| 摘 要： | Objective: Huannao Yicong Decoction(还脑益聪方, HYD), an effective herbal formula against Alzheimer's disease(AD), has been proven to have neuroprotective action in amyloid β-protein_(1-42))(Aβ_(1-42))-induced rat model. This study was designed to characterize mechanisms by which HYD leads to suppression of inflammation and apoptosis in the brains of Aβ_(1-42)-induced rat. Methods: A total of 72 rats were divided into 6 groups, which were referred to as: sham operation group, model group, donepezil-treated group, HYD low-dose group(HYDL), HYD middle-dose group(HYDM) and HYD high-dose group(HYDH). Rats in HYDL, HYDM and HYDH were injected with Aβ_(1-42) at the CA1 region of hippocampus to form AD model and were fed the HYD extract at different dose of 3.78, 7.56 and 18.90 g crude drug/kg. The behavioral changes of rats were evaluated by Morris water maze(MWM) before sacrifice. Pathological changes of the brain tissue were evaluated using hematoxylin eosin(HE) staining. The levels of interleukin-1(IL-1) and tumor necrosis factor-α(TNF-α) were measured by radioimmunoassay. The levels of Aβ and proteins that are associated with apoptosis such as B-cell lymphoma-2 protein(Bcl-2), Bcl-2-associated X protein(Bax), cysteine-aspartic protease(caspase)-3,-8,-9 and-12 in serum were measured by immunohistochemistry. Results: Compared with the sham operation group, the spatial learning and memory abilities of AD rats were significantly decreased(P0.05 or P0.01; Expressions of IL-1, TNF-α, Aβ and apoptosis-signaling proteins caspase-3,-8,-9,-12 were significantly up-regulated(P0.05 or P0.01). The ratio of Bcl-2 to Bax were significantly decreased in the model group(P0.01). When treated with HYD extract, the spatial learning and memory abilities of AD-model rats were significantly increased(P0.05 or P0.01), IL-1, TNF-α, Aβ, caspase-3,-8,-9 and-12 were down-regulated(P0.05 or P0.01), and the ratio of Bcl-2 to Bax were reduced(P0.05 or P0.01). Conclusions: HYD extract can improve the learning and memory ability deficits, alleviate the inflammatory response and pathological manifestations induced by Aβ_(1-42) injection in the rat model of AD. HYD down-regulates the levels of IL-1, TNF-α and Aβ, and decreases the rate of apoptosis by modulating apoptosis-signaling-related proteins such as caspase-3,-8,-9, and-12.
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