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目的 探讨维生素A酸(retinoic acid,RA)对大鼠缺血性脑损伤的保护作用及机制.方法 将54只SD大鼠分为假手术组、缺血对照组和RA治疗组,用线栓法将缺血对照组和RA治疗组大鼠制成大脑中动脉闭塞(MCAO)的脑缺血动物模型;应用蛋白免疫印迹法、免疫组织化学方法分别检测大脑皮层内皮型一氧化氮合酶(eNOS)、诱导型一氧化氮合酶(iNOS)[0]表达;用TUNEL法观察凋亡细胞;用电子显微镜观察神经突触.结果 脑缺血后大脑皮层eNOS和iNOS表达均显著上升;RA能上调eNOS表达,使缺血皮层iNOS表达从3.1±1.9(细胞数/62500μm2)降至0.8±0.2(细胞数/62500μm2,P缺血对照组,其数值分别为每平方微米(8.11±0.12)个、(5.26±0.21)个、(1.84±0.33)个(P<0.05).结论 RA通过上调eNOS表达、抑制iNOS表达、抗细胞凋亡和促进神经突触生长而发挥神经保护作用.“,”Objective To study the protection of retinoic acid (RA) against ischemic brain injury in rats and its mechanism. Methods The model of focal cerebral ischemia was established by middle cerebral artery occlusion (MCAO) in SD rats. Fifty-four rats were divided into three groups: sham operation group, ischemia control group and RA treatment group. The animals were sacrificed after cerebral ischemia for seven days. The expression of endothelial NO synthase (eNOS) was detected by Western blot. The inducible NO synthase (iNOS) positive cells were observed by immunohistochemistry. The apoptotic cells were detected by TUNEL staining. The number of synapses was analyzed by transmission electron microscopy. Results The expression of eNOS in ischemic cortex in RA treatment group was significantly higher than that in ischemia control group(P<0.001). Immunohistochemistry revealed iNOS positive cells in ischemic cortex was 3.1±1.9 cells/62500 μm2 in ischemia control group. However,RA treatment remarkably reduced them to 0.8±0.2 cells /62500 μm2 (P<0.05). The apoptotic cells in ischemic cortex fell from 92.8±12.2 cells/62500 μm2 in ischemia control group to 35.5±8.6 cells/62500 μm2 in RA treatment group(P<0.001). The number of synapses at 7 d after MCAO was 8.11±0.12 number /μm2 in sham group, 5.26±0.21 number/μm2 in RA treatment group and 1.84±0.33number/μm2 in ischemia control group, respectively (P<0.05), Conclusion RA has neuroprotection against ischemic brain injury by promoting the expression of eNOS,inhibiting the expression of iNOS,increasing the number of synapses, and its anti-apoptosis action.