Cytoprotective effects of taurocholic acid feeding on the biliary tree after adrenergic denervation of the liver.
Cytoprotective effects of taurocholic acid feeding on the biliary tree after adrenergic denervation of the liver.
复制标题
肝脏肾上腺素去神经支配后牛磺胆酸对胆管树的细胞保护作用。
DOI：
10.1111/j.1478-3231.2007.01443.x
复制
发表时间：
2007
期刊：
影响因子：
--
通讯作者：
Alpini,Gianfranco
中科院分区：
文献类型：
--
作者：
Marzioni,Marco;Ueno,Yoshiyuki;Glaser,Shannon;Francis,Heather;Benedetti,Antonio;Alvaro,Domenico;Venter,Juliet;Fava,Giammarco;Alpini,Gianfranco
背景：胆管病损害胆管细胞增殖和凋亡之间的平衡，导致胆管消失和肝功能衰竭。牛磺胆酸 (TC) 对于胆管细胞增殖和对胆汁淤积的功能反应至关重要。胆汁酸和神经递质协同调节胆管上皮对胆汁淤积的生物反应。胆汁淤积过程中肝脏去肾上腺素能导致胆管损伤。目的：验证TC喂养是否可以预防胆汁淤积过程中肾上腺素能去神经引起的胆管树损伤。方法：对接受胆管结扎（BDL）和肾上腺素去神经的大鼠喂食富含TC的饮食，每天不给予或存在TC磷脂酰肌醇3激酶（PI3K）抑制剂渥曼青霉素治疗1周。结果：TC可阻止肾上腺素能去神经诱导的胆管细胞凋亡。 TC 还可以恢复胆管细胞的增殖和功能活性，而肾上腺素去神经支配后胆管细胞的增殖和功能活性会降低。 TC 阻止肾上腺素去神经诱导的 AKT 去磷酸化。同时给予渥曼青霉素可消除TC的细胞保护作用。总结/结论：TC给药可预防肝脏去肾上腺素神经引起的胆管树损伤。这些新发现为理解胆汁酸的潜力，特别是在移植后肝病中的潜力开辟了新的视角。
Background:Cholangiopathies impair the balance between proliferation and apoptosis of cholangiocytes leading to the disappearance of bile ducts and liver failure. Taurocholic acid (TC) is essential for cholangiocyte proliferative and functional response to cholestasis. Bile acids and neurotransmitters co‐operatively regulate the biological response of the biliary epithelium to cholestasis. Adrenergic denervation of the liver during cholestasis results in the damage of bile ducts.Aim:To verify whether TC feeding prevents the damage of the biliary tree induced by adrenergic denervation in the course of cholestasis.Methods:Rats subjected to bile duct ligation (BDL) and to adrenergic denervation were fed a TC‐enriched diet, in the absence or presence of daily administration of the phosphatidyl‐inositol‐3‐kinase (PI3K) inhibitor wortmannin for 1 week.Results:TC prevented the induction of cholangiocyte apoptosis induced by adrenergic denervation. TC also restored cholangiocyte proliferation and functional activity, reduced after adrenergic denervation. TC prevented AKT dephosphorylation induced by adrenergic denervation. The cytoprotective effects of TC were abolished by the simultaneous administration of wortmannin.Summary/conclusions:TC administration prevents the damage of the biliary tree induced by the adrenergic denervation of the liver. These novel findings open novel perspectives in the understanding of the potential of bile acids especially in post‐transplant liver disease.