Usefulness of plasma oxidative biomarker in patients with acute cerebral infarction

1)评估血浆生物标志物监测脑损伤的可用性和依达拉奉的治疗效果。该研究包括51例缺血性脑梗死患者。他们被分为两组；GI （n=24）有皮质病变，GII （n=27）有基底神经节或脑干病变。随机选择27例患者（GIa组，n=13； GIIa组，n= 14）给予依达拉奉，通过与未服用依达拉奉的患者（GIb组，n=11， GII组，n=13）比较血浆OxLDL-、S-100B-、MnSOD水平，研究依达拉奉的疗效。依达拉奉治疗3 d后，gia组血浆OxLDL明显低于GIb组（0.177±0.024 ng/μg apoB vs. 0.219±0.026,p<0.05）。GII患者治疗前后血浆OxLDL差异无统计学意义（0.156±0.013∶0.152±0.020）。GIa患者S-100B、MnSOD水平明显低于GIb患者（p<0.05）。出院时，GIa患者的神经系统状况已经恢复，而GIb患者则没有。这是第一个通过血浆生物标志物证实依达拉奉疗效的证据。在皮质梗死患者中，依达拉奉可减少氧化损伤，从而限制脑损伤程度。2)坎地沙坦是血管紧张素II (Ang II) AT1受体阻滞剂（ARB），对高血压大鼠脑缺血具有保护作用。为了阐明这种保护的不依赖血压的机制，我们在体内和体外实验中分别使用了血压正常的大鼠和人脐带内皮细胞（HUVEC）。用ARB（0.5或1 mg/kg/天）预处理2周后，Wistar大鼠进行2小时大脑中动脉（MCA）闭塞再灌注。用坎地沙坦加或不加angii刺激HUVEC。arb治疗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以及皮层半暗带eNOS蛋白和MCA中eNOS mRNA表达的增加有关。在HUVEC中，ARB和Ang II都增加了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。虽然ARB抑制了这些增加，但在没有和存在Ang II的情况下，ARB增加了细胞外NO的释放和血红素加氧酶-1的蛋白表达，表明ARB直接增强了NO的可用性和抗氧化作用。我们的研究是第一个证明ARB增加内皮功能和抗氧化防御系统，从而有助于保护皮层半暗区免受脑缺血。ARB通过血压和不依赖于angii的机制改善缺血后内皮功能障碍，可能是一种预防脑缺血后果的治疗手段。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