剪切力增高对大鼠腹主动脉管径及管壁MMP-9表达的影响

目的:观察腹主动脉局部剪切力增高对其管径及管壁MMP-9表达的影响,分析剪切力增高在动脉重塑中的作用。方法:SD大鼠48只，随机分8组，实验组和对照组各4 组。实验组行肾动脉下腹主动脉-下腔静脉细针穿刺造瘘，术后1，7，14，28 d取标本，观察动脉管径及管壁结构的变化。对照组除不造瘘外，操作同实验组。结果:实验组术后1 d，瘘口近端动脉管径明显增大（P＜0.05),管壁变薄（P＜0.05)，随时间的延长，管径不断增大，管壁不断变薄。MMP-9于术后1 d开始表达，术后7d达高峰（P＜0.01）,并持续高表达(P＜0.01)。结论:剪切力增高可使大鼠腹主动脉出现管径增大，管壁变薄的正性重塑，并导致管壁MMP-9表达上调；此正性重塑与MMP-9表达密切关联；剪切力增高，MMP-9表达增多是导致动静脉瘘形成后瘘口近远端逐渐膨大的重要因素。     

牵拉应力在5-氮杂胞苷诱导骨髓间充质干细胞成肌过程中的动态效应

背景:国内外研究发现在一定力学环境下,体外培养的间充质干细胞其增殖分化等一系列生物学特性会发生相应变化.目的:体外观察5-氮杂胞苷与牵拉应力对大鼠骨髓间充质干细胞向肌细胞分化的调控作用.设计、时间及地点:2006-01/2007-06在上海交通大学牛物力学实验室完成的细胞观察实验.材料:清洁级3-4周龄雄性SD大鼠30只用于分离培养骨髓间充质干细胞,1～3d龄SD新生鼠4只用于建立骨骼肌阳性细胞株.化学诱导剂5-氮杂胞苷为Sigma公司产品,牵拉设备Fx-4000 Flexercell由美国Flexcell Int公司生产.方法:将传至第4代的骨髓间充质干细胞接种于Flex 6孔板.[1]设立5组行成肌家族因子表达Western-Blot检测:第1组细胞单纯经10μmol/L 5-氮杂胞苷诱导1周;第2～4组细胞以10μmol/L 5-氮杂胞苷诱导1周后,在1Hz频率、15%幅度应力条件下分别牵拉12,24,36h;第5组以新生鼠骨骼肌细胞作为阳性对照.[2]设立5组行诱导剂及牵拉应力作用的RT-PCR检测:第1组细胞给予1Hz频率、15%幅度应力牵拉24h;第2、3组分别经10μmol/L 5-氮杂胞苷诱导1,2周;第4组细胞经10μmol/L 5-氮杂胞苷诱导2周后,给与同等应力牵拉24h;第5组以新生鼠骨骼肌细胞作为阳性对照.主要观察指标:不同诱导条件及应力牵拉状态下骨髓间充质干细胞成肌家族因子的表达.结果:[1]第1组表达成肌因子MyoD与Myf5,成熟肌细胞标志MHC表达不显著;第2～4组MyoD与Myf5的表达明显增强(P<0.05),且随牵拉时间延长因子的表达逐步增强,MHC表达不显著.[2]第1组不表达成肌家族因子;第2组表达MyoD、 Myf5,第3组表达MyoD、 Myf5、 desmin,第4组几乎表达所有检測的肌细胞特异性标记.结论:经5-氮杂胞苷诱导可启动骨髓间充质干细胞向肌细胞分化,单独的牵拉应力不能诱导成肌.牵拉应力可调控5-氮杂胞苷对骨髓间充质干细胞的诱导分化进程,并且与牵拉作用时间成正性相关.     

Uncoupling protein 2 in the glial response to stress:implications for neuroprotection

Reactive oxygen species (ROS) are free radicals thought to mediate the neurotoxic effects of several neu-rodegenerative disorders. In the central nervous system, ROS can also trigger a phenotypic switch in both astrocytes and microglia that further aggravates neurodegeneration, termed reactive gliosis. Negative regulators of ROS, such as mitochondrial uncoupling protein 2 (UCP2) are neuroprotective factors that decrease neuron loss in models of stroke, epilepsy, and parkinsonism. However, it is unclear whether UCP2 acts purely to prevent ROS production, or also to prevent gliosis. In this review article, we discuss published evidence supporting the hypothesis that UCP2 is a neuroprotective factor both through its direct effects in decreasing mitochondrial ROS and through its effects in astrocytes and microglia. A major effect of UCP2 activation in glia is a change in the spectrum of secreted cytokines towards a more anti-inlfammatory spec-trum. There are multiple mechanisms that can control the level or activity of UCP2, including a variety of metabolites and microRNAs. Understanding these mechanisms will be key to exploitingthe protective effects of UCP2 in therapies for multiple neurodegenerative conditions.     

Axon injury induced endoplasmic reticulum stress and neurodegeneration

Injury to central nervous system axons is a common early characteristic of neurodegenerative diseases. Depending on its location and the type of neuron, axon injury often leads to axon degeneration, retrograde neuronal cell death and progressive permanent loss of vital neuronal functions. Although these sequential events are clearly connected, ample evidence indicates that neuronal soma and axon degenerations are active autonomous processes with distinct molecular mechanisms. By exploiting the anatomical and technical advantages of the retinal ganglion cell(RGC)/optic nerve(ON) system, we demonstrated that inhibition of the PERK-e IF2α-CHOP pathway and activation of the X-box binding protein 1 pathway synergistically protect RGC soma and axon, and preserve visual function, in both acute ON traumatic injury and chronic glaucomatous neuropathy. The autonomous endoplasmic reticulum(ER) stress pathway in neurons has been implicated in several other neurodegenerative diseases. In addition to the emerging role of ER morphology in axon maintenance, we propose that ER stress is a common upstream signal for disturbances in axon integrity, and that it leads to a retrograde signal that can subsequently induce neuronal soma death. Therefore manipulation of the ER stress pathway may be a key step toward developing the effective neuroprotectants that are greatly needed in the clinic.     

一氧化氮合酶、氧化应激与糖尿病心肌病

<正>心血管疾病是糖尿病患者最普遍的发病率和致死率的病因。高血糖不仅引起血管损害,同时也直接损害心肌细胞。已经证明糖尿病心肌病导致缺血性事件的死亡率增加。活性     

Gum resin extract of Boswellia serrata attenuates lipopolysaccharide-induced inflammation and oxidative damage in hepatic and renal tissues of rats

Objective:To explore the effect of ethyl acetate gum resin extract of Boswellia serrata on lipopolysaccharide(LPS)induced inflammation and oxidative damage in hepatic and renal tissues of rats.Methods:The rats were divided into four groups:control,LPS,LPS+Boswellia serrata extracts(100 mg/kg and 200 mg/kg).LPS(1 mg/kg)and the extract(100 and 200 mg/kg,30 min before LPS)were administered intraperitoneally for 3 weeks.The levels of liver enzymes,albumin,total protein,creatinine,blood urea nitrogen(BUN),interleukin(IL)-6,malondialdehyde(MDA),and total thiol groups and superoxide dismutase(SOD)and catalase(CAT)activities were measured.Results:The levels of liver enzymes,creatinine,and BUN,IL-6,MDA in the LPS group were markedly increased(P<0.001)while albumin,total protein,and total thiol concentration,as well as SOD and CAT activities,were decreased compared with the control group(P<0.05 or 0.01).Boswellia serrata extracts diminished the levels of liver enzymes,creatinine,BUN,IL-6,and MDA(P<0.01 and P<0.001),and elevated the concentration of total protein and total thiol and SOD and CAT activities(P<0.05 or 0.01).Conclusions:The ethyl acetate gum resin extract of Boswellia serrata reduces LPS-induced inflammatory reactions and oxidative damage,thus ameliorating hepatic and renal function.     

Malondialdehyde levels in diabetic retinopathy patients: a systematic review and meta-analysis

Background: It remains unclear whether circulating malondialdehyde (MDA) levels change in people with diabetic retinopathy (DR). This systematic review compared circulating MDA levels in diabetic people with and without DR.Methods: PubMed, Medline (Ovid), Embase (Ovid), and Web of Science were searched for case-control studies conducted before May 2022 in English that compared circulating MDA levels in people with and without DR. The following MeSH search terms were used: ( malondialdehyde or ...     

Nuclear factor-Y mediates pancreatic β-cell compensation by repressing reactive oxygen species-induced apoptosis under metabolic stress

Background: Pancreatic β-cells elevate insulin production and secretion through a compensatory mechanism to override insulin resistance under metabolic stress conditions. Deficits in β-cell compensatory capacity result in hyperglycemia and type 2 diabetes (T2D). However, the mechanism in the regulation of β-cell compensative capacity remains elusive. Nuclear factor-Y (NF-Y) is critical for pancreatic islets’ homeostasis under physiological conditions, but its role in β-cell compensatory response...     

Blockade of c-Src Within the Paraventricular Nucleus Attenuates Inflammatory Cytokines and Oxidative Stress in the Mechanism of the TLR4 Signal Pathway in Salt-Induced Hypertension

Toll-like receptor 4 (TLR4) and cellular Src (cSrc) are closely associated with inflammatory cytokines and oxidative stress in hypertension, so we designed this study to explore the exact role of c-Src in the mechanism of action of the TLR4 signaling pathway in salt-induced hypertension. Salt-sensitive rats were given a high salt diet for 10 weeks to induce hypertension. This resulted in higher levels of TLR4, activated c-Src, pro-inflammatory cytokines, oxidative stress, and arterial pressure. Infusion of a TLR4 blocker into the hypothalamic paraventricular nucleus (PVN) decreased the activated c-Src, while microinjection of a c-Src inhibitor attenuated the PVN levels of nuclear factor-kappa B, pro-inflammatory cytokines, and oxidative stress. Our findings suggest that a longterm high-salt diet increases TLR4 expression in the PVN and this promotes the activation of c-Src, which upregulates the expression of pro-inflammatory cytokines and results in the overproduction of reactive oxygen species.Therefore, inhibiting central c-Src activity may be a new target for treating hypertension.