Cholinergic system modulates growth, apoptosis, and secretion of cholangiocytes from bile duct-ligated rats
Cholinergic system modulates growth, apoptosis, and secretion of cholangiocytes from bile duct-ligated rats
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DOI：
10.1016/s0016-5085(99)70567-6
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发表时间：
1999-07-01
期刊：
影响因子：
29.4
通讯作者：
Alpini, G
中科院分区：
文献类型：
--
作者：
LeSage, G;Alvaro, D;Alpini, G
背景和目标：为了探讨胆碱能系统在调节胆管细胞功能中的作用，我们评估了迷走神经切断术对胆管结扎大鼠（BDL大鼠）胆管细胞增殖和分泌的影响。方法：胆管结扎（BDL）后，切除迷走神经，7 d后测定M3受体表达。通过形态计量学和DNA合成测量来评估胆管细胞增殖。通过光学显微镜和Annexin-V染色评价细胞凋亡。通过测量促胰液素诱导的胆汁分泌、促胰液素受体（SR）基因表达和环腺苷酸（cAMP）水平来评价导管分泌。结果：迷走神经切断后，胆管细胞M3受体表达减少。迷走神经切断可使胆管DNA合成和胆管质量明显减少，而胆管细胞凋亡增加。迷走神经切断术减少了导管分泌物。毛喉素治疗阻止了BDL大鼠迷走神经切断术引起的cAMP水平下降，维持了胆管细胞增殖，并减少了迷走神经切断术引起的胆管细胞凋亡。毛喉素也维持胆管细胞分泌。结论：迷走神经切断术损害胆管细胞增殖，促进细胞凋亡，导致胆管质量减少对BDL的反应。胰泌素诱导的胆汁分泌BDL大鼠几乎消除迷走神经切断术与降低胆管细胞cAMP水平。通过给予毛喉素维持cAMP水平可以防止迷走神经切断术对胆管细胞增殖、细胞凋亡和分泌的影响。
Background & Aims: To investigate the role of the cholinergic system in regulation of cholangiocyte functions, we evaluated the effects of vagotomy on cholangiocyte proliferation and secretion in rats that underwent bile duct ligation (BDL rats). Methods: After bile duct ligation (BDL), the vagus nerve was resected; 7 days later, expression of M3 acetylcholine receptor was evaluated. Cholangiocyte proliferation was assessed by morphometry and measurement of DNA synthesis. Apoptosis was evaluated by light microscopy and annexin-V staining. Ductal secretion was evaluated by measurement of secretin-induced choleresis, secretin receptor (SR) gene expression, and cyclic adenosine 3',5'-monophosphate (cAMP) levels. Results: Vagotomy decreased the expression of M3 acetylcholine receptors in cholangiocytes. DNA synthesis and ductal mass were markedly decreased, whereas cholangiocyte apoptosis was increased by vagotomy. Vagotomy decreased ductal secretion. Forskolin treatment prevented the decrease in cAMP levels induced by vagotomy, maintained cholangiocyte proliferation, and decreased cholangiocyte apoptosis caused by vagotomy in BDL rats. Cholangiocyte secretion was also maintained by forskolin. Conclusions: Vagotomy impairs cholangiocyte proliferation and enhances apoptosis, leading to decreased ductal mass in response to BDL. Secretin-induced choleresis of BDL rats was virtually eliminated by vagotomy in association with decreased cholangiocyte cAMP levels. Maintenance of cAMP levels by forskolin administration prevents the effects of vagotomy on cholangiocyte proliferation, apoptosis, and secretion.