目的 探讨高良姜素对阿尔茨海默病（AD）大鼠认知障碍及音猬因子/跨膜蛋白受体1（Shh/Ptch1）信号通路的影响。方法 通过在大脑海马CA1区注射Aβ1～42构建AD模型，将造模成功大鼠随机分为模型组，高良姜素低、高剂量（25、50 mg·kg^-1）组，高良姜素（50 mg·kg^-1）＋环巴胺（Shh抑制剂，10 mg·kg^-1）组，每组12只，另取12只健康大鼠作为对照组；高良姜素ig给药，环巴胺ip给药；对照组与模型组ig等量0.9%氯化钠溶液，连续给药28 d。给药结束进行Morris水迷宫检测； ELISA法检测血清炎症指标白细胞介素（IL）-6、IL-1β及氧化应激指标丙二醛（MDA）、超氧化物歧化酶（SOD）水平； HE染色检测海马组织病理形态； TUNEL染色检测神经元细胞凋亡情况；免疫组化检测海马组织病理损伤相关蛋白β淀粉样蛋白（Aβ）、磷酸化的Tau蛋白（p-Tau）表达； Western blotting法检测海马组织Shh、Ptch1、GLI家族锌指蛋白1（GLI1）及凋亡相关蛋白B细胞淋巴瘤2（Bcl-2）、Bcl-2相关X蛋白（BAX）表达。结果 模型组较对照组海马组织破坏严重，神经元形态不规则，排列紊乱，神经元细胞核缩小，数量减少；逃避潜伏期显著延长、穿越平台次数及在平台停留的时间显著减少，血清IL-6、IL-1β、MDA水平及神经元凋亡率、海马Bax、Aβ、p-Tau蛋白表达显著升高，血清SOD水平及海马组织Bcl-2、Shh、Ptch1、Gli1蛋白表达显著降低，差异均有统计学意义（P＜0.05）。高良姜素低、高剂量组较模型组海马组织破坏减轻，神经元形态异常程度减轻，排列相对整齐，核固缩减轻，神经元丢失减少；逃避潜伏期显著缩短、穿越平台次数及在平台停留的时间显著增多，IL-6、IL-1β、MDA水平及神经元凋亡率、Bax、Aβ、p-Tau表达显著降低，SOD水平及Bcl-2、Shh、Ptch1、Gli1表达显著升高，差异均有统计学意义（P＜0.05）；高良姜素＋环巴胺组较高良姜素高剂量组海马组织破坏加重，逃避潜伏期显著延长、穿越平台次数及在平台停留的时间显著减少，IL-6、IL-1β、MDA水平及神经元凋亡率、Bax、Aβ、p-Tau表达显著升高，SOD水平及Bcl-2、Shh、Ptch1、Gli1表达显著降低，差异均有统计学意义（P＜0.05）。结论 高良姜素可改善AD大鼠认知障碍，其作用机制与激活Shh/Ptch1信号通路相关。

Objective To investigate the effects of galangin on cognitive impairment and the sonic hedgehog/transmembrane protein receptor 1 (Shh/Ptch1) signaling pathway in Alzheimer's disease (AD) rats. Methods An AD model was established by injecting Aβ1~42 into the CA1 region of the hippocampus. The successfully modeled rats were randomly divided into the model group, lowdose (25 mg·kg^-1) and high-dose (50 mg·kg^-1) groups of galangin, and the galangin (50 mg·kg^-1) + cyclopamine (Shh inhibitor, 10 mg·kg^-1) group, with 12 rats in each group. Another 12 healthy rats were used as the control group. Galangin was ig administrated and cyclopamine was ip administrated. The control and model groups were ig given the same volume of 0.9% sodium chloride solution. The treatment lasted for 28 days. After the treatment, Morris water maze test was conducted; ELISA was used to detect serum inflammatory markers IL-6 and IL^-1β and oxidative stress markers MDA and SOD levels; HE staining was performed to examine the pathological morphology of the hippocampus; TUNEL staining was used to detect neuronal apoptosis; and immunohistochemistry was conducted to detect the expression of Aβ and p-Tau, which are related to pathological damage in the hippocampus. Western blotting was used to detect the expression of Shh, Ptch1, GLI1, and apoptosis-related proteins Bcl-2 and BAX in the hippocampus. Results The AD group had more severe damage to hippocampal tissue compared to the control group, the morphology of neurons was irregular, the arrangement was disordered, the nuclei of neurons shrank, and the number decreased, the escape latency was prolonged, the number of platform crossings and the duration of stay on the platform decreased, the swimming trajectory is complex, the levels of IL-6, IL- 1β, MDA, neuronal apoptosis rate, the expression of Bax, Aβ, and p-Tau elevated, the level of SOD and the expression of Bcl-2, Shh, Ptch1, and Gli1 decreased, and the differences were statistically significant (P < 0.05). Compared with model group, galangin high and low dose group had less destruction of hippocampal tissue, less abnormal morphological degree of neurons, relatively neat arrangement, less nuclear shrinkage, and less loss of neurons, the escape latency was shortened, the number of platform crossings and the duration of stay on the platform increased, the swimming track is simple, the levels of IL-6, IL^-1β, MDA, neuronal apoptosis rate, the expression of Bax, Aβ, and p-Tau reduced, the level of SOD and the expression of Bcl-2, Shh, Ptch1, and Gli1 increased, and the differences were statistically significant (P < 0.05). The damage to hippocampal tissue was more severe in the galangin + cyclopamine group compared to the galangin high dose group, the escape latency was prolonged, the number of platform crossings and the duration of stay on the platform decreased, the swimming trajectory is complex, the levels of IL-6, IL^-1β, MDA, neuronal apoptosis rate, the expression of Bax, Aβ, and p-Tau increased, the level of SOD and the expression of Bcl-2, Shh, Ptch1, and Gli1 decreased, and the differences were statistically significant (P < 0.05). Conclusion Galangin can improve cognitive impairment in AD rats, and its mechanism of action is related to the activation of the Shh/Ptch1 signaling pathway.

R285.5

河南省医学教育研究项目（ WJLX2023244）;2024年度河南省高等教育（高等职业教育类）教学改革研究与实践项目（ 74）;河南省高等学校重点科研项目（23B320017)