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目的:观察Aβ42沉积对大脑海马CD45、炎症因子和磷酸化tau蛋白(p-tau)表达的影响及白芍总苷(TGP)的干预作用。方法:应用立体定位注射技术对12周龄雌性SD大鼠1次性大脑海马定位注射纤丝状A 42复制AD病理模型,并给予白芍总苷进行干预,用免疫组化方法显示CD45、炎症因子及p-tau表达情况,并用分析软件进行图像分析。结果:与正常对照组相比,AD模型组的CD45、IL-1β、IL-6及p-tau阳性细胞染色面积(染色面积与染色的阳性细胞数成正比)均增加而染色强度值均下降(蛋白表达量与染色强度值成反比);与AD模型组比较,各给药组的IL-1β、IL-6染色面积均下降;除西乐葆对照组的IL-6染色强度值仅表现为增加的趋势外,其余各给药组的IL-1β、IL-6染色强度值均增加。另外,与AD模型组相比,白芍总苷高剂量组和西乐葆组的p-tau、CD45染色面积均下降而染色强度值均升高,TGP低剂量组的p-tau、CD45染色面积则有下降的趋势而染色强度值则有升高的趋势。结论:Aβ42沉积可诱导大脑海马炎症反应、小胶质细胞激活和炎症细胞因子过表达以及tau蛋白的过度磷酸化,而抑制小胶质细胞的激活及炎症细胞因子的过表达,从而抑制脑内炎症及tau蛋白的过度磷酸化,可能是TGP拮抗AD的主要作用机制。
OBJECTIVE: To observe the effect of Aβ42 deposition on the expression of CD45, inflammatory factor and phosphorylated tau protein (p-tau) in hippocampus and the intervention of total glucosides of paeony (TGP). Methods: The stereotactic injection of fibronectin (A 42) in 12-week-old female Sprague-Dawley (SD) rats was performed by stereotaxic injection and the total glucosides of paeony were intervened. The expressions of CD45 and inflammation were detected by immunohistochemistry Factors and p-tau expression, and analysis software for image analysis. Results: Compared with the normal control group, the staining area of CD45, IL-1β, IL-6 and p-tau positive cells in the AD model group increased proportionally (staining area was proportional to the number of stained positive cells) (Protein expression level is inversely proportional to the staining intensity). Compared with AD model group, the staining area of IL-1β and IL-6 decreased in all the groups. Except for Celebrex control group, IL-6 staining intensity showed only The trend of IL-1β, IL-6 staining intensity of other drug groups were increased. In addition, compared with the AD model group, the high-dose total glucosides of paeony glycosides and the group of the Xi Leduo p-tau, CD45 staining area were decreased and staining intensity values were increased, TGP low dose group of p-tau, CD45 staining area There is a downward trend and the dyeing intensity has a tendency to increase. CONCLUSION: Aβ42 deposition can induce hippocampal inflammatory response, microglial activation, overexpression of inflammatory cytokines and hyperphosphorylation of tau while inhibiting activation of microglia and overexpression of inflammatory cytokines, thereby inhibiting intracerebral Inflammation and hyperphosphorylation of tau may be the main mechanism by which TGP antagonizes AD.