高脂饮食对模拟低氧环境SD大鼠肺组织eNOS/NO的影响

目的 探讨高脂饮食对模拟低氧环境SD大鼠肺组织内皮型一氧化氮合酶（eNOS）/一氧化氮（NO）的影响及其可能机制.方法 雄性SD大鼠60只随机分为3组：常氧组、低氧组和低氧联合高脂饮食组,经普通饮食或高脂饮食4周后,留取外周血及肺组织标本,采用全自动血细胞分析仪检测静脉血血红蛋白（Hb）浓度,TBA比色法检测血浆丙二醛（MDA）含量,WST-1法检测超氧化物歧化酶（SOD）活力,终点法和直接检测法检测血脂含量,荧光实时定量PCR检测肺组织eNOS mRNA水平,Western blot法检测肺组织eNOS 蛋白表达水平,硝酸还原酶法检测肺组织NO代谢产物硝酸盐/亚硝酸盐（NOX）水平.结果 与低氧组比较,低氧联合高脂饮食组肺组织中eNOS mRNA表达水平明显升高,蛋白表达水平无明显变化,NOX含量明显降低,血浆TCH及LDL水平明显升高;低氧联合高脂饮食组血浆SOD活力及MDA含量低于低氧组.结论 高脂饮食降低低氧环境大鼠肺组织NOX水平,提示高脂饮食可引起慢性重度低氧环境下的肺组织损伤,其机制可能与血脂异常及抗氧化应激能力不足有关.     

血管内皮细胞EA．hy926对单核细胞U937清道夫受体表达的影响

[目的]研究单核细胞、内皮细胞的相互作用对单核细胞清道夫受体AI、CD36表达的影响,观察细胞因子在其中的介导作用。[方法]采用单核细胞U937、内皮细胞EA．hy926单独培养、隔离培养及混合培养的方法形成不同的培养条件,通过夹心酶联免疫吸附法检测培养液中巨噬细胞集落刺激因子的含量,使用流式细胞术检测单核细胞表面清道夫受体AI、CD36的表达程度。[结果]单核细胞单独培养条件下清道夫受体AI和CD36的表达量较低,在和内皮细胞隔离培养及混合培养后两者的表达量均显著性升高（P〈0．05）,巨噬细胞集落刺激因子和血小板源性生长因子BB在单核细胞清道夫受体AI和CD36表达增高的调节中起着一定的介导作用,但不占主要地位。[结论]单核细胞与内皮细胞的相互作用可通过多种环节上调单核细胞清道夫受体AI和CD36的表达,从而参与动脉粥样硬化的发展。     

Bone marrow cell therapies for endothelial repair and their relevance to kidney disease

Endothelial injury is a characteristic finding in chronic kidney disease and is associated with both markedly increased cardiovascular risk and chronic kidney disease progression. The past decade has seen a remarkable surge of interest in the role of bone marrow-derived cells for the protection, repair, and regeneration of injured endothelium. In particular, despite controversies regarding their mechanisms of action, endothelial progenitor cells have garnered considerable attention, with multiple reports suggesting that these cells exhibit remarkable pro-angiogenic effects. Recent advances in our understanding of how the bone marrow responds to endothelial injury now suggest that multiple bone marrow cell populations, including both endothelial progenitor cells and a novel group of cells called early outgrowth cells, promote endothelial repair and regeneration through different, yet complementary, mechanisms. Moreover, certain subsets of bone marrow-derived cells also appear to have novel, potent, angiogenesis-independent tissue-protective properties. The bone marrow should thus now be viewed not only as a hematopoiesis organ, but also as a rich reservoir of cells capable of protecting and even regenerating nonhematopoietic tissues such as the kidney. To harness the prognostic and therapeutic potential of the bone marrow, the renal community must be aware of recent advances in our understanding of the nature and therapeutic potential of these cells.     

Endothelium under stress: local and systemic messages

Endothelial responses to stressors are nonuniform and follow the rules of stress-induced hormesis. Responses to the same stressor, depending on its intensity, can range from pro-regenerative to pro-lethal. Exposure to sublethal stressors induces a programmed response that results in stress resistance, whereas a lethal level of a stressor accelerates cell demise. Diverse stressors turn on several default programs within the cells; such programs tend to induce anti-oxidative defenses and anti-inflammatory and pro-survival systems, whereas others tend to switch on pro-apoptotic systems. The response of the kidney endothelium to various forms of acute kidney injury follows these general principles. It is characterized by a proinflammatory pattern that includes up-regulation of different adhesion molecules promoting endothelial-leukocyte interactions, generation of reactive oxygen species, with formation of oxidative and nitrosative stress and mitochondrial damage. Simultaneously, a series of adaptive mechanisms, both local and systemic, are ignited. Stressed endothelial cells broadcast distress signals systemically; these signals can be directed toward the restoration of homeostasis or aggravation of the original insult.     

Targeted therapies in pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH) is a rare disorder characterized by progressive obliteration of small pulmonary arteries that leads to elevated pulmonary arterial pressure and right heart failure. During the last decades, an improved understanding of the pathophysiology of the disease has resulted in the development of effective therapies targeting endothelial dysfunction (epoprostenol and derivatives, endothelin receptor antagonists and phosphodiesterase type 5 inhibitors). These drugs allow clinical, functional and hemodynamic improvement. Even though, no cure exists for PAH and prognosis remains poor. Recently, several additional pathways have been suggested to be involved in the pathogenesis of PAH, and may represent innovative therapies. In this summary, we review conventional therapy, pharmacological agents currently available for the treatment of PAH and the benefit/risk ratio of potential future therapies.     

N-acetylglucosaminidase,myeloperoxidase and vascular endothelial growth factor serum levels in breast cancer patients

Inflammatory cells surround breast carcinomas and may act promoting tumor development or stimulating anti-tumor immunity. N-acetylglucosaminidase (NAG) has been employed to detect macrophage accumulation/activation. Myeloperoxidase (MPO) is considered a marker for neutrophils activity/accumulation. Vascular Endothelial Growth Factor (VEGF) is as strong pro-angiogenic cytokine. The aim of this study was to measure the systemic inflammatory response by measuring serum levels of NAG, MPO and VEGF in women diagnosed with breast cancer and associate this response to the peritumoral inflammatory infiltrate and to prognostic factors. Serum samples obtained from women with no evidence of disease (n = 31) and with breast cancer (n = 68) were analyzed for the activities of NAG, MPO and VEGF by enzymatic assay. Serum levels of NAG and VEGF were higher in healthy volunteers (P < 0.0001) and serum levels of MPO were higher in patients with breast cancer (P = 0.002). Serum levels of NAG were positively correlated to serum levels of MPO and VEGF (P < 0.0001 and P = 0.0012, respectively) and MPO and VEGF serum levels had also a positive correlation (P = 0.0018). The inflammatory infiltrate was not associated to serum levels of the inflammatory markers, and higher levels of MPO were associated to lymphovascular invasion negativity (P = 0.0175).     

Transplantation of CD34+ cells for myocardial ischemia

CD34+ cells are multipotent hematopoietic stem cells also known as endothelial progenitor cells and are useful in regenerative medicine. Naturally, these cells are mobilized from the bone marrow into peripheral circulation in response to ischemic tissue injury. CD34+ cells are known for their high proliferative and differentiation capacities that play a crucial role in the repair process of myocardial damage. They have an important paracrine activity in secreting factors to stimulate vasculogenesis, reduce endothelial cells and cardiomyocytes apoptosis, remodel extracellular matrix and activate additional progenitor cells. Once they migrate to the target site, they enhance angiogenesis, neovascularization and tissue regeneration. Several trials have demonstrated the safety and efficacy of CD34+ cell therapy in different settings, such as peripheral limb ischemia, stroke and cardiovascular disease. Herein, we review the potential utility of CD34+ cell transplantation in acute myocardial infarction, refractory angina and ischemic heart failure.     

Caveolin-1与血管新生相关性的研究进展

缺血性中风是严重危害人类健康的疾病之一,对其防治与机制研究一直是当今医学界研究的热点之一。目前,无论是超早期溶栓治疗,还是营养脑细胞等对症治疗,都是着眼于挽救濒死的神经元,减少神经元死亡,保护神经功能。血管新生是缺血区组织抗损伤和神经元修复的结构基础,缺血性脑血管病治疗后血管新生可以促进中枢神经的再生。脑缺血后许多分子相互和谐的作用有助于脑缺血后的血管新生。研究证实,细胞膜微囊蛋白-1（Caveolin-1）在血管新生中扮演了关键的角色。该文对Caveolin-1与血管新生相关性的研究进展进行简要的综述。     

Interleukin 10 knockout frail mice develop cardiac and vascular dysfunction with increased age

Cardiovascular dysfunction is a primary independent predictor of age-related morbidity and mortality. Frailty is associated with activation of inflammatory pathways and fatigue that commonly presents and progresses with age. Interleukin 10 (IL-10), the cytokine synthesis inhibitory factor, is an anti-inflammatory cytokine produced by immune and non-immune cells. Homozygous deletion of IL-10 in mice yields a phenotype that is consistent with human frailty, including age-related increases in serum inflammatory mediators, muscular weakness, higher levels of IGF-1 at midlife, and early mortality. While emerging evidence suggests a role for IL-10 in vascular protection, a clear mechanism has not yet been elucidated.     

基于肠道菌群探讨运动改善2型糖尿病小鼠骨髓内皮组细胞功能的影响研究

目的：探讨有氧联合抗阻运动是否通过改善肠道有益菌群的多样性、丰度、结构及其对2型糖尿病小鼠骨髓内皮祖细胞（endothelial progenitor cells,EPCs）功能的影响。方法：将40只8周龄雄性db/db小鼠随机分为空白对照组（DZ组）糖尿病模型+有氧联合抗阻运动组（联合运动）（L组）、糖尿病模型+粪便移植组（SY组）、糖尿病模型组（TJ组）,每组10只。L组进行8周有氧联合抗阻运动干预,于周一、周三和周五进行有氧运动,周二、周四和周六进行抗阻运动,6 d/周。SY组和TJ组分别采用L组运动8周后的小鼠粪便和DZ组小鼠粪便制成悬浊液予灌肠,2次/d,共14 d。灌肠结束后检测各组小鼠骨髓EPCs增殖、迁移、黏附和体外血管生成能力,采用流式细胞仪检测鉴定EPCs表型CD34和CD31,16SrRNA检测各组小鼠粪便肠道菌群的丰度及多样性ELISA检测各组小鼠血清胰高血糖素样肽-1(glucagon-like peptide1,GLP-1)。结果：肠道菌群多样性结果显示,在纲水平上,与TJ组比较,SY组小鼠肠道Clostridia(54.60%vs. 32.21%)和Bac...