Maternal influences on cardiovascular pathophysiology

Elevated blood pressure (BP) is of special clinical significance because of its association with pathophysiologies such as heart disease, renal failure, and stroke. We described the development of a protocol for use with hypertensive rats in which prepubertal exposure to a high salt (8% NaCl) diet results in a pathophysiological syndrome including rapid increase in BP, failure to maintain normal weight gain, renal damage, cerebrovascular lesions, and early mortality. These phenomena are described for the inbred spontaneously hypertensive rat (SHR), and for reciprocal F₁ hybrids of a cross between SHR and the Dahl salt-sensitive (SS/Jr) inbred strain. The study with reciprocal F₁s revealed striking effects of maternal environment on pathophysiological response to a high salt diet. F₁s nurtured by SHR mothers weighed less at 35 days of age, and after exposure to the high salt diet suffered more rapid BP increases, greater incidence of stroke, body weight loss, and mortality, than F₁s nurtured by SS/Jr dams. These results suggest that maternal mediation of the nutritional status of the animal may play an important role in determining susceptibility to elevated BP and subsequent pathophysiology associated with exposure to a high salt diet. The implication of these findings for human hypertension is briefly discussed.     

下肢静脉功能不全时下肢腓肠肌细胞病理生理学改变的研究

探讨腓肠肌细胞病理形态学和细胞代谢变化与下肢静脉功能不全相互关系及其临床意义 .依据血管造影和多普勒超声检查结果分为对照组 (A组 )及单纯下肢浅静脉曲张 (B组 )、原发性下肢深静脉瓣膜功能不全(C组 ) 3组 ,每组 1 0例 .分别取大腿长收肌 (对照 )和小腿腓肠肌标本检测肌肉中的SOD、NO、Na+ _K+ _ATP酶、Ca2 + _ATP酶、乳酸等各项指标 ;HE染色、ATP酶染色、SDH/COX双重染色后光镜、电镜观察 .结果显示 :A及B组肌组织结构和生化指标均正常 ,C组腓肠肌可见散在肌纤维萎缩、变性和坏死 ,炎性细胞浸润 ;同型肌纤维群化 ;COX/SDH染色可见单根或多根肌纤维酶活性增高 .肌丝间可见脂肪空泡聚集 ,部分线粒体空泡化或髓鞘样改变 .C组腓肠肌乳酸显著高于其他组别 (P <0 .0 1 ) ,而其Na_K_ATP酶、Ca2 + _ATP酶活性、NO、SOD等与其他组比较有显著下降 (P <0 .0 1 ) .表明下肢深静脉功能不全者患肢腓肠肌在肌纤维类型、超微结构和肌肉组织多项生化指标等均发生明显变化 ,推测小腿腓肠肌超微结构的病变是手术后远期效果不佳的病理基础 .如果从骨骼肌营养和抗氧化处理等角度进行治疗 ,可能会改善小腿肌肉泵功能     

FBXO6稳定表达肿瘤细胞系的构建及其亚细胞器定位

检测FBXO6在多种肿瘤细胞中的表达和定位情况并构建稳定表达FBXO6的肿瘤细胞株。运用RT-PCR方法,在人胚肾293T细胞以及9种不同来源的肿瘤细胞中,检测了FBXO6的表达情况。以载体质粒pBabe-3Flag-FBXO6-puro/pBabe-3Flag-con、包装质粒pCMV-GAG-POL及包膜质粒pCMV-VSVG用Lipofectamine2000共转染包装细胞系293T,收集病毒颗粒感染A549细胞,经嘌呤霉素筛选稳定表达细胞株,Western blot鉴定FBXO6的表达。利用激光共聚焦荧光显微镜,采用间接免疫荧光方法,检测外源性FBXO6在A549中的亚细胞定位。在10种不同来源的细胞株中,FBXO6在A549细胞中的表达最高。成功筛选出嘌呤霉素抗性细胞系A549-Con与A549-3Flag-FBXO6。Western blot方法发现A549-3Flag-FBXO6细胞系稳定表达FBXO6蛋白。间接免疫荧光发现FBXO6与内质网tracker有共定位。FBXO6在肺癌A549细胞中高度表达,构建了稳定表达FBXO6的A549细胞系,部分FBXO6分布在内质网中。     

Genetic models in brain and behavior research,part IV

Four reviews on the the role of developmental factors in hypertension are introduced and set in historical context. Recent research in the laboratory rat has shown that the preweaning environment makes an important contribution to the level of blod-pressure reached in adult life in genetic models of hypertension. Both of the most commonly used models of hypertension, the SHR and SS/Jr rat strains, exhibit lower BP in adult life, if they are fostered shortly after birth to mothers from their normotensive control strains. It has been suggested that it is the idiosyncratic maternal behavior of the hypertensive mothers which contributes to the elevated BP of their offspring, and it has been amply demonstrated that there is an association between a constellation of behaviors emitted by rat mothers and the adult BP of their offspring in a wide variety of genetic groups (inbred hypertensive animals, F1's and F2's). In addition to the above, maternal environment has been demonstrated to have a significant impact on the pathophysiological response of hypertensive animals to a high salt diet. Being raised by an SHR mother, versus an SS/Jr mother, increases the magnitude of BP increases to a high salt diet, susceptibility to hemorrhagic stroke, body weight loss and the risk of mortality. A variety of physiological systems are undergoing rapid change during the preweaning period and may mediate the effects of differences in the maternal environment. These include the renin-angiotensin system and the peripheral sympathetic nervous system. Nutritional factors may be involved in all of the phenomena referred to above. Thus, any physiological mechanisms that are proposed to link maternal behavior to its effects on the physiology of adult animals should recognize the involvement of nutritional factors. Research on the role of developmental factors such as maternal behavior in genetic models of hypertension is at the interface of two growing disciplines: behavior genetics and developmental psychobiology. The methodological and conceptual contributions of these fields to advancing our understanding of these phenomena is emphasized.     

基于NADH荧光的组织病理生理状态多参数在体监测与评价

组织病理生理状态的实时多参数评价, 无论在动物实验研究还是临床应用中均具有重要价值, 一直是生命科学与医学研究者们广泛关注的热点. 众所周知, 临床手术过程或重症监护病房中, 患者病理生理状态的实时监测是十分必需的. 心、脑等重要组织脏器是否处于缺血缺氧等危急状态直接关系到病人的存活与否; 早期发现术中和术后次要脏器的微循环障碍有助于提高器官移植等手术的成功率和降低术后并发症的发生率. 临床常规使用的监测指标, 如血压、心电、脉搏等, 在生命指征的实时评价中发挥了重要作用. 然而, 目前的常规指标尚不足以从分子水平反映局部组织病理生理状态的早期改变. NADH是细胞线粒体中氧化还原呼吸链上的内源性关键分子, 具有自发荧光性质, 可作为一项灵敏的内源性含氧状态指标来反映机体的代谢状态和细胞活力. 本文介绍了基于NADH自发荧光信号的细胞氧化还原状态在体监测方法, 从分子水平预警机体的活力情况, 结合微循环血流、血氧饱和度等多种生理参数的同步并行监测, 不仅可在活体动物体内进行疾病的病理生理学机制研究和新药的药效评价, 还有望应用于临床外科手术和重症监护病房, 为机体活力和生命指征的实时监护提供分子水平的动态信息. 目前, NADH荧光一维信号的获取技术发展最为成熟, 可实现从离体、活细胞、活体动物乃至临床水平的实时动态监测, 已处于临床推广应用阶段. 二维动态成像也已经发展到活体动物实验阶段. 三维成像由于受制于NADH荧光的穿透能力, 只能在冷冻组织切片上实现. 如何突破因高散射所致的荧光穿透能力受限的瓶颈, 最大限度地减少环境因素对荧光信号的干扰, 在分子水平实现组织病理生理状态的实时多参数评价, 是生物医学光子学领域面临的巨大挑战.     

浅谈如何提高学生在病理生理学课堂上的主观能动性

病理生理学是一门难教难学的重要医学基础理论课程。课堂是教师教授和学生学习的主要阵地。教师需不断丰富完善自身知识体系，在课堂上运用灵活的教学方法，利用科学先进的教学手段，努力激发学生对病理生理学的学习热情，开发学生学习的主观能动性，提高学生的课堂学习效果，并培养学生将理论应用于实践的临床思维能力。     

Synaptic dysfunction in Huntington’s disease: a new perspective

Huntington’s disease (HD) is caused by a polyglutamine expansion in the protein huntingtin and is characterized by intraneuronal inclusions and widespread neuronal death at the late stage of the disease. In research, most of the emphasis has been on understanding the cell death and its mechanisms. Until recently, it was believed that the vast majority, if not all, of the symptoms in HD are a direct consequence of neurodegeneration. However, increasing evidence shows that subtle alterations in synaptic function could underlie the early symptoms. It is of particular interest to understand the nature of this neuronal dysfunction. Normal huntingtin interacts with various cytoskeletal and synaptic vesicle proteins that are essential for exocytosis and endocytosis. Altered interactions of mutant huntingtin with its associated partners could contribute to abnormal synaptic transmission in HD. This review describes recent advances in understanding synaptic dysfunction in HD.Received 2 March 2005; received after revision 13 April 2005; accepted 19 April 2005