雷公藤内酯醇对阿尔茨海默病模型大鼠海马iNOS表达和突触超微结构的影响

摘要

Objective To explore the effects of triptolide on the expression of inducible nitric oxide synthase ( iNOS) and synaptic ultrastructure in hippocampus of model rats with Alzheimer's disease (AD).Methods Twenty-one male SD rats were equally divided into control ,AD model and triptolide-treated groups .The AD model group were made with unilateral microinjection of aggregated beta-amyloid pro-tein( Aβ) 1~40 into hippocampus in rats and the control group rats were injected with normal saline in the same way .The triptolide-treated group rats were administered triptolide intraperitoneally after microinjection of aggregated Aβ1~40 into hippocampus .The iNOS expression and synaptic ultrastructure in hippocampus of each group were assayed by immunohistochemical staining and transmission electron microscope . Results Immunohistochemically ,the cell number and average optical density of iNOS positive staining in the AD model group were higher than those of control group (P<0.01),the average optical density of iNOS positive staining in the triptolide-treated group were lower than that of AD model group(P<0.05).The number of synapses and synaptic vesicles and the thickness of postsynaptic density of hippocampal neuro -pil in the AD model group were lower than those of control group .The number of synapses and synaptic vesicles and the thickness of postsyn -aptic density of hippocampal neuropil in the triptolide-treated group were higher than those of AD model group .Conclusions Triptolide could inhibit iNOS expression and alleviate the degeneration of synapses in hippocampus of model rats with AD .%目的：观察应用β淀粉样蛋白（ Aβ）后大鼠海马诱导型一氧化氮合酶（ iNOS）的表达和突触超微结构的变化及雷公藤内酯醇对其的影响。方法21只SD雄性大鼠等分成对照组、模型组、用药组。在大鼠左侧海马定向注射凝聚态 Aβ1～40作为模型组，注射等量生理盐水设为对照组，大鼠在海马注射凝聚态Aβ1～40后腹腔注射雷公藤内酯醇为用药组。应用免疫组织化学方法检测各组大鼠海马 iNOS的表达；应用透射电镜观察各组大鼠海马突触超微结构的变化。结果免疫组织化学染色显示，模型组大鼠海马iNOS阳性细胞数和平均光密度明显高于对照组（P＜0．01），用药组大鼠海马iNOS阳性细胞平均光密度较模型组明显降低（P＜0．05）。透射电镜结果显示，模型组大鼠海马神经毡内突触和突触小泡数量较对照组减少，突触后致密物厚度变薄；用药组大鼠海马神经毡内突触和突触小泡数量较模型组增多，突触后致密物增厚。结论雷公藤内酯醇可以抑制Aβ诱导的大鼠海马iNOS的表达，对突触超微结构的损伤有一定的改善作用。