摘要
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(e NOS)、诱导型一氧化氮合酶(i NOS)[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e NOS和i NOS表达均显著上升;RA能上调e NOS表达,使缺血皮层i NOS表达从3.1±1.9(细胞数/62500μm2)降至0.8±0.2(细胞数/62500μm2,P<0.05);缺血皮层细胞凋亡数从缺血对照组的92.8±12.2[TUNEL(+)细胞数/62500μm2]下降至RA治疗组35.5±8.6[TUNEL(+)细胞数/62500μm2,P<0.001]。突触数量比较:假手术组>RA治疗组>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e NOS表达、抑制i NOS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 μm^2 in ischemia control group. However, RA treatment remarkably reduced them to 0.8±0.2 cells/62500 μm^2 （P〈0.05）. The apoptotic cells in ischemic cortex fell from 92.8±12.2 cells/62500 μm^2 in ischemia control group to 35.5±8.6 cells/62500 μm^2 in RA treatment group （P〈0.001） . The number of synapses at 7 d after MCAO was 8.11±0.12 number/μm^2 in sham group, 5.26±0.21 number/μm^2 in RA treatment group and 1.84±0.33number/μm^2 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.
出处
《营养学报》
CAS
CSCD
北大核心
2017年第6期579-582,587,共5页
Acta Nutrimenta Sinica
基金
湖北省自然科学基金(No.2016CFB626)
