蛇床子素降低磷酸二酯酶含量改善β淀粉样蛋白25-35片段诱导的大鼠神经毒性  

Osthole ameliorates β-amyloid 25-35-induced neurotoxicity through decreasing the content of phosphodiesterase in rat model

作　　者：李小慧[1] 邓媛媛[1] 石京山[1] 杨丹莉[1] 龚其海[1] 

机构地区：[1]遵义医学院药理学教研室暨基础药理省部共建教育部重点实验室,贵州遵义563099

出　　处：《遵义医学院学报》2015年第4期359-362,共4页Journal of Zunyi Medical University

基　　金：教育部"长江学者和创新团队发展计划"创新团队项目(NO:IRT1197);贵州省科技厅优秀青年科技人才资金项目(NO:黔科合人字[2013]26)

摘　　要：目的观察蛇床子素(Ost)抗β淀粉样蛋白(β-amyloid,Aβ)25-35片段诱导的大鼠神经毒性作用并探讨其可能机制。方法雄性SD大鼠30只随机分为假手术组、模型组、Ost(40 mg/kg)治疗组(n=10)。双侧海马注射Aβ25-35建立大鼠神经毒性模型,连续Ost(40 mg/kg)灌胃15 d。每组大鼠随机选取3只进行尼氏染色观察其海马尼氏小体的变化。其余大鼠采用酶联免疫吸附实验(ELISA)测定海马磷酸二酯酶(PDE)及PDE2、PDE4、PDE5、PDE7、PDE9的含量变化。结果模型组大鼠海马的尼氏小体较假手术组皱缩,排列不整齐,甚至消失;而Ost治疗组海马神经元排列较整齐,变性神经元减少。同时,ELISA结果表明,模型组中大鼠海马PDE、PDE4及PDE5的含量较假手术组显著增高(P<0.01);但经Ost治疗后,其水平均有所降低(P<0.01,P<0.05),而对PDE2、PDE7和PDE9的含量没有影响。结论 Ost可抗Aβ25-35所致的大鼠神经毒性,其机制可能与抑制PDE4和PDE5的蛋白表达有关。Objective To investigate the effect of osthole on 25- 35 fragment of beta- amyloid（ Aβ25- 35）- induced neurotoxicity in rats and explore its possible mechanism. Methods Male SD rats were randomly divided into sham group,control group,osthole treatment group（ each group n = 10）. The rat model with neurotoxicity was induced by injecting Aβ25- 35 into the hippocampus. Then rats were intragastric administered with osthole or volume- matched vehicle for 15 d after Aβ25- 35 injection. The change of nissl bodies in the hippocampus CA1 region was investigated by Nissl staining,and the contents of phosphodiesterase（ PDE）,PDE2,PDE4,PDE5,PDE7 and PDE9 were determined using ELISA after rats were sacrificed. Results The pyramidal layer of cells were shrinkaged,irregular arranged or even disappeared in model group compared with sham operation group.Treatment with osthole was significantly reduced neuronal morphological impairment. Then,the contents of PDE,PDE4 and PDE5 in control group were higher than those in sham group（ P〈0. 01）. However,the level of PDE,PDE4 and PDE5 protein in the hippocampus of rats were significantly reduced in osthole treatment group compared with those in control group（ P〈0. 01,P〈0. 05）. But the contents of PDE2,PDE7 and PDE9 were not altered obviously. Conclusion Osthole decreases the neurotoxicity induced by Aβ25- 35 in rats,and its underlying mechanism may be related to inhibition of the expression of PDE4 and PDE5.

关 键 词：蛇床子素 Β淀粉样蛋白25-35 磷酸二酯酶 大鼠 

分 类 号：R961[医药卫生—药理学]