Peroxisome proliferators-activated alpha agonist treatment ameliorates hepatic damage in rats with obstructive jaundice:: an experimental study
Peroxisome proliferators-activated alpha agonist treatment ameliorates hepatic damage in rats with obstructive jaundice:: an experimental study
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DOI：
10.1186/1471-230x-7-44
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发表时间：
2007-11-28
影响因子：
2.4
通讯作者：
Uenal, Selahattin
中科院分区：
文献类型：
--
作者：
Cindoruk, Mehmet;Kerem, Mustafa;Uenal, Selahattin
背景资料：过氧化物酶体增殖物激活受体α（PPAR α）激活调节胆固醇代谢并抑制胆汁酸合成。本研究旨在评价短期给予非诺贝特（一种过氧化物酶体增殖物激活受体α激动剂）对胆汁淤积症中促炎细胞因子、细胞凋亡和肝细胞损伤的影响。I =假手术，II =胆管结扎（BDL），III = BDL +溶剂（阿拉伯树胶），IV = BDL +非诺贝特（100 mg/ kg/天）。所有大鼠于第7天处死，取血和肝组织。评价血清中的总胆红素、转氨酶（AST）、丙氨酸转氨酶（ALT）和碱性磷酸酶（ALP）、γ-谷氨酰转移酶（GGT）、肿瘤坏死因子α（TNF-α）、白细胞介素1 β（IL-1 β）和总胆汁酸（TBA）以及肝损伤评分;肝组织中的门静脉炎症、坏死、胆管数量。结果：非诺贝特组血清总胆红素、AST、ALT、ALP、GGT、TNF-α、IL-1 β、TBA水平均显著降低（P < 0.01）。BDL组大鼠肝门部炎症、肝组织坏死、胆管数目及细胞凋亡均明显高于假手术组（P < 0.01）。结果：非诺贝特能显著增加BDL大鼠肝组织中胆管数目（P <0.01），但不能显著增加胆管数目（P < 0.01）。结论：短期给予非诺贝特对BDL大鼠肝细胞损伤和凋亡有保护作用。
Background: Peroxisome proliferators-activated receptor alpha ( PPAR alpha) activation modulates cholesterol metabolism and suppresses bile acid synthesis. This study aims to evaluate the effect of short-term administration of fenofibrate, a PPAR alpha agonist, on proinflammatory cytokines, apoptosis, and hepatocellular damage in cholestasis.Methods: Forty male Wistar rats were randomly divided into four groups: I = sham operated, II = bile duct ligation ( BDL), III = BDL + vehicle ( gum Arabic), IV = BDL + fenofibrate ( 100 mg/ kg/ day). All rats were sacrificed on 7(th) day after obtaining blood samples and liver tissue. Total bilirubin, aminotransferase ( AST), alanine aminotransferase ( ALT) and alkaline phosphatase ( ALP), gamma-glutamyl transferase, ( GGT), tumor necrosis factor alpha ( TNF-alpha), interleukin 1 beta ( IL-I beta), and total bile acid ( TBA) in serum, and liver damage scores; portal inflammation, necrosis, bile duct number, in liver tissue were evaluated. Apoptosis in liver was also assessed by immunohistochemical staining.Results: Fenofibrate administration significantly reduced serum total bilirubin, AST, ALT, ALP, and GGT, TNF-alpha, IL-I beta levels, and TBA ( P < 0.01). Hepatic portal inflammation, hepatic necrosis, number of the bile ducts and apoptosis in rats with BDL were more prominent than the sham-operated animals ( P < 0.01). PPAR alpha induction improved all histopathologic parameters ( P < 0.01), except for the number of the bile duct, which was markedly increased by fenofibrate therapy ( P < 0.01).Conclusion: Short-term administration of fenofibrate to the BDL rats exerts beneficial effects on hepatocellular damage and apoptosis.