山楂叶总黄酮抑制慢性脑缺血模型大鼠脑组织神经元的凋亡（英文）

Total Flavone of Hawthorn Leaf inhibits neuronal apoptosis in brain tissue of rat models of chronic cerebral ischemia

背景:脑血管疾病常引起大脑神经功能缺失,而神经细胞凋亡是造成脑神经功能缺失的重要因素,c-fos的过度表达能阻断细胞内信号的转导而产生一些促调亡因子,参与脑缺血损伤后的神经细胞凋亡过程,Bcl-2是抑制细胞凋亡因子,抑制或减少损伤后神经细胞凋亡可能成为缺血性脑血管病治疗的关键。目的:探索山楂叶总黄酮对慢性脑缺血模型大鼠的治疗作用及机制。方法:72只健康雄性SD大鼠随机等分为假手术组、模型组、山楂叶总黄酮组和银杏叶片组。后3组大鼠采用永久性双侧颈总动脉结扎法制备脑缺血模型。山楂叶总黄酮组和银杏叶片组大鼠分别于造模后36 d起连续36 d灌胃140 mg/kg山楂叶总黄酮和12.3 mg/kg银杏叶片,而模型组和假手术组大鼠灌胃3.5 m L/kg生理盐水。结果与结论:与模型组比较,山楂叶总黄酮组模型大鼠缺血脑组织中c-fos表达水平显著降低(P<0.01),Bcl-2表达水平显著增加(P<0.01),Ca2+含量降低(P<0.05),且上述指标与银杏叶片组比较差异无显著性意义(P>0.05)。提示山楂叶总黄酮对慢性脑缺血的保护作用与抑制脑神经细胞凋亡有关,其抗凋亡的机制可能与上调Bcl-2表达,下调c-fos表达,降低脑组织Ca2+含量有关。

BACKGROUND： Cerebrovascular disease often causes dysfunction of the brain nerve, and nerve cel apoptosis is the important factor of cerebral nerve dysfunction. The excessive expression of c-fos can block the transduction of intracelular signal so that producing some apoptosis-promoting factors, which involve in nerve cel apoptosis process after ischemia injury of brain. Bcl-2 is an inhibited factor. It might to be the key to treat ischemic cerebrovascular disease by inhibiting or reducing the apoptosis of nerve cels after ischemia injury. OBJECTIVE： To investigate the therapeutic effect and mechanism of the Total Flavone of Hawthorn Leaf on chronic cerebral ischemia rats. METHODS： A total of 72 healthy male Sprague-Dawley rats were randomly divided into sham surgery group, model group, Total Flavone of Hawthorn Leaf group and ginkgo leaf group. Permanent bilateral carotid artery ligation was used to prepare chronic cerebral ischemia model in the model group, Total Flavone of Hawthorn Leaf group and ginkgo leaf group. Total Flavone of Hawthorn Leaf group and ginkgo leaf group respectively received 140 mg/kg Total Flavone of Hawthorn Leaf and 12.3 mg/kg ginkgo leaf intragastricaly for 36 days from 36 days after model induction. Model group and sham surgery group received 3.5 mL/kg physiological saline intragastricaly. RESULTS AND CONCLUSION： Compared with the model group, the expression of c-fos protein significantly deceased in the Total Flavone of Hawthorn Leaf group （P ＆lt; 0.01）, Bcl-2 expression levels significantly increased （P ＆lt; 0.01）, and Ca2＋ content decreased （P ＆lt; 0.05）. Moreover, no significant difference in above indexes was detected between Total Flavone of Hawthorn Leaf group and ginkgo leaf group （P〈 0.05）. These data indicated that the protective effect of Total Flavone of Hawthorn Leaf on chronic cerebral ischemia was associated with its inhibition of neuronal apoptosis. Its mechanism of anti-apoptosis might be associated with up-regulating expression of Bcl-2, down-regulating expression of c-fos and decreasing Ca2＋ content in brain.