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二苯乙烯苷对阿尔茨海默病神经元细胞凋亡的抑制作用
Inhibitory effect of TSG on apoptosis of neuronal cells in rats with Alzheimer’s disease
【摘要】 目的 探讨二苯乙烯苷(2,3,5,4’-tetrahydroxystilbene-2-O-β-D-glycoside, TSG)对阿尔茨海默病神经元细胞凋亡的抑制情况。方法 选取24月龄SPF级SD大鼠随机分为7组,分别为正常组、假手术组、模型组、阳性药组(0.150 mg/kg石杉碱甲)、TSG低剂量组(0.033 g/kg TSG)、TSG中剂量组(0.100 g/kg TSG)、TSG高剂量组(0.300 g/kg TSG)。模型组、阳性药组与TSG各剂量组通过大鼠脑立体定位仪选取海马区域注射Aβ25-35溶液建立AD大鼠模型,假手术组注射等量生理盐水,正常组不做处理。经被动回避实验筛选造模成功的SD大鼠,每组每日灌胃给药1次,连续给药4周。通过TUNEL凋亡实验观察大鼠海马区和皮层区神经元细胞凋亡的情况;实时荧光定量聚合酶链式反应法(qRT-PCR)检测各组大鼠脑组织Bax、Bcl-2 mRNA的表达;免疫组织化学染色法(IHC)检测各组大鼠脑组织Bax、Bcl-2蛋白的表达。结果 与正常组比较,假手术和阳性药组脑组织中海马区和皮层区神经元细胞凋亡情况无明显变化,假手术组Bax、Bcl-2 mRNA相对表达量和Bax、Bcl-2蛋白表达无显著改变;模型组脑组织中海马区和皮层区神经元细胞凋亡情况出现增多,Bax mRNA相对表达量和Bax蛋白表达出现增多(P<0.01),Bcl-2 mRNA相对表达量和Bcl-2蛋白表达出现减少(P<0.01);与模型组比较,阳性药组和TSG各剂量组脑组织中海马区和皮层区神经元细胞凋亡情况出现不同程度的好转,Bax mRNA相对表达量和Bax蛋白表达出现不同程度的减少(P<0.05),Bcl-2 mRNA相对表达量和Bcl-2蛋白表达出现不同程度的增多(P<0.05)。结论 TSG可以通过调节凋亡途径中Bax、Bcl-2因子来达到减少神经元细胞凋亡的情况,增加对神经系统的保护,达到缓解阿尔茨海默病症状的可能性。
【Abstract】 Objective To investigate the inhibitory effects of 2,3,5,4’-tetrahydroxystilbene-2-O-β-D-glycoside(TSG) on neuronal cell apoptosis in rats with Alzheimer’s disease. Methods SPF-grade SD rats aged 24 months were randomly divided into 7 groups, including the normal group, sham operation group, model group, positive drug group(0.150 mg/kg huperzine A), low-dose TSG group(0.033 g/kg TSG), medium-dose TSG group(0.100 g/kg TSG), and high-dose TSG group(0.300 g/kg TSG). The model group, positive drug group, and TSG groups were injected with Aβ25-35 solution in the hippocampus region using a rat brain stereotaxic instrument to establish an Alzheimer’s disease(AD) rat model, while the sham operation group was injected with an equal volume of physiological saline, and the normal group received no treatment. After passive avoidance test, the successfully modeled SD rats were orally administered with the respective drugs once daily for 4 weeks. TUNEL apoptosis assay was used to observe the apoptosis of neuronal cells in hippocampus and cortical areas of rats. Real-time quantitative polymerase chain reaction(qRT-PCR) was used to detect the expression of Bax and Bcl-2 mRNA in rat brain tissues of each group, and immunohistochemical staining(IHC) was used to detect the expression of Bax and Bcl-2 proteins in rat brain tissues of each group. Results Compared with the normal group, there was no significant change in the apoptosis of neuronal cells in the hippocampus and cortical areas, as well as the relative expression levels of Bax and Bcl-2 mRNA and protein in the brain tissues of the sham operation group and positive drug group. In the model group, the apoptosis of neuronal cells in the hippocampus and cortical areas increased significantly, with increased relative expression levels of Bax mRNA and protein(P<0.01), and decreased relative expression levels of Bcl-2 mRNA and protein(P<0.01). Compared with the model group, the positive drug group and TSG groups had varying degrees of improvement in the apoptosis of neuronal cells in the hippocampus and cortical areas, and had decreased relative expression levels of Bax mRNA and protein(P<0.05) and increased relative expression levels of Bcl-2 mRNA and protein(P<0.05). Conclusion TSG may reduce neuronal cell apoptosis and increase protection of the nervous system by regulating the apoptotic pathway involving Bax and Bcl-2 factors, and may have the potential to alleviate the symptoms of Alzheimer’s disease.
【Key words】 Alzheimer’s disease; 2,3,5,4’-tetrahydroxystilbene-2-O-β-D-glycoside; Bcl-2-associated X protein; B-cell lymphoma-2;
- 【文献出处】 右江民族医学院学报 ,Journal of Youjiang Medical University for Nationalities , 编辑部邮箱 ,2023年02期
- 【分类号】R749.16
- 【下载频次】95