首页> 外文期刊>American Journal of Physiology >Regression of cholangiocyte proliferation after cessation of ANIT feeding is coupled with increased apoptosis.
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Regression of cholangiocyte proliferation after cessation of ANIT feeding is coupled with increased apoptosis.

机译:停止ANIT喂养后胆管细胞增殖的退化与凋亡增加有关。

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摘要

Cholangiocyte proliferation and loss through apoptosis occur in cholestatic liver diseases. Our aim was to determine the mechanisms of apoptosis in an animal model of ductal hyperplasia. Rats were fed alpha-naphthylisothiocyanate (ANIT) for 2 wk and subsequently fed normal chow for 1, 2, and 4 wk. Proliferation was assessed in sections by morphometry and in small and large cholangiocytes by proliferating cellular nuclear antigen immunoblots and measurement of cAMP levels. Apoptosis and reactive oxygen species (ROS) levels were also assessed. ANIT feeding increased small and large cholangiocyte proliferation and apoptosis. Cessation of ANIT feeding was associated with decreased proliferation and a further increase in apoptosis in small and large cholangiocytes. Cholangiocytes from ANIT-fed rats or exposed to ANIT in vitro showed increased apoptosis and ROS generation. ANIT-induced duct injury results in enhanced proliferation and apoptosis in small and large cholangiocytes. The mechanism of ANIT-inducedapoptosis may be due to ROS generation induced directly by ANIT. Our model has implications for understanding the pathophysiology of cholangiopathies (characterized by the coexistence of cholangiocyte apoptosis and proliferation).
机译:在胆汁淤积性肝病中发生胆管细胞增殖和通过凋亡的损失。我们的目的是确定导管增生动物模型中细胞凋亡的机制。给大鼠喂食2周的α-萘基异硫氰酸萘酯(ANIT),然后喂食1周,2周和4周的普通食物。通过形态测量来评估切片中的增殖,并通过增殖细胞核抗原免疫印迹和测量cAMP水平来评估大小胆管细胞中的增殖。还评估了细胞凋亡和活性氧(ROS)水平。 ANIT喂养可增加大小胆管细胞的增殖和凋亡。停止喂食ANIT与大小胆管细胞的增殖减少和凋亡的进一步增加有关。来自ANIT喂养的大鼠或在体外暴露于ANIT的胆管细胞显示出增加的凋亡和ROS生成。 ANIT诱导的导管损伤导致大小胆管细胞的增殖和凋亡增强。 ANIT诱导凋亡的机制可能是由于ANIT直接诱导产生ROS。我们的模型对理解胆管病的病理生理学具有影响(以胆管细胞凋亡和增殖的共存为特征)。

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