目的探讨山奈酚(kaempferol,KAE)对慢性脑缺血大鼠的作用及其机制。方法采用双侧颈总动脉永久性结扎(bilateral common carotid arteries occlusion,2VO)建立大鼠慢性脑缺血动物模型;Morris水迷宫、抓握实验检测大鼠行为学;尼氏染色及H...目的探讨山奈酚(kaempferol,KAE)对慢性脑缺血大鼠的作用及其机制。方法采用双侧颈总动脉永久性结扎(bilateral common carotid arteries occlusion,2VO)建立大鼠慢性脑缺血动物模型;Morris水迷宫、抓握实验检测大鼠行为学;尼氏染色及HE染色观察脑组织病理改变;比色法检测MDA含量和SOD活性;Western blot检测脑组织DJ-1蛋白表达水平。结果与2-VO模型组比较,KAE明显改善慢性脑缺血诱导的学习记忆障碍和抓握能力损伤。此外,KAE明显减轻2VO大鼠脑组织病理损伤,增高脑组织中SOD活性,提高海马和皮层中抗氧化蛋白DJ-1的表达水平。结论KAE明显改善慢性脑缺血诱导的大鼠认知功能障碍、四肢平衡能力障碍及病理损伤,其机制可能与提高体内抗氧化系统有关。展开更多
The Rho/Rho-kinase signaling pathway plays an important role in cerebral ischemia/reperfusion injury. However, very few studies have examined in detail the changes in the Rho/Rho-kinase signaling pathway in chronic ce...The Rho/Rho-kinase signaling pathway plays an important role in cerebral ischemia/reperfusion injury. However, very few studies have examined in detail the changes in the Rho/Rho-kinase signaling pathway in chronic cerebral ischemia. In this study, rat models of chronic cerebral ischemia were established by permanent bilateral common carotid artery occlusion and intra- gastrically administered 9 mg/kg fasudil, a powerful ROCK inhibitor, for 9 weeks. Morris water maze results showed that cognitive impairment progressively worsened as the cerebral ischemia proceeded. Immunohistochemistry, semi-quantitative RT-PCR and western blot analysis showed that the expression levels of Rho-kinase, its substrate myosin-binding subunit, and its relat- ed protein alpha smooth muscle actin, significantly increased after chronic cerebral ischemia. TUNEL staining showed that chronic cerebral ischemia could lead to an increase in neuronal apoptosis, as well as the expression level of caspase-3 in the frontal cortex of rats subjected to chronic cerebral ischemia. Fasudil treatment alleviated the cognitive impairment in rats with chronic cerebral ischemia, and decreased the expression level of Rho-kinase, myosin-binding subunit and alpha smooth muscle actin. Furthermore, fasudil could regulate cerebral injury by reducing cell apoptosis and decreasing caspase-3 expression in the frontal cortex. These findings demonstrate that fasudil can protect against cognitive impairment induced by chronic cerebral ischemia via the Rho/Rho-kinase signaling pathway and anti-apoptosis mechanism.展开更多
基金supported by the Natural Science Foundation of Jilin Province of China,No.200705272,20140414028GH
文摘The Rho/Rho-kinase signaling pathway plays an important role in cerebral ischemia/reperfusion injury. However, very few studies have examined in detail the changes in the Rho/Rho-kinase signaling pathway in chronic cerebral ischemia. In this study, rat models of chronic cerebral ischemia were established by permanent bilateral common carotid artery occlusion and intra- gastrically administered 9 mg/kg fasudil, a powerful ROCK inhibitor, for 9 weeks. Morris water maze results showed that cognitive impairment progressively worsened as the cerebral ischemia proceeded. Immunohistochemistry, semi-quantitative RT-PCR and western blot analysis showed that the expression levels of Rho-kinase, its substrate myosin-binding subunit, and its relat- ed protein alpha smooth muscle actin, significantly increased after chronic cerebral ischemia. TUNEL staining showed that chronic cerebral ischemia could lead to an increase in neuronal apoptosis, as well as the expression level of caspase-3 in the frontal cortex of rats subjected to chronic cerebral ischemia. Fasudil treatment alleviated the cognitive impairment in rats with chronic cerebral ischemia, and decreased the expression level of Rho-kinase, myosin-binding subunit and alpha smooth muscle actin. Furthermore, fasudil could regulate cerebral injury by reducing cell apoptosis and decreasing caspase-3 expression in the frontal cortex. These findings demonstrate that fasudil can protect against cognitive impairment induced by chronic cerebral ischemia via the Rho/Rho-kinase signaling pathway and anti-apoptosis mechanism.
