目的 探討高良姜素對(duì)阿爾茨海默病（AD）大鼠認(rèn)知障礙及音猬因子/跨膜蛋白受體1（Shh/Ptch1）信號(hào)通路的影響。方法 通過在大腦海馬CA1區(qū)注射Aβ1～42構(gòu)建AD模型，將造模成功大鼠隨機(jī)分為模型組，高良姜素低、高劑量（25、50 mg·kg^-1）組，高良姜素（50 mg·kg^-1）＋環(huán)巴胺（Shh抑制劑，10 mg·kg^-1）組，每組12只，另取12只健康大鼠作為對(duì)照組；高良姜素ig給藥，環(huán)巴胺ip給藥；對(duì)照組與模型組ig等量0.9%氯化鈉溶液，連續(xù)給藥28 d。給藥結(jié)束進(jìn)行Morris水迷宮檢測(cè)； ELISA法檢測(cè)血清炎癥指標(biāo)白細(xì)胞介素（IL）-6、IL-1β及氧化應(yīng)激指標(biāo)丙二醛（MDA）、超氧化物歧化酶（SOD）水平； HE染色檢測(cè)海馬組織病理形態(tài)； TUNEL染色檢測(cè)神經(jīng)元細(xì)胞凋亡情況；免疫組化檢測(cè)海馬組織病理損傷相關(guān)蛋白β淀粉樣蛋白（Aβ）、磷酸化的Tau蛋白（p-Tau）表達(dá)； Western blotting法檢測(cè)海馬組織Shh、Ptch1、GLI家族鋅指蛋白1（GLI1）及凋亡相關(guān)蛋白B細(xì)胞淋巴瘤2（Bcl-2）、Bcl-2相關(guān)X蛋白（BAX）表達(dá)。結(jié)果 模型組較對(duì)照組海馬組織破壞嚴(yán)重，神經(jīng)元形態(tài)不規(guī)則，排列紊亂，神經(jīng)元細(xì)胞核縮小，數(shù)量減少；逃避潛伏期顯著延長、穿越平臺(tái)次數(shù)及在平臺(tái)停留的時(shí)間顯著減少，血清IL-6、IL-1β、MDA水平及神經(jīng)元凋亡率、海馬Bax、Aβ、p-Tau蛋白表達(dá)顯著升高，血清SOD水平及海馬組織Bcl-2、Shh、Ptch1、Gli1蛋白表達(dá)顯著降低，差異均有統(tǒng)計(jì)學(xué)意義（P＜0.05）。高良姜素低、高劑量組較模型組海馬組織破壞減輕，神經(jīng)元形態(tài)異常程度減輕，排列相對(duì)整齊，核固縮減輕，神經(jīng)元丟失減少；逃避潛伏期顯著縮短、穿越平臺(tái)次數(shù)及在平臺(tái)停留的時(shí)間顯著增多，IL-6、IL-1β、MDA水平及神經(jīng)元凋亡率、Bax、Aβ、p-Tau表達(dá)顯著降低，SOD水平及Bcl-2、Shh、Ptch1、Gli1表達(dá)顯著升高，差異均有統(tǒng)計(jì)學(xué)意義（P＜0.05）；高良姜素＋環(huán)巴胺組較高良姜素高劑量組海馬組織破壞加重，逃避潛伏期顯著延長、穿越平臺(tái)次數(shù)及在平臺(tái)停留的時(shí)間顯著減少，IL-6、IL-1β、MDA水平及神經(jīng)元凋亡率、Bax、Aβ、p-Tau表達(dá)顯著升高，SOD水平及Bcl-2、Shh、Ptch1、Gli1表達(dá)顯著降低，差異均有統(tǒng)計(jì)學(xué)意義（P＜0.05）。結(jié)論 高良姜素可改善AD大鼠認(rèn)知障礙，其作用機(jī)制與激活Shh/Ptch1信號(hào)通路相關(guān)。

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

河南省醫(yī)學(xué)教育研究項(xiàng)目（ WJLX2023244）;2024年度河南省高等教育（高等職業(yè)教育類）教學(xué)改革研究與實(shí)踐項(xiàng)目（ 74）;河南省高等學(xué)校重點(diǎn)科研項(xiàng)目（23B320017)