中药丹参酮对复合痴呆大鼠海马内诱导型一氧化氮合酶和乙酰胆碱酯酶的影响

目的 探讨丹参酮对D-半乳糖- Aβ_(1-40)致复合痴呆模型大鼠海马内诱导型一氧化氮合酶(inducible nitric oxide synthase,iNOS)和乙酰胆碱酯酶(acetylcholinesterase,AChE)表达的影响.方法 ① 实验动物随机分成3组:AD模型组:采用1.25% D-半乳糖腹腔注射致衰老结合双侧海马齿状回背侧微量注射凝聚态Aβ_(1-40)复合造模方法,拟建立AD样学习记忆功能障碍的痴呆动物模型;丹参酮治疗组:AD大鼠造模24 h后给予丹参酮50 mg/(kg·d)];溶媒对照组:与AD大鼠同法注射等量生理盐水.② 采用免疫组织化学和酶组织化学方法,分别观察大鼠海马内iNOS和AChE表达的变化.结果 ①模型组AChE阳性纤维受损,光密度下降(含阳性面积百分比和光密度);iNOS-ir细胞数显著升高,平均光密度增强;与对照组比较差异极显著(P<0.01).②丹参酮处理后,iNOS-ir细胞数明显减少,光密度也下降;AChE阳性神经纤维密度增强;与模型组比较差异有显著性意义(P<0.01).结论 丹参酮改善D-半乳糖- Aβ_(1-40)致复合痴呆大鼠学习记忆障碍的作用机制,可能与保护脑内胆碱能神经,以及降低海马内iNOS的表达有关.

Influence of Tanshinone on Levels of Inos and AChE in Hippocampus of Dementia Rats Induced by D-galactose in Combination with Aβ_(1-40)

Objective To investigate the effect of tanshinone on levels of iNOS and AChE in hippocampus of dementia model rats induced by D-galactose combination with Aβ_(1-40).Methods ①The experimental animals were randomly divided into three groups. In AD model group 1.25%D-galactose in combination with microinjection of 10 μg incubated amyloid β-peptide 1-40 (Aβ_(1-40)) into the dorsal blade of the dentale gyrus in the hippocampus of rat. In tanshinone therapeutic group,after establishment of rat AD model for 24 h , tanshinone50 mg/(kg·d)]was given for 14 days by gastric perfusion. In solvent control group,the rats were treated with the same method as AD rats but received injection of the same physiological saline. ② The expression of iNOS and AChE in rat hippocampus were respectively observed by immunohistochemical and histochemical methods .Results ①AChE positive nervous fibers, optical density of AChE positive nervous fibers of AD rats in the hippocampus were decreased.iNOS-ir cells count and the average optical density of AD rats in the hippocampus were significantly increased as compared with solvent control group. ②After tanshinone treatment, iNOS -ir cell count and the optical density were obviously decreased, optical density of AChE-positive nervous fibers were significantly increased as compared with AD model group.Conclusion Mechanism of tanshinone to improve learning and memory impairment in dementia model rats induced by D-galactose in combination with Aβ_(1-40) might be related to protection of cholinergic nerves in brain and decrease of iNOS expression in hippocampus .