摘要
背景:短链脂肪酸丁酸(BT)是首选的结肠细胞能源。尚未完全阐明BT对仔猪小肠上皮细胞的分化,增殖和凋亡的影响及其潜在机制。 方法:在这项研究中,发现0.2-0.4 mM BT促进了前列腺空肠上皮(IPEC-J2)细胞的分化。 0.5 mM或更高浓度的BT以剂量和时间依赖性方式显着损害细胞活力。此外,高浓度的BT抑制IPEC-J2细胞增殖并诱导G2 / M期细胞周期停滞。 结果:我们的结果表明,BT通过caspase8-caspase3途径触发IPEC-J2细胞凋亡,并伴有过量的活性氧(ROS)和TNF-α的产生。高浓度的BT抑制了与溶酶体形成增加有关的细胞自噬。已发现,p38 MAPK抑制剂SB202190可减弱BT降低的IPEC-J2细胞活力。此外,SB202190减弱了负责正常酸性溶酶体的BT增加的p38 MAPK靶标DDIT3 mRNA水平和V-ATPase mRNA水平。 结论:总而言之,1)BT在0.2-0.4 mM时促进IPEC-J2细胞的分化; 2)0.5 mM或更高浓度的BT通过p38 MAPK途径诱导细胞凋亡; 3)BT抑制细胞自噬并在高浓度下促进溶酶体形成。
关键词: 丁酸,p38 MAPK,凋亡,自噬,V-ATPase,溶酶体。
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