Acute carbon tetrachloride feeding induces damage of large but not small cholangiocytes from BDL rat liver
Acute carbon tetrachloride feeding induces damage of large but not small cholangiocytes from BDL rat liver
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DOI：
10.1152/ajpgi.1999.276.5.g1289
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发表时间：
1999-05-01
影响因子：
4.5
通讯作者：
Alpini, G
中科院分区：
文献类型：
--
作者：
LeSage, GD;Glaser, SS;Alpini, G
胆管损伤和/或损失仅限于胆管疾病中的一系列管道尺寸。我们检验了CCl 4只损害大导管的假设。四氯化碳或矿物油给予胆管结扎（BDL）大鼠，和1，2，和7天后，小和大胆管细胞进行纯化和评估的凋亡，增殖和分泌。在原位，我们通过形态计量学和TUNEL分析测量细胞凋亡，并通过形态计量学测量小导管和大导管的数量。CCl 4给药后两天，我们发现小导管的数量增加，大导管的数量减少。体外仅在大胆管细胞中观察到细胞凋亡，并且伴有大胆管细胞增殖和分泌的丧失以及胰泌素利胆作用的丧失。新生小胆管细胞表达促胰液素受体基因和促胰液素诱导的cAMP反应。与大胆管损伤一致，我们仅在大胆管细胞中检测到细胞色素P-4502 E1（CCl 4将其转化为自由基）。CCl 4诱导与大胆管细胞增殖和分泌丧失相关的大胆管选择性凋亡。
Bile duct damage and/or loss is limited to a range of duct sizes in cholangiopathies. We tested the hypothesis that CCl4 damages only large ducts. CCl4 or mineral oil was given to bile duct-ligated (BDL) rats, and 1, 2, and 7 days later small and large cholangiocytes were purified and evaluated for apoptosis, proliferation, and secretion. In situ, we measured apoptosis by morphometric and TUNEL analysis and the number of small and large ducts by morphometry Two days after CCl4 administration, we found an increased number of small ducts and reduced number of large ducts. In vitro apoptosis was observed only in large cholangiocytes, and this was accompanied by loss of proliferation and secretion in large cholangiocytes and loss of choleretic effect of secretin. Small cholangiocytes de novo express the secretin receptor gene and secretin-induced cAMP response. Consistent with damage of large ducts, we detected cytochrome P-4502E1 (which CCl4 converts to its radicals) only in large cholangiocytes. CCl4 induces selective apoptosis of large ducts associated with loss of large cholangiocyte proliferation and secretion.