燕麦纤维对LDLR^(-/-)小鼠大脑Aβ和Tau蛋白的影响

EFFECTS OF OAT FIBER ON Aβ AND TAU PROTEINS OF THE BRAIN IN LDLR^(-/-) MICE

目的 探讨燕麦纤维对LDLR^(-/-)小鼠大脑皮质和海马中β-淀粉样蛋白(Aβ)及磷酸化Tau蛋白的影响及可能机制。方法 20只6w龄雄性LDLR^(-/-)小鼠按体重随机分为动脉粥样硬化模型组(AS)和燕麦纤维组(OF),预防性干预14w。实验结束后,收集小鼠主动脉、大脑皮质和海马组织;采用油红O染色观察主动脉病理改变;采用Western blot检测大脑皮质和海马中Aβ1-42、丝氨酸396位点和404位点的磷酸化Tau蛋白(p-Tau ser396和p-Tau ser404)及G蛋白偶联受体41(GPR41)、GPR43和GPR109A的蛋白表达水平。结果 油红O染色显示,燕麦纤维干预显著减少了LDLR^(-/-)小鼠主动脉粥样斑块面积(P<0.05)。与AS组相比,燕麦纤维对LDLR^(-/-)小鼠大脑皮质中Aβ1-42、p-Tau ser396、p-Tauser404的蛋白表达水平无明显影响(P>0.05),但显著降低了海马中Aβ1-42和p-Tauser396的蛋白表达水平(P<0.05);同时,燕麦纤维显著上调了LDLR^(-/-)小鼠大脑皮质和海马中GPR43及大脑皮质中GPR109A的蛋白表达水平(P<0.05)。结论 燕麦纤维可改善动脉粥样硬化,同时可能通过激活GPRs降低LDLR^(-/-)小鼠海马Aβ1-42的表达水平和Tau蛋白的磷酸化水平,改善大脑神经病理改变导致的神经毒性作用,发挥抗AS和神经保护的作用。[营养学报,2022,44(1):35-39]

Objective To investigate the effects of oat fiber on amyloid-β(Aβ) and phosphorylated Tau proteins in the cerebral cortex and hippocampus of LDLR;mice and the possible mechanisms. Methods Twenty 6-week-old male LDLR;mice were randomly divided into the atherosclerosis model(AS) group and oat fiber(OF) group according to their weight and a 14 weeks preventive intervention was conducted. At the end of the experiment, the aorta, cerebral cortex and hippocampus of the mice were collected. The aorta was taken for oil red O staining to observe the pathological lesions. Western blot analysis was used to detect the protein expressions of Aβ1-42, phosphorylated Tau protein at serine 396(p-Tau ser396) and serine 404(p-Tau ser404) and G protein coupled receptors including GPR41, GPR43 and GPR109A in the cortex and hippocampus. Results Oil red O staining showed that oat fiber significantly reduced the area of aortic atheromatous plaques in LDLR;AS mice(P<0.05). Compared with the AS group, oat fiber had no significant effect on Aβ1-42,p-Tau ser396 or p-Tau ser404 expression in the cerebral cortex of LDLR;AS mice(P>0.05), but it significantly reduced the protein expressions of Aβ1-42 and p-Tau ser396 in the hippocampus(P<0.05). Also, oat fiber significantly reduced the protein expression of GPR43 in the cerebral cortex and hippocampus and GPR109A in the cerebral cortex of LDLR;AS mice(P<0.05). Conclusion Besides ameliorating atherosclerosis, oat fiber might improve the neurotoxic effects caused by neuropathic alterations in the brain by activating GPRs to reduce the protein expression of Aβ1-42 and the phosphorylation of Tau protein in the hippocampus of LDLR;mice, thus contributing to anti-atherosclerosis and neuroprotection. [ACTA NUTRIMENTA SINICA, 2022, 44(1):35-39]