黄腐酚调节CaMKK2/AMPK信号通路对急性脑梗死大鼠神经元凋亡及炎症反应的影响

doi:10.3969/j.issn.1006-6233.2025.12.05

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摘要 目的: 探究黄腐酚调节钙/钙调蛋白依赖性蛋白激酶激酶2(CaMKK2)/AMP活化蛋白激酶(AMPK)信号通路对急性脑梗死大鼠神经元凋亡及炎症反应的影响。方法: 本研究通过大脑中动脉闭塞构建急性脑梗死模型,并分为脑梗死组、低剂量(L)黄腐酚(25mg/kg)组、高剂量(H)黄腐酚组(50mg/kg)、H-黄腐酚+抑制剂组,每组12只,给药28d;另取12只健康大鼠为正常组。利用Longa评分法对大鼠进行神经功能评估;TTC染色测量脑梗死体积;HE和TUNEL染色观察大鼠脑组织病变及细胞凋亡;ELISA检测大鼠脑匀浆中炎症因子白介素(IL)-1β、肿瘤坏死因子α(TNF-α)、IL-6的水平;Western blot检测CaMKK2和AMPK相关蛋白表达。结果: 与正常组相比,脑梗死组大鼠神经功能评分提高,脑组织出现梗死,细胞凋亡率、IL-1β、TNF-α、IL-6水平提高,p-CaMKK2和p-AMPK表达降低(P<0.05);与脑梗死组相比,L-黄腐酚组、H-黄腐酚组大鼠神经功能评分降低,脑梗死体积减小,脑组织损伤减轻,细胞凋亡率、IL-1β、TNF-α、IL-6水平降低,p-CaMKK2和p-AMPK表达提高(P<0.05),且H-黄腐酚治疗效果优于L-黄腐酚(P<0.05);而CaMKK2抑制剂STO-609消除了黄腐酚对急性脑梗死大鼠神经元凋亡及炎症反应的抑制(P<0.05)。结论: 黄腐酚可能通过激活CaMKK2/AMPK信号通路减轻急性脑梗死大鼠神经元凋亡及炎症反应。

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	常亮
	李明
	李晶
	刘照寒

关键词 ：急性脑梗死, 黄腐酚, 神经元凋亡, CaMKK2/AMPK信号通路

Abstract：Objective: To explore the effects of xanthohumol on neuronal apoptosis and inflammatory response in rats with acute cerebral infarction by regulating calcium/calmodulin dependent protein kinase 2 (CaMKK2)/AMP-activated protein kinase (AMPK) signaling pathway. Methods: In this study, an acute cerebral infarction model was established by occlusion of the middle cerebral artery, and was assigned into the cerebral infarction group, the low-dose (L) xanthohumol group (25mg/kg), the high-dose (H) xanthohumol group (50mg/kg), and the H-xanthohumol+inhibitor group, with 12 rats in each. The medication was administered for 28days. Another 12 healthy rats were made the normal group. Longa scoring method was performed to evaluate the neurological function of rats. TTC staining was performed to measure the volume of cerebral infarction. HE and TUNEL staining were used to observe brain tissue lesions and cell apoptosis in rats. ELISA was used to detect the inflammatory factors interleukin (IL)-1β, tumor necrosis factor-α (TNF-α), and IL-6 in rat brain homogenates. Western blot was performed to detect the CaMKK2 and AMPK related proteins. Results: For the normal group, the cerebral infarction group showed improved neurological function scores, cerebral infarction, increased cell apoptosis rate, IL-1β, TNF-α, IL-6, and decreased p-CaMKK2 and p-AMPK (P<0.05). For the cerebral infarction group, the L-xanthohumol group and H-xanthohumol group showed decreased neurological function scores, reduced cerebral infarction volume, reduced brain tissue damage, decreased cell apoptosis rate, IL-1β, TNF-α, IL-6, and increased p-CaMKK2 and p-AMPK (P<0.05), and the therapeutic effect of H-xanthohumol was better than that of L-xanthohumol (P<0.05). The CaMKK2 inhibitor STO-609 eliminated the inhibitory effects of xanthohumol on neuronal apoptosis and inflammatory response in rats with acute cerebral infarction (P<0.05). Conclusion: Xanthohumol may alleviate neuronal apoptosis and inflammatory response in rats with acute cerebral infarction by activating CaMKK2/AMPK signaling pathway.

Key words： Acute cerebral infarction Xanthohumol Neuronal apoptosis CaMKK2/AMPK signaling pathway

基金资助:黑龙江省卫生健康委员会科研项目,(编号:2020021)

通讯作者: 刘照寒

引用本文:

常亮, 李明, 李晶, 刘照寒. 黄腐酚调节CaMKK2/AMPK信号通路对急性脑梗死大鼠神经元凋亡及炎症反应的影响[J]. 河北医学, 2025, 31(12): 1963-1969.
CHANG Liang, LI Ming, LI Jing, et al. Effects of Xanthohumol on Neuronal Apoptosis and Inflammatory Response in Rats with Acute Cerebral Infarction by Regulating CaMKK2/AMPK Signaling Pathway. HeBei Med, 2025, 31(12): 1963-1969.

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http://www.hbyxzzs.cn/CN/10.3969/j.issn.1006-6233.2025.12.05 或 http://www.hbyxzzs.cn/CN/Y2025/V31/I12/1963

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