淫羊藿苷改善D-半乳糖诱导的大鼠学习记忆减退
摘要
目的:观察淫羊藿苷(icariin,ICA)对D-半乳糖(D-galactose,D-gal)诱导的大鼠学习记忆减退的作用,并探讨其作用机制。方法:经Morris水迷宫筛选,40只合格的SD大鼠随机分为4组(n=10):空白组、正常给药组、模型组和ICA治疗组。模型组和ICA治疗组大鼠连续颈背部皮下注射10%D-gal(500 mg/kg/d)4个月,空白组和正常给药组大鼠注射等体积生理盐水。第2日起,ICA治疗组和正常给药组大鼠连续ICA灌胃60 mg/kg/d 4个月,空白组和模型组大鼠灌胃等体积蒸馏水。每周观察各组大鼠体重变化,给药结束后,Morris水迷宫检测大鼠空间辨别学习记忆能力,HE染色光镜观察大鼠海马神经元形态变化,光化学法检测大鼠血清和海马组织中SOD活性和MDA含量,real time PCR法检测海马组织SOD2、脑源性神经营养因子(brain-derived neurotrophic factor,BDNF)及其受体TrkB mRNA的表达;Western blotting法捡测海马组织BDNF和TrkB的蛋白表达。结果:D-gal皮下注射4个月后,与空白组比较,模型组大鼠出现明显的空间辨别学习记忆减退,在定位航行实验中逃避潜伏期及搜索距离明显延长,HE染色发现海马神经元排列紊乱,大量神经元变性或丢失;海马组织和血清SOD活性降低,MDA含量增加;海马组织SOD2、BDNF和TrkB mRNA表达降低,BDNF和TrkB蛋白表达减少。与模型组比较,ICA明显缩短大鼠在定位航行实验中的逃避潜伏期及搜索距离;HE染色发现海马神经元较模型组排列整齐,变性、丢失的神经元减少;海马组织和血清SOD活性高于模型组,MDA含量低于模型组;海马组织SOD2、BDNT和TrkB mRNA表达及BDNF和TrkB蛋白表达均高于模型组。ICA对正常大鼠的学习记忆和上述参数无明显影响。结论:ICA可明显减轻D-gal诱导的大鼠学习记忆减退,其机制与抗氧化应激、阻遏BDNF和TrkB mRNA及蛋白表达减少有关。
Objective: To investigate the protective effect of icariin (ICA) on D-galactose (D-gal)-induced learning and memory deficits in rats, and explore the active mechanisms. Methods: Sprague Dawle rats were screened, and qualified 40 of the rats were randomly divided into four groups (n=10), which were the control, normal with ICA, model and model with ICA group, respectively. Model and model with ICA groups were consecutively injected subcutaneously 10% D-gal (500 mg/kg/d) four months, control and normal with ICA were injected normal saline. From the next day of D-gal treatment, the rats of ICA group and the parallel normal control group were administered with ICA (60 mg/kg/d) by gavage. The rats of model and untreated control were given equi-volume of distilled water by gavage. The weight of all rats was recorded per week. After four months, the ability of spatial learning and memory was tested by Morris water maze, the brain tissue was then removed and stained with Hematoxylin-eosin. The activity of superoxide dismutase (SOD) and the content of maloidaldehyde (MDA) in serum and hippocampus were assayed by corresponding kits. The mRNA levels of SOD2, brain-derived neurotrophic factor (BDNP) and tyrosine kinase B (TrkB) were detected by real time PCR, and the expressions of BDNF and TrkB proteins were examined by Western blotting. Results: D-gal administration significantly increased escape latency and searching distance, caused neuronal arrangement disorder, degeneration or even loss in hippocampus. It slowed down the growth of weight, reduced the activity of SOD, but elevated the content of MDA in serum and hippocampus when compared with the control. D-gal also decreased mRNA levels of SOD2, BDNF and TrkB, and reduced protein expressions of BDNF and TrkB in hippocampus, which is indicative of brain dysfunction. However, ICA treatment significantly attenuated D-gal-induced brain dysfunction, as evidenced by shortened escape latency and searching distance, reduced the neuronal injury in hippocampus compared with the model, elevated SOD activity and lowered MDA content in serum and hippocampus, increased the levels of SOD2, BDNF and TrkB mRNA, as well as the protein expressions of BDNF and TrkB in hippocampus. Conclusion: D-gal may decrease the expressions of BDNF and TrkB mRNA and protein in rat. ICA can significantly attenuate learning and memory deficits induced by chronic administration with D-gal. The active mechanisms of ICA may be due to its antioxidative effect, and the up-regulation of BDNF and TrkB mRNAas well as protein expressions.
Objective: To investigate the protective effect of icariin (ICA) on D-galactose (D-gal)-induced learning and memory deficits in rats, and explore the active mechanisms. Methods: Sprague Dawle rats were screened, and qualified 40 of the rats were randomly divided into four groups (n=10), which were the control, normal with ICA, model and model with ICA group, respectively. Model and model with ICA groups were consecutively injected subcutaneously 10% D-gal (500 mg/kg/d) four months, control and normal with ICA were injected normal saline. From the next day of D-gal treatment, the rats of ICA group and the parallel normal control group were administered with ICA (60 mg/kg/d) by gavage. The rats of model and untreated control were given equi-volume of distilled water by gavage. The weight of all rats was recorded per week. After four months, the ability of spatial learning and memory was tested by Morris water maze, the brain tissue was then removed and stained with Hematoxylin-eosin. The activity of superoxide dismutase (SOD) and the content of maloidaldehyde (MDA) in serum and hippocampus were assayed by corresponding kits. The mRNA levels of SOD2, brain-derived neurotrophic factor (BDNP) and tyrosine kinase B (TrkB) were detected by real time PCR, and the expressions of BDNF and TrkB proteins were examined by Western blotting. Results: D-gal administration significantly increased escape latency and searching distance, caused neuronal arrangement disorder, degeneration or even loss in hippocampus. It slowed down the growth of weight, reduced the activity of SOD, but elevated the content of MDA in serum and hippocampus when compared with the control. D-gal also decreased mRNA levels of SOD2, BDNF and TrkB, and reduced protein expressions of BDNF and TrkB in hippocampus, which is indicative of brain dysfunction. However, ICA treatment significantly attenuated D-gal-induced brain dysfunction, as evidenced by shortened escape latency and searching distance, reduced the neuronal injury in hippocampus compared with the model, elevated SOD activity and lowered MDA content in serum and hippocampus, increased the levels of SOD2, BDNF and TrkB mRNA, as well as the protein expressions of BDNF and TrkB in hippocampus. Conclusion: D-gal may decrease the expressions of BDNF and TrkB mRNA and protein in rat. ICA can significantly attenuate learning and memory deficits induced by chronic administration with D-gal. The active mechanisms of ICA may be due to its antioxidative effect, and the up-regulation of BDNF and TrkB mRNAas well as protein expressions.
引文
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6.刘晓秋,李卫东,唐惠琼,等.D-半乳糖衰老大鼠自由基代谢状况分析.中国 老年学杂志,2001;21(6):456-458
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