School of Public Health, and CHIRI Biosciences Research Precinct, Faculty of Health Sciences, Curtin University, Bentley, GPO Box U1987, Perth 6845, WA, Australia.
Lipids Health Dis. 2014 Jun 3;13:91. doi: 10.1186/1476-511X-13-91.
Probucol has been shown to prevent cerebral capillary disturbances characterized by blood-to-brain extravasation of plasma derived proteins and neurovascular inflammation in mice maintained on western-styled diets for 12 weeks. However the effect of probucol on capillary integrity in aging models with capillary dysfunction is not known.
Wild-type C57BL6 mice were randomized to a low-fat (LF); saturated-fat (SFA); or SFA + Probucol diet for up to12 months of intervention.
Mice fed the LF diet had substantially greater parenchymal abundance of plasma derived IgG and apo B lipoproteins at 12 months, compared to LF mice at 3 months of intervention. Markers of neurovascular inflammation were also greater at 12 months in LF fed mice compared to LF mice at 3 months. The SFA diet exacerbated the aging induced parenchymal abundance of IgG and of apo B lipoproteins and neurovascular inflammation at 12 months. The SFA effects were associated with increased production of intestinal lipoprotein amyloid-β (Aβ). The co-provision of probucol with the SFA completely abolished heightened inflammation at 12 months. Probucol attenuated SFA-induced capillary permeability but had only a modest inhibitory effect on parenchymal retention of apoB lipoproteins. The improvements in markers of inflammation and capillary integrity because of probucol correlated with enterocytic genesis of chylomicron Aβ.
In this long-term feeding study, probucol profoundly suppressed dietary SFA induced disturbances in capillary integrity but had a more modest effect on age-associated changes.
在接受西式饮食 12 周的小鼠中，普罗布考已被证明可预防以血脑屏障外渗的血浆源性蛋白和神经血管炎症为特征的脑毛细血管紊乱。然而，普罗布考对伴有毛细血管功能障碍的衰老模型中的毛细血管完整性的影响尚不清楚。
将野生型 C57BL6 小鼠随机分为低脂（LF）、饱和脂肪（SFA）或 SFA+普罗布考饮食，干预时间长达 12 个月。
与 3 个月时的 LF 组相比，12 个月时，给予 LF 饮食的小鼠实质内血浆源性 IgG 和载脂蛋白 B 脂蛋白的含量明显增加。与 3 个月时的 LF 组相比，12 个月时 LF 喂养组的神经血管炎症标志物也更高。SFA 饮食加剧了 12 个月时衰老诱导的 IgG 和载脂蛋白 B 脂蛋白实质内含量增加以及神经血管炎症。SFA 的作用与肠脂蛋白淀粉样β（Aβ）的产生增加有关。与 SFA 同时提供普罗布考可完全消除 12 个月时的炎症加剧。普罗布考可减轻 SFA 诱导的毛细血管通透性增加，但对载脂蛋白 B 脂蛋白实质内保留仅有适度的抑制作用。由于普罗布考，炎症和毛细血管完整性标志物的改善与乳糜微粒 Aβ的肠上皮细胞发生有关。
在这项长期喂养研究中，普罗布考可显著抑制饮食 SFA 诱导的毛细血管完整性紊乱，但对与年龄相关的变化的影响较小。
