Summary： The neuroproteetive effects of escitalopram oxalate in rats with chronic hypoperfusion and the possible mechanism were explored. Chronic hypoperfusion （2-VO） model was prepared and given escitalopram oxala...Summary： The neuroproteetive effects of escitalopram oxalate in rats with chronic hypoperfusion and the possible mechanism were explored. Chronic hypoperfusion （2-VO） model was prepared and given escitalopram oxalate （experimental group） or PBS （control group） after 6 weeks. Eight weeks after the operation, Morris water maze test was carried out to evaluate the learning and memory ability of the rats. The cell proliferation, three-dimensional vascular distribution, cell morphological changes in ischemic area and the plasma vascular endothelial growth factor （VEGF） were detected to explore the possible mechanisms. （1） Morris water maze test showed that the escape latency in the experimental group was significantly shorter than in the control group, while the first quadrant swimming time in the experi- mental group was significantly longer than the control group （both P〈0.01）. （2） Cerebrovascular confo- cal detection results showed that the inside diameter of capillaries was significantly less in the experi- mental group than in the control group; the vascular density was significantly increased in the experi- mental group and the total area of capillaries was also significantly increased in the experimental group as compared with the control group. （3） There was statistically significant difference in BrdU-positive cells in the ischemic brain tissue between the experimental group and the control group （P=0.003〈0.01）. （4） VEGF concentrations in the plasma and the ischemic area were higher in the experimental group than in the control group （P〈0.05）. It was concluded that escitalopram oxalate could significantly im- prove the learning and memory ability of the rats with chronic cerebral ischemia probably by the VEGF-mediated angiogenesis.展开更多
文摘目的 通过观察Klotho基因过表达对肾脏血管内皮生长因子(vascular endothelial growth factor,VEGF)的影响,进一步探讨Klotho基因对小鼠急性肾损伤(acute kidney injury,AKI)的保护作用机制。方法 构建可稳定高效表达Klotho基因的慢病毒载体,通过病毒转染骨髓间充质干细胞(bone marrow mesenchymal stem cells,BMSCs)技术获得高表达Klotho基因的BMSCs(overexpression of Klotho gene in BMSCs,BMSCs-Klotho)和对照空载体BMSCs(expression of empty vector in BMSCs,BMSCs-EV)。采用小鼠双侧股肌内注射50%甘油(8 ml/kg)导致横纹肌溶解的方法建立AKI模型。30只雄性C57BL/6小鼠随机分为5组,每组6只:正常对照(control,CON)组、PBS干预(AKI with PBS intervention,AKI+PBS)组、BMSCs-Klotho干预(AKI with BMSCs-Klotho intervention,AKI+BMSCs-Klotho)组、BMSCs-EV干预(AKI with BMSCs-EV intervention,AKI+BMSCs-EV)组和BMSCs干预(AKI with BMSCs intervention,AKI+BMSCs)组,所有干预均在造模后6h实施。各组小鼠均在干预治疗3天后处死。常规生化检测血清肌酐(serum creatinine,Scr)及尿素氮(blood urea nitrogen,BUN)水平,利用免疫组织化学法、蛋白印迹法检测肾脏VEGF的表达。结果 与CON组比较,AKI+PBS组、AKI+BMSCs-Klotho组、AKI+BMSCs-EV组和AKI+BMSCs组血清检测Scr(F=370.705,P<0.001;P<0.001;P<0.001;P<0.001)和BUN(F=307.656,P<0.001;P<0.001;P<0.001;P<0.001)水平均升高;AKI+BMSCsKlotho组上述指标低于AKI+PBS组、AKI+BMSCs-EV组及AKI+BMSCs组(Scr:P<0.001;P<0.001;P<0.001;BUN:P<0.001;P<0.001;P<0.001)。蛋白印迹法与免疫组织化学法均检测到AKI+PBS组的肾脏VEGF的表达明显低于CON组(蛋白印迹:P<0.001;免疫组化:P<0.001)。AKI+BMSCs-Klotho组的肾脏VEGF表达高于AKI+PBS组、AKI+BMSCs-EV组和AKI+BMSCs组(蛋白印迹:P<0.001;P<0.001;P<0.001;免疫组化:P<0.001;P<0.001;P<0.001),与CON组比较无统计学差异(蛋白印迹:P=0.884;免疫组化:P=0.809)。结论 Klotho可能通过上调肾脏VEGF表达对AKI小鼠起肾脏保护作用。
文摘Summary： The neuroproteetive effects of escitalopram oxalate in rats with chronic hypoperfusion and the possible mechanism were explored. Chronic hypoperfusion （2-VO） model was prepared and given escitalopram oxalate （experimental group） or PBS （control group） after 6 weeks. Eight weeks after the operation, Morris water maze test was carried out to evaluate the learning and memory ability of the rats. The cell proliferation, three-dimensional vascular distribution, cell morphological changes in ischemic area and the plasma vascular endothelial growth factor （VEGF） were detected to explore the possible mechanisms. （1） Morris water maze test showed that the escape latency in the experimental group was significantly shorter than in the control group, while the first quadrant swimming time in the experi- mental group was significantly longer than the control group （both P〈0.01）. （2） Cerebrovascular confo- cal detection results showed that the inside diameter of capillaries was significantly less in the experi- mental group than in the control group; the vascular density was significantly increased in the experi- mental group and the total area of capillaries was also significantly increased in the experimental group as compared with the control group. （3） There was statistically significant difference in BrdU-positive cells in the ischemic brain tissue between the experimental group and the control group （P=0.003〈0.01）. （4） VEGF concentrations in the plasma and the ischemic area were higher in the experimental group than in the control group （P〈0.05）. It was concluded that escitalopram oxalate could significantly im- prove the learning and memory ability of the rats with chronic cerebral ischemia probably by the VEGF-mediated angiogenesis.
