南方医科大学学报

南方医科大学学报 ›› 2014, Vol. 34 ›› Issue (05): 731-.

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降脂药普罗布考改善NASH大鼠肝脏脂肪变性的机制

吴蓉，吴小翎，刘波，张伟，高静，肖晓秋，张霞   

  • 出版日期:2014-05-20 发布日期:2014-05-20

Effect of probucol in improving hepatic steatosis in rats with non-alcoholic
steatohepatitis and the mechanism

  • Online:2014-05-20 Published:2014-05-20

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摘要： 目的探讨降脂药物普罗布考对非酒精性脂肪性肝炎大鼠肝脏病理、血清学指标的改善作用、对肝脏胆汁酸受体FXR及下
游基因、蛋白SHP、SREBP-1C表达的影响。方法雄性SD大鼠40只，随机平均分4组：（1）正常对照组，予普通饲料；（2）高脂组，
予高脂饲料；（3）普罗布考对照组，予普通饲料及普罗布考灌胃（500 mg/kg·d-1）；（4）普罗布考干预组，予高脂饲料及普罗布考灌
胃（500 mg/kg·d-1）。15周后处死，检测各组大鼠血清转氨酶、血脂、胆汁酸，同时取肝组织，切片行HE染色及病理评分；RT- PCR
及Western Blot的方法检测肝组织FXR、SHP及SREBP-1C基因及蛋白的表达水平。结果与高脂组比较，普罗布考干预组肝脏
脂肪变性及炎症浸润程度明显减轻，血清ALT（126.40±52.56 vs 80.18±22.90 U/L，P<0.01）、AST（250.40±30.45 vs 179.45±41.14
U/L，P<0.01）及胆固醇（2.7±0.2 vs 2.4±0.3 mmol/L，P<0.01）、游离脂肪酸（0.734±.0.11 vs 0.557±0.19 mmol/L，P<0.05），胆汁酸
（48.3±11.6 vs 24.9±17.7 μmol/L，P<0.01）的水平显著降低；FXR、SHP mRNA及蛋白表达水平显著上升（P<0.05），SREBP-1C
mRNA及蛋白表达则显著降低（P<0.05）。结论普罗布考改善NASH大鼠肝功及肝脏脂肪变性的作用与上调胆汁酸受体FXR
的表达水平有关。

Abstract: Objective To determine the effects of probucol on serum parameters and liver histopathology in rats with
non-alcoholic steatohepatitis (NASH) and explore the mechanisms. Methods Forty male Sprague-Dawley rats were randomly
assigned into 4 equal groups, namely the normal control group (NC group) with a standard feeding, high-fat diet group (HD
group) fed with a high-fat diet, probucol (500 mg/kg daily) control group (NP group) fed with standard diet, and probucol
group fed with a high-fat diet (HP group). After 15 weeks of feeding, the rats were euthanized for histopathological inspection
of the liver with HE staining and detection of farnesoid X receptor (FXR), SHP and SREBP-1C expressions using
semi-quantitative RT-PCR and Western blotting. Results After the 15-week feeding, the rats in HP group had significantly
lower levels of serum ALT, AST, cholesterol, bile acid, and free fatty acid than those in HD group (P<0.01 or 0.05). Compared
with the normal control group, high-fat diet feeding resulted in significantly decreased mRNA and protein levels of FXR and
SHP (P<0.05) and significantly increased SREBP-1C level (P<0.05). These high-fat diet-induced gene expression changes were
reversed by probucol intervention (P<0.05). Conclusion Probucol treatment has beneficial effects on serum parameters, hepatic
steatosis, and lobular inflammation in high-fat diet-induced NASH possibly by up-regulating FXR expression.