目的:评价白藜芦醇的神经保护作用,乌拉地尔,并联合应用上述药物对大鼠大脑中动脉阻塞(MCAO)诱导的缺血再灌注(IR)损伤模型。
方法:将35只大鼠分成5组,每组7只。IR中的动物,IR白藜芦醇(IRr),IR乌拉地尔(IRu),IR+白藜芦醇和乌拉地尔(IRc)联合暴露于MCAO致脑缺血再灌注损伤模型。IRr和IRu组大鼠分别接受30-mg/kg白藜芦醇和5-mg/kg乌拉地尔。IRc中的动物接受两种药物的联合治疗。在研究结束时,脑组织用于氧化应激(丙二醛,谷胱甘肽,和超氧化物歧化酶),促凋亡caspase-3,抗凋亡Bcl-2和促炎性肿瘤坏死因子-α细胞因子水平测量。
结果:MCAO模型成功复制了IR损伤,具有明显的组织病理学变化,升高的组织氧化应激,与对照组相比,IR组细胞凋亡和炎症蛋白表达上调(p<0.001)。与IR组相比,IRr组的所有参数均明显减轻(均p<0.05)。在IRu组中,除caspase-3和Bcl-2外,所有参数均与IR组差异显着(均p<0.05)。与IR组相比,IRc组在所有参数上显示出最大的差异(所有p<0.001)。IRc有较高的超氧化物歧化酶和Bcl-2水平,与IRr和IRu组相比,caspase-3水平较低(均p<0.05)。此外,与IRu组相比,IRc组的MDA和TNF-α水平较低(均p<0.05)。
结论:结果表明白藜芦醇和乌拉地尔联合治疗可能是下调脑IR损伤中神经变性的一种新策略。
OBJECTIVE: To evaluate the neuroprotective effect of resveratrol, urapidil, and a combined administration of these drugs against middle cerebral artery occlusion (MCAO) induced ischemia/reperfusion (IR) injury model in rats.
METHODS: Thirty-five rats were divided into five groups of seven animals each. Animals in IR, IR resveratrol (IRr), IR urapidil (IRu), and IR + combination of resveratrol and urapidil (IRc) were exposed to MCAO induced cerebral ischemia reperfusion injury model. Rats in IRr and IRu groups received 30-mg/kg resveratrol and 5-mg/kg urapidil respectively. Animals in IRc received a combined treatment of both drugs. At the end of the study, brain tissues were used for oxidative stress (malondialdehyde, glutathione, and superoxide dismutase), pro-apoptotic caspase-3, anti-apoptotic Bcl-2, and pro-inflammatory tumor necrosis factor-α cytokine level measurements.
RESULTS: The MCAO model successfully replicated IR injury with significant histopathological changes, elevated tissue oxidative stress, and upregulated apoptotic and inflammatory protein expression in IR group compared to control group (p < 0.001). All parameters were significantly alleviated in IRr group compared to IR group (all p < 0.05). In IRu group, all parameters except for caspase-3 and Bcl-2 were also significantly different than IR group (all p < 0.05). The IRc group showed the biggest difference compared to IR group in all parameters (all p < 0.001). The IRc had higher superoxide dismutase and Bcl-2 levels, and lower caspase-3 levels compared to both IRr and IRu groups (all p < 0.05). Also, the IRc group had lower MDA and TNF-α levels compared to IRu group (all p < 0.05).
CONCLUSIONS: The results indicate that combined treatment of resveratrol and urapidil may be a novel strategy to downregulate neurodegeneration in cerebral IR injury.