他汀类药物对缺血性脑卒中的预防作用

目的 探析他汀类药物预防缺血性脑卒中的作用.方法 对高血压、血脂异常动脉粥样硬化、糖尿病等缺血性脑卒中的危险因素分类进行探讨.结果 他汀类药物在缺血性脑卒中一级预防和二级预防中可降低其发生率的20%～34%.结论 近年来多个临床研究显示,他汀类调脂药物可有效降低缺血性脑卒中的发生率.     

他汀类药物对细胞因子及颈内动脉内膜的影响研究进展

他汀类药物在降脂的同时,还具有非调脂作用,如抑制血管炎症、稳定斑块、预防血栓形成、增加NO以改善内皮功能,这些可明显降低缺血性脑卒中的发生。脑动脉硬化是缺血性脑卒中的主要原因之一,动脉粥样硬化是由炎症反应介导的一个脂质沉积于动脉壁形成局部斑块的过程,其中细胞间黏附分子-1、巨噬细胞集落刺激因子、氧化修饰低密度脂蛋白在粥样硬化的形成和进展及加重过程中起着重要作用,本文就他汀类药物对动脉粥样硬化形成过程中炎症反应的细胞间黏附分子-1、巨噬细胞集落刺激因子、氧化修饰低密度脂蛋白及颈内动脉内膜的影响进行综述。     

RBP4 和omentin-1 与颈动脉狭窄缺血性脑卒中的关系

目的探讨血清中视黄醇结合蛋白4（RBP4）和网膜素-1（omentin-1）与颈动脉狭窄缺血性脑卒中的关系。方法选取50 例对照人群,143 例颈动脉狭窄缺血性脑卒中患者。缺血性脑卒中患者根据超声多普勒分为轻度狭窄组（颈动脉正常或狭窄＜50%,67 例）、中度狭窄组（颈动脉狭窄50%～70%,45 例）和重度狭窄组（颈动脉狭窄>70%至接近闭塞,31 例）。自动生化分析仪检测各组体质指数（BMI）、高血压情况、总胆固醇（TC）、三酰甘油（TG）、高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）和空腹血糖（FPG）,用ELISA 法检测各组血清中RBP4 和omentin-1 的含量,分析颈动脉狭窄缺血性脑卒中的危险因素。结果中、重度颈动脉狭窄组合并高血压比例明显多于对照组及轻度狭窄组（P＜0.05）,血清TC、TG、LDL-C、FPG 和RBP4 水平明显高于对照组（P＜ 0.05）,而omentin-1 水平明显低于对照组（P＜0.05）。Logistic 回归显示高TC、RBP4 是颈动脉狭窄缺血性脑卒中的危险因素,而高omentin-1 是保护因素。结论脂肪因子RBP4 是发生颈动脉狭窄缺血性脑卒中的危险因素而 omentin-1 是保护因素。     

瑞舒伐他汀强化降脂对缺血性脑卒中血脂及颈动脉粥样硬化斑块的影响

目的分析研究瑞舒伐他汀强化降脂对缺血性脑卒中血脂(TC)及颈动脉粥样硬化斑块(IMT)的影响。方法 50例缺血性脑卒中患者作为研究对象,随机分为对照组和观察组,各25例。对照组给予瑞舒伐他汀片10 mg/次,1次/d;观察组给予瑞舒伐他汀片20 mg/次,1次/d,持续治疗6个月,比较两组治疗前后血脂水平及颈动脉粥样硬化斑块的变化。结果观察组和对照组治疗后的血脂水平及颈动脉粥样硬化斑块较治疗前均有明显减退,两组治疗前血脂水平及颈动脉粥样硬化斑块情况比较,差异无统计学意义(P>0.05),两组治疗后的血脂水平及颈动脉粥样硬化斑块变化差异有统计学意义(P<0.05)。结论瑞舒伐他汀强化降脂治疗缺血性脑卒中的疗效显著,既可以起到良好的调脂作用,也可降低颈动脉粥样硬化颈动脉内膜-中层厚度(CMT),缓解了颈动脉粥样硬化斑块的进展。     

微白蛋白尿与缺血性脑卒中

缺血性脑卒中(CVD),占所有脑卒中的87％.动脉粥样硬化、高血压、糖尿病、血脂异常、吸烟、房颤等是缺血性脑卒中的重要危险因素.近年来,越来越多的因素被发现与缺血性脑卒中有关,微白蛋白尿是其中的一个.临床研究显示,微白蛋白尿与心血管疾病、脑血管疾病、周围血管疾病、动脉粥样硬化都有密切的联系[1].     

西洛他唑的药理作用和在缺血性脑卒中中的应用

目的:为临床合理使用西洛他唑提供参考。方法:对国、内外有关西洛他唑治疗缺血性脑卒中的研究文献进行综述。结果:西洛他唑可通过抗血小板聚集、抗动脉粥样硬化、促进血管内皮恢复、抑制细胞凋亡等多种机制发挥脑保护作用,对缺血性脑卒中的预防和治疗具有实用性价值。结论:西洛他唑既可以作为治疗缺血性脑卒中的药物,也可以作为缺血性脑卒中复发的预防药物。     

脑卒中高风险人群中颈动脉斑块形成的危险因素分析

<正>颈动脉粥样硬化被认为是导致缺血性脑卒中的重要因素之一。颈动脉斑块(CP)是早期颈动脉动脉粥样硬化的亚临床标志~([1]),并且可以预测缺血性脑卒中的发生~([2])。以往的研究发现,颈总动脉硬度增加与缺血性脑卒中有关~([3])。此外,研究发现,静息     

急性脑梗死患者血清C-反应蛋白含量观察及分析

脑梗死(cerebral infarction)又称缺血性脑卒中(cerebralischemic stroke),是临床常见病之一,而急性脑梗死是脑梗死中发病最多且危险性最高的一类.急性脑梗死多在动脉粥样硬化基础上发生,而动脉粥样硬化则是一个慢性炎症过程,其中缺血后一系列炎症级联反应可能是导致进一步脑损伤的主要因素之一[1].本文报道急性缺血性脑卒中患者血清C-反应蛋白( C-reactive protein,CRP)水平变化及探讨其临床意义.报告如下.     

青年缺血性脑卒中的脑血管特征及病因分析

目的:分析青年缺血性脑卒中患者的脑血管造影结果及CISS病因分型,探讨青年缺血性脑卒中的脑血管特征及发病原因。方法:总结2002年1月至2012年12月期间,在大连医科大学附属二院神经内科行脑血管造影检查的青年缺血性脑卒中患者38例,回顾性分析患者DSA资料及CISS分型。结果:1.38例青年缺血性脑卒中患者中,男性29例,女性9例。2.脑血管造影检查结果示:38例患者中颅内外动脉狭窄27例,动脉瘤3例,Moyamoya病2例,脑血管畸形1例,未见异常者5例;单纯前循环受累最多,为20例。3.38例患者中存在动脉狭窄病变的血管共有55支,其中大脑中动脉最多,为18支。5.38例患者中,包括大动脉粥样硬化20例,穿支动脉疾病4例,其他病因8例,病因不确定6例。结论:1.青年缺血性脑卒中患者以男性为主。2.青年缺血性脑卒中血管病变以动脉狭窄为主,其中单纯前循环受累最常见。3.大脑中动脉是青年缺血性脑卒中患者动脉狭窄的好发部位。4.青年缺血性脑卒中CISS分型以大动脉粥样硬化型为主。     

血清网膜素、脂联素在丙型肝炎肝硬化患者的临床意义

目的 测定丙型肝炎肝硬化患者血清网膜素、脂联素水平,探讨其与胰岛素、Child-Pugh分级及肝脏生化指标及血脂间的关系.方法 测定56例丙型肝炎肝硬化(A级17例,B级20例,C级19例)患者和32例健康对照的血清网膜素、脂联素及相关的临床生化参数.结果 肝硬化患者血清网膜素、脂联素水平明显高于正常对照组(P<0唵.05),肝硬化组内A、B、C三级间网膜素、脂联素水平差异无统计学意义(P>0.05),肝硬化组患者血清网膜素、脂联素水平与HOMA-IR、胰岛素水平无明显相关性(r值分别为-0.07、-0.14、-0.10、-0.04,P>0.05),网膜素水平与脂联素呈正相关(r=0.37,P<0.01).结论 丙型肝炎肝硬化时网膜素、脂联素升高,可作为预测丙型肝炎肝硬化的指标,但不能作为肝功能严重程度的指标.     

Emodin inhibits LPS-induced inflammatory response by activating PPAR-γ in mouse mammary epithelial cells

Emodin, an anthraquinone derivative isolated from the rhizomes of Rheum palmatum, has been reported to have a protective effect against lipopolysaccharide (LPS)-induced mastitis. However, the underlying molecular mechanisms are not well understood. The aim of this study was to investigate the molecular mechanisms of emodin in modifying lipopolysaccharide (LPS)-induced signaling pathways in mouse mammary epithelial cells (MEC). The pro-inflammatory cytokines were determined by ELISA. Nuclear factor-κB (NF-κB), inhibitory kappa B (IκBα) protein, p38, extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and PPAR-γ were determined by Western blotting. The results showed that emodin suppressed tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), iNOS and COX-2 expression. We also found that emodin inhibited LPS-induced NF-κB activation, IκBα degradation, phosphorylation of ERK, JNK and P38. Furthermore, emodin could activate PPAR-γ and the anti-inflammatory effects of emodin can be reversed by GW9662, a specific antagonist for PPAR-γ. In conclusion, our results demonstrate that emodin activates PPAR-γ, thereby attenuating LPS-induced inflammatory response.     

PPAR-γ agonist pioglitazone regulates dendritic cells immunogenicity mediated by DC-SIGN via the MAPK and NF-κB pathways

Dendritic cell-specific ICAM-3 grabbing non-integrin (DC-SIGN) is a dendritic cell-specific lectin which participates in dendritic cell (DC) trafficking, antigen uptake and DC–T cell interactions at the initiation of immune responses. This study investigated whether peroxisome proliferator-activated receptor-gamma (PPAR-γ) activation in human DCs regulates the immunogenicity of DCs mediated by DC-SIGN and exploited the possible molecular mechanisms, especially focused on the signaling pathways of mitogen-activated protein kinases (MAPK) and nuclear factor-κB (NF-κB). Here, we show that the PPAR-γ agonist pioglitazone decreased DC adhesion and transmigration, and DC stimulation of T cell proliferation mediated by DC-SIGN dependent on activation of PPAR-γ, although it increased DC endocytosis independent of PPAR-γ activation. Furthermore, PPAR-γ activation by pioglitazone in DCs down-regulated the expression of DC-SIGN, which was mediated by modulating the balance of the signaling pathways of extracellular signal-regulated kinase, c-Jun N-terminal kinase and NF-κB, but not p38 MAPK. Therefore, we conclude that PPAR-γ activation in human DCs regulates the immunogenicity of DCs mediated by DC-SIGN via the pathways of MAPK and NF-κB. These findings may support the important role of these mediators in the regulation of DC-mediated inflammatory and immunologic processes.     

Ellagic acid protects endothelial cells from oxidized low-density lipoprotein-induced apoptosis by modulating the PI3K/Akt/eNOS pathway

Endothelial apoptosis is a driving force in atherosclerosis development. Oxidized low-density lipoprotein (oxLDL) promotes inflammatory and thrombotic processes and is highly atherogenic, as it stimulates macrophage cholesterol accumulation and foam cell formation. Previous studies have shown that the phosphatidylinositol 3-kinase/Akt/endothelial nitric oxide synthase/nitric oxide (PI3K/Akt/eNOS/NO) pathway is involved in oxLDL-induced endothelial apoptosis. Ellagic acid, a natural polyphenol found in berries and nuts, has in recent years been the subject of intense research within the fields of cancer and inflammation. However, its protective effects against oxLDL-induced injury in vascular endothelial cells have not been clarified. In the present study, we investigated the anti-apoptotic effect of ellagic acid in human umbilical vein endothelial cells (HUVECs) exposed to oxLDL and explored the possible mechanisms. Our results showed that pretreatment with ellagic acid (5-20 μM) significantly attenuated oxLDL-induced cytotoxicity, apoptotic features, and generation of reactive oxygen species (ROS). In addition, the anti-apoptotic effect of ellagic acid was partially inhibited by a PI3K inhibitor (wortmannin) and a specific eNOS inhibitor (cavtratin) but not by an ERK inhibitor (PD98059). In exploring the underlying mechanisms of ellagic acid action, we found that oxLDL decreased Akt and eNOS phosphorylation, which in turn activated NF-κB and downstream pro-apoptotic signaling events including calcium accumulation, destabilization of mitochondrial permeability, and disruption of the balance between pro- and anti-apoptotic Bcl-2 proteins. Those alterations induced by oxLDL, however, were attenuated by pretreatment with ellagic acid. The inhibition of oxLDL-induced endothelial apoptosis by ellagic acid is due at least in part to its anti-oxidant activity and its ability to modulate the PI3K/Akt/eNOS signaling pathway.     

Sauchinone suppresses lipopolysaccharide-induced inflammatory responses through Akt signaling in BV2 cells

Activated microglial cells play an important role in inflammatory responses in the central nervous system (CNS) that are involved in neurodegenerative diseases. Sauchinone has been shown to modulate the expression of inflammatory factors through nuclear factor-kappa B (NF-κB) signaling pathway. Here, we examined the effect of sauchinone on the inflammatory responses of microglia cells induced by lipopolysaccharide (LPS) and explored the mechanism underlying action of sauchinone. BV2 cells treated with LPS showed an up-regulation of nitric oxide (NO) and prostaglandin (PGE(2)) release, whereas sauchinone suppressed this up-regulation. Sauchinone inhibited both mRNA and protein expression of COX-2, iNOS, TNF-α and IL-1β. In addition, sauchinone blocked the activation of NF-κB through its inhibition of I-κB phosphorylation. Interestingly, sauchinone had no effect on the LPS-induced phosphorylation of mitogen activated protein kinases (MAP kinases; ERK1/2, p38, JNK), but it did inhibit Akt phosphorylation. These results suggest that the inhibitory effect of sauchinone on the LPS-induced production of inflammatory mediator in BV2 cells is associated with the suppression of the NF-κB and Akt signaling pathways. Therefore, sauchinone may be a useful treatment for neurodegenerative disease by inhibiting inflammatory responses in activated microglia.     

The molecular basis for the pharmacological activity of anthocyans

This review summarizes the current knowledge of the regulatory role of pure anthocyans in cellular signaling pathways and gene expression. The molecular basis for anthocyans pharmacological activity includes the regulation of plethora of mechanisms mainly involved in: (1) suppression of the inflammatory response through targeting the phospholipase A2 and PI3K/Akt and NF-κB pathways, (2) protection from cardiovascular disease by exerting (i) antihypertensive and endothelium-protective activity through targeting the Akt/eNOS and ACE pathways (ii) antiatherogenic activity through targeting NF-κB mediated VCAM and ICAM expression, (3) growth/differentiation control and tumor suppression by exerting (i) anticancerogenic activity through targeting the EGF and HGF signaling pathways (ii) tumor anti-invasive activity through targeting the VEGF signaling pathway and ECM degrading enzymes (iii) cell cycle arrest and induction of apoptosis through the JNK/p38 MAPK mediated caspase activation (iv) modulation of chemotherapeutic efficacy by affecting resistance to anticancer drugs, (4) reduction of diabetes incidence through modulation of insulin sensitivity and glucose utilization, (5) neuroprotection through amelioration of oxidative stress and Aβ deposition, and (6) hepatoprotective activity through interference with TNF-α and TGF-β in the liver. The estrogen-like activity of anthocyans could be utilized in cancer and hormone-replacement therapy. These data provide a concise insight into molecular mechanisms of protective and therapeutic activity of anthocyans in various pathological conditions, which may not be attributed solely to their antioxidant activity but also to direct blockage of signaling pathways. Structure-activity analysis reveals that the number of hydroxyl groups and presence of sugar moiety are crucial for their specific modulatory actions.     

Lack of glutathione peroxidase-1 facilitates a pro-inflammatory and activated vascular endothelium

A critical early event in the pathogenesis of atherosclerosis is vascular inflammation leading to endothelial dysfunction (ED). Reactive oxygen species and inflammation are inextricably linked and declining antioxidant defense is implicated in ED. We have previously shown that Glutathione peroxidase-1 (GPx1) is a crucial antioxidant enzyme in the protection against diabetes-associated atherosclerosis. In this study we aimed to investigate mechanisms by which lack of GPx1 affects pro-inflammatory mediators in primary aortic endothelial cells (PAECs) isolated from GPx1 knockout (GPx1 KO) mice. Herein, we demonstrate that lack of GPx1 prolonged TNF-α induced phosphorylation of P38, ERK and JNK, all of which was reversed upon treatment with the GPx1 mimetic, ebselen. In addition, Akt phosphorylation was reduced in GPx1 KO PAECs, which correlated with decreased nitric oxide (NO) bioavailability as compared to WT PAECs. Furthermore, IκB degradation was prolonged in GPx1 KO PAECS suggesting an augmentation of NF-κB activity. In addition, the expression of vascular cell adhesion molecule (VCAM-1) was significantly increased in GPx1 KO PAECs and aortas. Static and dynamic flow adhesion assays showed significantly increased adhesion of fluorescently labeled leukocytes to GPx1 KO PAECS and aortas respectively, which were significantly reduced by ebselen treatment. Our results suggest that GPx1 plays a critical role in regulating pro-inflammatory pathways, including MAPK and NF-κB, and down-stream mediators such as VCAM-1, in vascular endothelial cells. Lack of GPx1, via effects on p-AKT also affects signaling to eNOS-derived NO. We speculate based on these results that declining antioxidant defenses as seen in cardiovascular diseases, by failing to regulate these pro-inflammatory pathways, facilitates an inflammatory and activated endothelium leading to ED and atherogenesis.     

Rutin inhibits B[a]PDE-induced cyclooxygenase-2 expression by targeting EGFR kinase activity

Rutin is a well-known flavonoid that exists in various natural sources. Accumulative studies have represented the biological effects of rutin, such as anti-oxidative and anti-inflammatory effects. However, the underlying mechanisms of rutin and its direct targets are not understood. We investigated whether rutin reduced B[a]PDE-induced-COX-2 expression. The transactivation of AP-1 and NF-κB were inhibited by rutin. Rutin also attenuated B[a]PDE-induced Raf/MEK/ERK and Akt activation, but had no effect on the phosphorylation of EGFR. An in vitro kinase assay revealed rutin suppressed EGFR kinase activity. We also confirmed direct binding between rutin and EGFR, and found that the binding was regressed by ATP. The EGFR inhibitor also inhibited the B[a]PDE-induced MEK/ERK and Akt signaling pathways and subsequently, suppressed COX-2 expression and promoter activity, in addition to suppressing the transactivation of AP-1 and NF-κB. In EGFR^–/–mouse embryonic fibroblast cells, B[a]PDE-induced COX-2 expression was also diminished. Collectively, rutin inhibits B[a]PDE-induced COX-2 expression by suppressing the Raf/MEK/ERK and Akt signaling pathways. EGFR appeared to be the direct target of rutin.     

Coactivation of the PI3K/Akt and ERK signaling pathways in PCB153-induced NF-κB activation and caspase inhibition

Polychlorinated biphenyls (PCBs) are a group of persistent and widely distributed environmental pollutants that have various deleterious effects, e.g., neurotoxicity, endocrine disruption and reproductive abnormalities. In order to verify the hypothesis that the PI3K/Akt and MAPK pathways play important roles in hepatotoxicity induced by PCBs, Sprague–Dawley (SD) rats were dosed with PCB153 intraperitoneally at 0, 4, 16 and 32 mg/kg for five consecutive days; BRL cells (rat liver cell line) were treated with PCB153 (0, 1, 5, and 10 μM) for 24 h. Results indicated that the PI3K/Akt and ERK pathways were activated in vivo and in vitro after exposure to PCB153, and protein levels of phospho-Akt and phospho-ERK were significantly increased. Nuclear factor-κB (NF-κB) activation and caspase-3, -8 and -9 inhibition caused by PCB153 were also observed. Inhibiting the ERK pathway significantly attenuated PCB153-induced NF-κB activation, whereas inhibiting the PI3K/Akt pathway hardly influenced phospho-NF-κB level. However, inhibiting the PI3K/Akt pathway significantly elevated caspase-3, -8 and -9 activities, while the ERK pathway only synergistically regulated caspase-9. Proliferating cell nuclear antigen (PCNA), a reliable indicator of cell proliferation, was also induced. Moreover, PCB153 led to hepatocellular hypertrophy and elevated liver weight. Taken together, PCB153 leads to aberrant proliferation and apoptosis of hepatocytes through NF-κB activation and caspase inhibition, and coactivated PI3K/Akt and ERK pathways play critical roles in PCB153-induced hepatotoxicity.