Yao R-Q, Zhang L, Wang W, Li L
Department of Pharmacology, Xuanwu Hospital of Capital Medical University, Key Laboratory for Neurodegenerative Diseases of Ministry of Education, 45 Chang-chun Street, Beijing 100053, PR China.
Brain Res Bull. 2009 Apr 6;79(1):69-76. doi: 10.1016/j.brainresbull.2008.12.010. Epub 2009 Jan 15.
The aim of this study was to investigate the effects of cornel iridoid glycoside (CIG), an ingredient extracted from a traditional Chinese herb Cornus officinalis, on neurological function and neurogenesis after ischemic stroke. CIG was intragastrically administered to rats in doses of 20, 60 and 180 mg/kg/day, starting 3 h after the onset of middle cerebral artery occlusion (MCAO). The behavioral test was performed by using the modified neurological severity score (mNSS). Rats were sacrificed 7, 14, or 28 days after ischemia occurred. Neurogenesis and angiogenesis were detected by using immunofluorescence staining. The messenger ribonucleic acid (mRNA) expression of vascular endothelial growth factor (VEGF) and its receptor Flk-1 was measured by RT-PCR, and the protein expression of VEGF was determined by Western blotting analysis. The treatment with CIG at the doses of 60 and 180 mg/kg/day significantly improved neurological function, and increased the number of bromodeoxyuridine (BrdU)-positive cells and nestin-positive cells in the subventricular zone of rats 7, 14 and 28 days after ischemia. The number of newly mature neurons and blood vessels in striatum, as indicated by BrdU/NeuN and vWF immunoreactivity, respectively, was also increased in CIG-treated rats 28 days after stroke. CIG treatment obviously enhanced the mRNA expression of VEGF and its receptor Flk-1 and the protein expression of VEGF 7 and 28 days after ischemia. The results indicated that CIG promoted neurogenesis and angiogenesis and improved neurological function after ischemia in rats, and the mechanism might be related to CIG's increasing VEGF and Flk-1 in the brain.
本研究旨在探讨从传统中药山茱萸中提取的成分山茱萸环烯醚萜苷（CIG）对缺血性脑卒中后神经功能和神经发生的影响。在大脑中动脉闭塞（MCAO）发作后3小时开始，以20、60和180mg/kg/天的剂量对大鼠进行CIG灌胃给药。采用改良神经功能缺损评分（mNSS）进行行为测试。在缺血发生后7、14或28天处死大鼠。通过免疫荧光染色检测神经发生和血管生成。采用逆转录聚合酶链反应（RT-PCR）检测血管内皮生长因子（VEGF）及其受体Flk-1的信使核糖核酸（mRNA）表达，并通过蛋白质印迹分析测定VEGF的蛋白表达。60和180mg/kg/天剂量的CIG治疗显著改善了神经功能，并增加了缺血后7、14和28天大鼠脑室下区溴脱氧尿苷（BrdU）阳性细胞和巢蛋白阳性细胞的数量。在中风后28天，CIG治疗的大鼠纹状体中新成熟神经元和血管的数量也分别通过BrdU/NeuN和vWF免疫反应性增加。CIG治疗明显增强了缺血后7天和28天VEGF及其受体Flk-1的mRNA表达以及VEGF的蛋白表达。结果表明，CIG促进了大鼠缺血后的神经发生和血管生成并改善了神经功能，其机制可能与CIG增加脑中VEGF和Flk-1有关。
