrosis that is confined to the jaw. For most types of osteonecrosis, there remains much to be learned about either the pathophysiology of disease or the best course of treatment—questions that are best approached using an animal model. The different etiologies of the subclasses of osteonecrosis have led to a diverse number of animal models within the field. While no one animal model completely simulates all aspects of a particular type of osteonecrosis, models do exist that mimic various clinical aspects of osteonecrosis. This review discusses aspects of the common and novel animal models used to study juvenile osteonecrosis (Legg-Calvé-Perthes), trauma-induced osteonecrosis, alcohol- and corticosteroid-induced osteonecrosis, and osteonecrosis of the jaw associated with anti-remodeling drug treatment.     

In Vivo Platelet Hyperactivity and Factor VIII Related Antigen Increase Long after Myocardial Infarction

In the Anturane Reinfarction Italian Study the trend of some specific and quantitative haemostatic parameters is being investigated in different series of patients balanced for sulfinpyrazone and placebo. In a series of young male patients who had had myocardial infarction 6 months previously, it has been shown that the placebo treatment subsample presented shortened platelet production time (PPT), increased levels of plasma β-thrombo-globulin (β-TG) and platelet factor 4 (PF₄), and increased factor VIII related antigen (VIII:RAg) compared with a matched control group. A close correlation between plasma concentration of VIILRAg and PPT was evidenced in the same treatment subsample. The sulfinpyrazone treatment subsample presented normalized PPT accompanied by reduction of VIII:RAg but not of β-TG or PF₄ levels.