Usefulness of plasma oxidative biomarker in patients with acute cerebral infarction

1)我们评估了血浆生物标志物用于监测脑损伤和依达拉奉治疗效果的有效性。本研究包括51例缺血性脑梗塞患者。GI组24例为皮质损害，GII组27例为基底节或脑干损害。随机选择27例患者(GIA，n=13；GIIa，n=14)给予依达拉奉治疗，并与未服用依达拉奉的患者(GIB，n=11，GII，n=13)的血浆氧化低密度脂蛋白-1，S-100B-和锰超氧化物歧化酶水平进行比较，以研究依达拉奉的疗效。依达拉奉治疗3天后，GIA患者血浆氧化低密度脂蛋白水平显著低于GIB患者(0.177±0.024 ng/μg apoB比0.219±0.026，P<0.05)。GII患者治疗前后血浆氧化低密度脂蛋白差异无统计学意义(0.156±0.013比0.152±0.020)。GIA患者血清S-100B、MnSOD值明显低于GIB患者(P<0.05)。出院时GIA的神经状况已经恢复，但GIB Pati…还没有恢复更多的ENTS。我们的研究首次通过血浆生物标志物证实了依达拉奉的疗效。2)血管紧张素II(Ang II)AT1受体阻滞剂坎地沙坦(Candesartan)对高血压大鼠的脑缺血具有保护作用。为了阐明这种保护作用背后的血压非依赖性机制，我们在体内使用了正常血压的大鼠，在体外实验中使用了人脐静脉内皮细胞(HUVEC)。Wistar大鼠在给予ARB(0.5或1 mg/kg/d)预处理2周后，造成大脑中动脉(MCA)闭塞再灌注2小时。适当浓度的坎地沙坦与Ang II共同或不与Ang II共同刺激HUVEC。在ARB处理的正常血压大鼠，皮质梗死体积减小。这与氧化损伤和缺氧的减少、皮质半影区eNOS蛋白和大脑中动脉enos mRNA表达的增加有关。在HUVEC中，ARB和Ang II均增加eNOS蛋白的表达。Ang II增加细胞内ROS和NO的产生，导致eNOS解偶联形成超氧化物歧化。当ARB抑制这些增加时，在Ang II存在和不存在的情况下，它增加了细胞外NO的释放和血红素加氧酶-1的蛋白表达，提示ARB直接增强了NO的可获得性和抗氧化作用。我们的文献首次证明ARB可增强内皮功能和抗氧化防御系统，从而有助于保护皮质半影区免受脑缺血的影响。ARB通过血压和血管紧张素Ⅱ非依赖性机制改善缺血后内皮功能障碍，可能是预防脑缺血后果的一种治疗手段。较少

1) We assess the availability of plasma biomarkers to monitor the brain damage and the therapeutic efficacy of edaravone. The study consisted of 51 patients with ischemic cerebral infarcts. They were divided into 2 groups; GI (n=24) had cortical lesions, GII (n=27) had lesions in the basal ganglia or brain stem. Edaravone was administered to 27 randomly selected patients (GIa, n =13; GIIa, n =14) and its efficacy was studied by comparing their plasma OxLDL-, S-100B-, and MnSOD levels to those in patients without edaravone (GIb, n=11, GII, n=13). Three days after the start of edaravone, plasma OxLDL was significantly lower in GIa-than GIb patients (0.177±0.024 ng/μg apoB vs. 0.219±0.026, p<0.05). In GII patients, pre-and post-treatment plasma OxLDL was not significantly different (0.156±0.013 vs. 0.152±0.020). In GIa patients, S-100B and MnSOD were significantly lower than in GIb patients (p<0.05). The neurological condition at the time of discharge had recovered in GIa but not GIb pati … More ents. Ours is the first evidence to confirm the efficacy of edaravone by plasma biomarkers. In patients with cortical infarcts, edaravone reduced oxidative damage, thereby limiting the degree of brain damage.2) Candesartan, an angiotensin II (Ang II) AT1 receptor blocker (ARB), is protective against cerebral ischemia in hypertensive rats. To elucidate the blood pressure-independent mechanisms underlying this protection we used normotensive rats in our in vivo-and human umbilical endothelial cells (HUVEC) in our in vitro experiments. Wistar rats were subjected to 2-hr middle cerebral artery (MCA) occlusion-reperfusion after 2-week pretreatment with ARB (0.5 or 1 mg/kg/day). HUVEC were stimulated with an optimal concentration of candesartan with or without Ang II. In ARB-treated normotensive rats, the cortical infarct volume was decreased. This was associated with a decrease in oxidative damage and hypoxia, and an increase in the expression of eNOS protein in the cortical penumbra and of eNOS mRNA in the MCA. In HUVEC, both ARB and Ang II increased eNOS protein expression. Ang II increased intracellular ROS and NO production and led to eNOS "uncoupling" to form superoxide. While ARB inhibited these increases, it increased the extracellular NO release and the protein expression of heme oxygenase-1 in the absence and presence of Ang II, suggesting that ARB directly enhanced NO availability and anti-oxidative effects. Ours is the first documentation that ARB increases endothelial function and anti-oxidative defense system, thereby contributing to the protection of the cortical penumbra against cerebral ischemia. The improvement by ARB of post-ischemic endothelial dysfunction via blood pressure-and Ang II-independent mechanisms may represent a therapeutic means of protecting against the consequences of cerebral ischemia. Less