心房钠尿肽基因敲除小鼠的鉴定

研究心房钠尿肽基因敲除小鼠(ANP-/-小鼠)的生物学及病理学特性。ANP-/-小鼠与C57BL/6小鼠饲养于SPF级环境中,观察小鼠的繁育状况及其生物学特性,选取合适时间处死小鼠,通过HE染色观察脏器形态及组织结构。ANP-/-小鼠的繁殖周期比C57BL/6长,产仔率较低;ANP-/-小鼠肝脏、肺脏、脾脏较C57BL/6小鼠的有明显炎症反应,但是C57BL/6小鼠未见明显的病理改变。提示ANP基因的缺失可能与炎症发生有关。说明ANP-/-小鼠繁殖较慢、产仔率低,且正常繁殖的普通小鼠不会引起器官的病理学改变。但作为一种在心血管、代谢疾病上的动物模型,并与炎症甚至肿瘤有可能的未知联系的转基因动物,其很有研究和探索价值。     

p300/p53/Smad3 pathway involved in aging-related atrial fibrosis in human atrial fibroblasts

AIM To investigate the role of p300 in aging-related atrial fibrosis in human atrial fibroblasts （HAFs） and its potential mechanism. METHODS HAFs were obtained from human left atrial tissue, and the senescence model was established by cell passage. Senescence-associated β-galactosidase （SA-β-Gal） staining was used to detect the cell senescence, and Western blot was used to determine the protein levels of p300, p53, Smad3 and other senescence and fibrosis associated proteins in HAFs. RESULTS Compared to passage 3 HAFs, the proportion of senescent cells, and the protein levels of p300, p53, p-Smad3 and other senescence and fibrosis associated proteins were increased in HAFs at passage 7 and 11 （P<0.05）. After treated with curcumin （a p300 inhibitor） or transfection with p300 small-hairpin （sh） RNA plasmid, the protein levels of p300, and the senescence and fibrosis associated proteins were decreased in HAFs at passage 7（P<0.05）. Up-regulation of p300 by transfection with p300 over-expression plasmid increased the protein levels of p53, Smad3 and MMP-2 in HAFs at passage 3 （P<0.05）. CONCLUSION p300/p53/Smad3 signaling pathway plays an important role in aging-related atrial fibrosis in HAFs.     

Establishment of a Model of Spontaneously-Running-Tokushima-Shikoku Rats with Left Atrial Thrombosis

Studies that investigate the underlying mechanisms of disease and treatment options typically require the use of a suitable animal model. Few suitable animal models exist for left atrial thrombosis. Here, we demonstrated that the Spontaneously-Running-Tokushima-Shikoku (SPORTS) rat — a Wistar strain known for its running ability—is predisposed to the development of thrombi in the left atrium. We investigated the incidence of left atrial thrombosis in male (n = 16) and female (n = 17) SPORTS rats and observed organized atrial thrombosis in 57% and 38% of males and female rats, respectively. In the male rats, systolic blood pressures and heart rates were significantly higher in SPORTS rats than in control Wistar rats. We could not find any evidence of arrhythmias, such as atrial fibrillation, during electrocardiographic examination of SPORTS rats. We believe that the SPORTS rat could serve as a new research model for left atrial thrombosis; further, it may be suitable for research investigating the development of new antithrombotic approaches for the control of atrial thrombosis or familial thrombophilia in humans.     

Prognostic Value of Left Atrial Function in Dogs with Chronic Mitral Valvular Heart Disease

Background

A strong correlation between left atrial (LA) dysfunction and the severity of cardiac disease has been described in human patients with various cardiac diseases. The role of LA dysfunction in dogs with chronic mitral valvular heart disease (CMVHD) has not been addressed.

Objectives

To investigate the correlation between LA function and the prognosis of dogs with CMVHD.

Animals

Thirty‐eight client‐owned dogs with CMVHD.

Methods

Prospective clinical cohort study. Dogs were divided into 2 groups (survivors and nonsurvivors) based on the onset of cardiac‐related death within 1 year. Physical examination and echocardiographic variables were compared between the groups. For the assessment of the comparative accuracy in identifying patients with cardiac‐related death, receiver operating characteristic (ROC) curves and multivariate logistic analysis were used.

Results

The highest accuracy was obtained for the LA active fractional area change (LA‐FAC _act), with an area under the ROC curve (AUC) of 0.95, followed by the left atrial to aortic root ratio (LA/Ao), with an AUC of 0.94; peak early diastolic mitral inflow velocity (E), with an AUC of 0.85; and LA total fractional area change (LA‐FAC _total), with an AUC of 0.85. In the multivariate logistic regression analysis, LA‐FAC _act emerged as the only independent correlate of cardiac‐related death within 1 year (odds ratio = 1.401, P = .002).

Conclusions and Clinical Importance

Regarding both the size and function, the LA has a strong correlation with the prognosis of dogs with CMVHD. The most significant independent predictor of mortality in this study was LA‐FAC _act.     

Biochemistry and physiology of a family of eel natriuretic peptides

Three natriuretic peptides with similar structures were isolated from eels and their amino acid sequences determined; atrial natriuretic peptide (ANP) from atria, ventricular natriuretic peptide (VNP) from ventricles, and C-type natriuretic peptide (CNP) from brains. All three hormones were circulating in eel blood, and their plasma levels invariably decreased when eels were transferred from fresh water (FW) to seawater (SW). Eel ANP and VNP inhibited drinking in FW and SW eels. Eel ANP inhibited water and Na⁺ absorption by the intestine of SW eels. The potency of these ANP effects was 2–3 orders greater than those of other hormones which are known to have similar effects. Eel ANP and VNP induced antidiuresis but not antinatriuresis in FW eels. Eel ANP increased plasma cortisol level in SW eels but not in FW eels. The antidiuretic effect and the stimulation of cortisol secretion in eels are opposite to the ANP effects reported in mammals. These data suggest that ANP plays a complex role in the eel osmoregulation.

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Résumé Trois peptides natriurétiques présentant des structures similaires ont été isolés chez l'anguille et leurs séquences en acides aminés a été déterminées; le peptide atrial natriurétique (ANP) dans l'atria, le peptide ventriculaire natriurétique (VNP) dans les ventricules et le peptide natriurétique de type C dans le cerveau. Ces trois hormones sont présents dans le sang d'anguille et leur niveau plasmatique decroit invariablement quand les anguilles sont transférées d'eau douce en eau de mer. L'ANP et le VNP d'anguille inhibent l'action de boire chez les anguilles d'eau douce et d'eau de mer. L'ANP d'anguille inhibe l'absorption d'eau et de Na⁺ par l'intestin d'anguille en eau de mer. Ces effets de l'ANP sont 2 à 3 fois plus grands que ceux observés avec d'autres hormones qui sont connues pour avoir des effets similaires. L'ANP et le VNP d'anguille induisent l'antidiurèse mais pas l'antinatriurèse chez les anguilles d'eau douce. L'ANP d'anguille augmente chez ce poisson les niveaux de cortisol plasmatique en eau de mer mais pas en eau douce. L'effet antidiurétique et la stimulation de la sécrétion de cortisol chez l'anguille sont contraire aux effets de l'ANP observés chez les mammifères. Ces résultats suggèrent que l'ANP joue un role complexe dans l'osmorégulation de l'anguille.