Marzioni Marco, Ueno Yoshiyuki, Glaser Shannon, Francis Heather, Benedetti Antonio, Alvaro Domenico, Venter Juliet, Fava Giammarco, Alpini Gianfranco
Department of Gastroenterology, Università Politecnica delle Marche, Ancona, Italy.
Liver Int. 2007 May;27(4):558-68. doi: 10.1111/j.1478-3231.2007.01443.x.
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.
To verify whether TC feeding prevents the damage of the biliary tree induced by adrenergic denervation in the course of cholestasis.
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.
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.
胆管疾病破坏胆管细胞增殖与凋亡之间的平衡，导致胆管消失和肝衰竭。牛磺胆酸（TC）对于胆管细胞对胆汁淤积的增殖和功能反应至关重要。胆汁酸和神经递质协同调节胆管上皮对胆汁淤积的生物学反应。胆汁淤积期间肝脏的肾上腺素能去神经支配会导致胆管损伤。
验证给予TC是否能预防胆汁淤积过程中肾上腺素能去神经支配所致的胆管树损伤。
对接受胆管结扎（BDL）和肾上腺素能去神经支配的大鼠，在给予或不给予每日磷脂酰肌醇-3-激酶（PI3K）抑制剂渥曼青霉素的情况下，给予富含TC的饮食1周。
TC可预防肾上腺素能去神经支配诱导的胆管细胞凋亡。TC还可恢复肾上腺素能去神经支配后降低的胆管细胞增殖和功能活性。TC可预防肾上腺素能去神经支配诱导的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：给予TC可预防肝脏肾上腺素能去神经支配所致的胆管树损伤。这些新发现为理解胆汁酸的潜在作用，尤其是在移植后肝病中的作用，开辟了新的视角。
