Karakan Tarkan, Kerem Mustafa, Cindoruk Mehmet, Engin Doruk, Alper Murat, Akın Okan
Department of Gastroenterology, Gazi University, School of Medicine, Ankara, Turkey.
Turk J Gastroenterol. 2013;24(2):134-40. doi: 10.4318/tjg.2013.0605.
BACKGROUND/AIMS: Peroxisome proliferators-activated receptor alpha activation modulates cholesterol metabolism and suppresses bile acid synthesis. The trefoil factor family comprises mucin-associated proteins that increase the viscosity of mucins and help protect epithelial linings from insults. We evaluated the effect of short-term administration of fenofibrate, a peroxisome proliferators activated receptor alpha agonist, on trefoil factor family-3 expression, degree of apoptosis, generation of free radicals, and levels of proinflammatory cytokines in the liver tissue of bile duct-ligated rats.
Forty male Wistar rats were randomly divided into four groups: 1 = sham operated, 2 = bile duct ligation, 3 = bile duct-ligated + vehicle (gum Arabic), and 4 = bile duct-ligated + fenofibrate (100 mg/kg/day). All rats were sacrificed on the 7 th day after obtaining blood samples and liver tissue. Liver function tests, tumor necrosis factor-alpha and interleukin 1 beta in serum, and trefoil factor family-3 mRNA expression, degree of apoptosis (TUNEL) and tissue malondialdehyde (malondialdehyde, end-product of lipid peroxidation by reactive oxygen species) in liver tissue were evaluated.
Fenofibrate administration significantly reduced serum total bilirubin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma-glutamyl transferase, and tumor necrosis factor-alpha and interleukin-1β levels. Apoptosis and malondialdehyde were significantly reduced in the fenofibrate group. Trefoil factor family-3 expression increased with fenofibrate treatment in bile duct-ligated rats.
The peroxisome proliferators-activated receptor alpha agonist fenofibrate significantly increased trefoil factor family-3 expression and decreased apoptosis and lipid peroxidation in the liver and attenuated serum levels of proinflammatory cytokines in bile duct-ligated rats. Further studies are needed to determine the protective role of fenofibrate in human cholestatic disorders.
背景/目的：过氧化物酶体增殖物激活受体α激活可调节胆固醇代谢并抑制胆汁酸合成。三叶因子家族由与粘蛋白相关的蛋白质组成，这些蛋白质可增加粘蛋白的粘度，并有助于保护上皮衬里免受损伤。我们评估了短期给予非诺贝特（一种过氧化物酶体增殖物激活受体α激动剂）对胆管结扎大鼠肝组织中三叶因子家族3表达、凋亡程度、自由基生成以及促炎细胞因子水平的影响。
40只雄性Wistar大鼠随机分为四组：1组 = 假手术组，2组 = 胆管结扎组，3组 = 胆管结扎 + 赋形剂（阿拉伯胶）组，4组 = 胆管结扎 + 非诺贝特（100 mg/kg/天）组。在采集血样和肝组织后的第7天处死所有大鼠。评估肝功能测试、血清中的肿瘤坏死因子-α和白细胞介素1β，以及肝组织中的三叶因子家族3 mRNA表达、凋亡程度（TUNEL法）和组织丙二醛（丙二醛，活性氧脂质过氧化的终产物）。
给予非诺贝特可显著降低血清总胆红素、天冬氨酸转氨酶、丙氨酸转氨酶、碱性磷酸酶、γ-谷氨酰转移酶以及肿瘤坏死因子-α和白细胞介素-1β水平。非诺贝特组的凋亡和丙二醛显著减少。在胆管结扎大鼠中，非诺贝特治疗使三叶因子家族3表达增加。
过氧化物酶体增殖物激活受体α激动剂非诺贝特可显著增加胆管结扎大鼠肝组织中三叶因子家族3的表达，减少凋亡和脂质过氧化，并降低血清促炎细胞因子水平。需要进一步研究以确定非诺贝特在人类胆汁淤积性疾病中的保护作用。
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