目的 研究洗心汤颗粒对散发性老年性痴呆（SAD）大鼠模型脑内促Tau蛋白毒性形成的重要位点Thr231、Ser422磷酸化的影响，探讨洗心汤颗粒防治SAD的作用机制。方法 将SD大鼠随机分为假手术组，SAD模型组，多奈哌齐阳性对照组，洗心汤颗粒低、中、高剂量（7.61、15.21、30.42 g/kg）组，每天ig给药1次，连续给药2个月。以免疫组化法及Western blotting法检测大鼠脑组织Tau蛋白重要位点Thr231、Ser422的磷酸化水平。结果 与SAD模型组相比，洗心汤颗粒显著减少SAD模型大鼠海马组织Thr231、Ser422的表达（P＜0.05、0.01）；多奈哌齐则无显著作用。结论 洗心汤颗粒抑制Tau蛋白重要位点的过度磷酸化及其Tau蛋白毒性，遏制SAD的病理进展。

Objective To establish sporadic Alzheimer’s disease (SAD) rat model, to investigate the effects of Xixin Decoction Granule (XDG) on the phosphorylation of Thr231 and Ser422 sites as the important promoters of Tau protein toxicity in the brain of SAD rat, and to explore the possible mechanism of XDG on the prevention and treatment of SAD. Methods The SPF male SD rats were randomly divided into Sham (S), model (M), donepezil (D, positive control), low-, mid-, and high-dose XDG (LX, MX, and HX, 7.61, 15.21, and 30.42 g/kg) groups, with ig administration once daily for two months. The immunohistochemistry and Western blotting were used to detect the phosphorylation levels of Thr231 and Ser422 sites in Tau protein in brain of rats with SAD. Results Compared with M group, XDG could significantly decrease the expression of Thr231 and Ser422 sites in the hippocampus of SAD rats (P < 0.05, 0.01). There were no obvious differences between D and M groups (P > 0.05). Conclusion The results suggest that XDG could inhibit the hyperphosphorylation of key sites in site protein and Tau toxicity, so as to prevent SAD pathological progress.

国家自然科学基金资助项目（30973738）