Li Yachen, Bao Yongming, Jiang Bo, Wang Zhuo, Liu Yuxin, Zhang Cen, An Lijia
School of Environmental and Biological Science & Technology, Dalian University of Technology, Dalian, Liaoning, China.
Int J Dev Neurosci. 2008 May-Jun;26(3-4):309-17. doi: 10.1016/j.ijdevneu.2008.01.006. Epub 2008 Jan 31.
Catalpol, an iridoid glycoside abundant in the roots of Rehmannia glutinosa, has been previously found to prevent the loss of CA1 hippocampal neurons and to reduce working errors in gerbils after ischemia-reperfusion injury. In the present study, we investigated the effects of catalpol on astrocytes in an ischemic model to further characterize its neuroprotective mechanisms. Primary cultured astrocytes exposed to oxygen-glucose deprivation (OGD) followed by reperfusion (adding back oxygen and glucose, OGD-R), were used as an in vitro ischemic model. Treatment of the astrocytes with catalpol during ischemia-reperfusion increased astrocyte survival significantly in a concentration-dependent manner, as demonstrated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, lactate dehydrogenase (LDH) release and morphological observation. In addition, catalpol prevented the decrease in mitochondrial membrane potential, inhibited the formation of reactive oxygen species (ROS) and the production of nitric oxide (NO), decreased the level of lipid peroxide and the activity of inducible nitric oxide synthase (iNOS), and elevated the activities of superoxide dismutase (SOD), glutathione peroxidase (GPx) and the content of glutathione (GSH). Our results suggest that catalpol exerts the most significant cytoprotective effect on astrocytes by suppressing the production of free radicals and elevating antioxidant capacity.
梓醇是地黄根中富含的一种环烯醚萜苷，此前已发现它能预防海马CA1区神经元丢失，并减少沙土鼠缺血再灌注损伤后的工作错误。在本研究中，我们在缺血模型中研究了梓醇对星形胶质细胞的影响，以进一步阐明其神经保护机制。将原代培养的星形胶质细胞暴露于氧糖剥夺（OGD）后再灌注（重新添加氧气和葡萄糖，OGD-R），以此作为体外缺血模型。在缺血再灌注期间用梓醇处理星形胶质细胞，通过3-(4,5-二甲基噻唑-2)-2,5-二苯基四氮唑溴盐（MTT）法、乳酸脱氢酶（LDH）释放和形态学观察发现，梓醇能以浓度依赖的方式显著提高星形胶质细胞的存活率。此外，梓醇可防止线粒体膜电位降低，抑制活性氧（ROS）的形成和一氧化氮（NO）的产生，降低脂质过氧化物水平和诱导型一氧化氮合酶（iNOS）的活性，并提高超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GPx）的活性以及谷胱甘肽（GSH）的含量。我们的结果表明，梓醇通过抑制自由基产生和提高抗氧化能力，对星形胶质细胞发挥最显著的细胞保护作用。
