Alisol B 23-乙酸盐通过LXRα/ ACAT2途径激活空肠中的ABCG5 / G8，以减轻卵巢切除的ApoE <sup>-/-</sup>小鼠的动脉粥样硬化,Aging-US

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Alisol B 23-乙酸盐通过LXRα/ ACAT2途径激活空肠中的ABCG5 / G8，以减轻卵巢切除的ApoE ^-/-小鼠的动脉粥样硬化
Aging-US ( IF 3.9 ) Pub Date : 2020-11-25 , DOI: 10.18632/aging.104185
Xi-Chao Yu ₁ , Yu Fu ₁ , Yun-Hui Bi ₁ , Wei-Wei Zhang ₁ , Jun Li ₁ , Tingting Ji ₁ , Ying Chao ₁ , Qing-Hai Meng ₁ , Qi Chen ₁ , Meng-Hua Ma ₁ , Yu-Han Zhang ₁ , Jinjun Shan _{2,

3} , Hui-Min Bian _{1,

4,

5,

6}

Affiliation

植物甾醇已显示可改善血脂水平并治疗动脉粥样硬化。这项研究调查了植物甾醇Alisol B 23-乙酸酯（AB23A）对空肠脂质代谢和动脉粥样硬化的影响。结果表明，在腹腔内施用AB23A可以显着减少去卵巢ApoE ^-/-空肠中的动脉粥样硬化斑块面积和脂质蓄积喂高脂饮食的小鼠，还可以改善血浆和空肠的脂质质谱。体外研究表明，AB23A可以增加暴露于高脂肪浓度的Caco-2细胞中的胆固醇流出，并增加ATP结合盒转移蛋白G5 / G8（ABCG5 / G8），肝脏X受体α（LXRα）的表达。此外，抑制LXRα可以显着消除AB23A对减少细胞内脂质蓄积的活性作用。我们还证实了AB23A对高浓度脂肪培养的Caco-2细胞中的酰基辅酶A胆固醇酰基转移酶2（ACAT2）具有负面影响，并且我们发现AB23A进一步降低了用ACAT2抑制剂吡啶并戊二烯或ACAT2抑制剂处理的细胞中ACAT2的表达。用ACAT2 siRNA转染。结论，

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Alisol B 23-acetate activates ABCG5/G8 in the jejunum via the LXRα/ACAT2 pathway to relieve atherosclerosis in ovariectomized ApoE-/- mice

Phytosterols have been shown to improve blood lipid levels and treat atherosclerosis. This research investigated the effects of phytosterol Alisol B 23-acetate (AB23A) on jejunum lipid metabolism and atherosclerosis. The results show that intragastric administration of AB23A can significantly reduce atherosclerotic plaque area and lipid accumulation in the jejunum of ovariectomized ApoE^-/- mice fed a high-fat diet and can also improve the lipid mass spectra of the plasma and jejunum. In vitro studies have shown that AB23A can increase cholesterol outflow in Caco-2 cells exposed to high fat concentrations and increase the expression of ATP-binding cassette transfer proteins G5/G8 (ABCG5/G8), the liver X receptor α (LXRα). Furthermore, inhibition of LXRα can significantly eliminate the active effect of AB23A on decreasing intracellular lipid accumulation. We also confirmed that AB23A has a negative effect on Acyl-CoA cholesterol acyltransferase 2 (ACAT2) in Caco-2 cells cultured in the high concentrations of fat, and we found that AB23A further reduces ACAT2 expression in cells treated with the ACAT2 inhibitor pyripyropene or transfected with ACAT2 siRNA. In conclusion, we confirmed that AB23A can reduce the absorption of dietary lipids in the jejunum by affecting the LXRα-ACAT2-ABCG5/G8 pathway and ultimately exert an anti-atherosclerotic effect.

更新日期：2021-01-01

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