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目的:神经炎症作为阿尔茨海默氏病(Alzheimer’s disease,AD)的主要病理机制之一,主要表现为小胶质细胞激活和炎症因子环氧合酶-2(cyclooxygenase-2,COX-2)的过表达,最终导致神经元损伤和记忆障碍。本研究主要探讨反式桂皮醛(transcinnamaldehyde,TCA)对AD神经炎症过程中小胶质细胞激活和COX-2过表达的抑制作用及其机制。方法:利用脂多糖(lipopolysaccharides,LPS)诱导建立AD的细胞和动物神经炎症模型;采用qRT-PCR和Western blot检测小胶质细胞和小鼠皮质COX-2mRNA和蛋白表达,免疫组化方法观察皮质小胶质细胞形态变化。结果:脂多糖激活原代小胶质细胞后COX-2 mRNA和蛋白表达均明显增多,桂皮醛(10μM)通过降低COX-2 mRNA稳定性抑制小胶质细胞COX-2 mRNA和蛋白的过表达;同时桂皮醛(50 mg/kg)对脂多糖诱导神经炎症小鼠的皮质COX-2 mRNA和蛋白过表达也有抑制作用,并对皮质小胶质细胞形态改变有明显的恢复作用。结论:桂皮醛抑制AD神经炎症的小胶质细胞激活可能是通过降低COX-2过表达发挥作用的。
OBJECTIVE: Neuroinflammation is one of the major pathological mechanisms of Alzheimer’s disease (AD). It mainly displays microglial activation and cyclooxygenase-2 (COX-2) Overexpression, eventually leading to neuronal damage and memory impairment. This study mainly investigated the inhibitory effect of transcinnamaldehyde (TCA) on the activation of microglia and the overexpression of COX-2 during AD neuroinflammation and its mechanism. Methods: Neuronal inflammation models of AD cells and animals were induced by lipopolysaccharides (LPS). COX-2 mRNA and protein expression in microglia and mouse cortex were detected by qRT-PCR and Western blot. Cortical samples were examined by immunohistochemistry Microglia morphological changes. Results: The expressions of COX-2 mRNA and protein in primary microglial cells were significantly increased after lipopolysaccharide stimulation. Cinnamic aldehyde (10μM) inhibited the COX-2 mRNA and protein overexpression in microglia cells by decreasing the stability of COX-2 mRNA ; While Cinnamaldehyde (50 mg / kg) also inhibited COX-2 mRNA and protein cortical expression in cortical neurons induced by lipopolysaccharide in mice and significantly restored the morphological changes of cortical microglial cells. CONCLUSION: Cinnamaldehyde inhibits microglial activation of AD neuroinflammation may play a role by reducing COX-2 overexpression.