CAJ | 학술논문

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±17.7μmol/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。
목적：탐토강지약물보라포고대비주정성지방성간염대서간장병리、혈청학지표적개선작용、대간장담즙산수체FXR급하유기인、단백SHP、SREBP-1C표체적영향。방법웅성SD대서40지，수궤평균분4조：（1）정상대조조，여보통사료；（2）고지조，여고지사료；（3）보라포고대조조，여보통사료급보라포고관위（500 mg/kg· d-1）；（4）보라포고간예조，여고지사료급보라포고관위（500 mg/kg· d-1）。15주후처사，검측각조대서혈청전안매、혈지、담즙산，동시취간조직，절편행HE염색급병리평분；RT-PCR급Western Blot적방법검측간조직FXR、SHP급SREBP-1C기인급단백적표체수평。결과여고지조비교，보라포고간예조간장지방변성급염증침윤정도명현감경，혈청ALT（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）급담고순（2.7±0.2 vs 2.4±0.3 mmol/L，P<0.01）、유리지방산（0.734±.0.11 vs 0.557±0.19 mmol/L，P<0.05），담즙산（48.3±11.6 vs 24.9±17.7μmol/L，P<0.01）적수평현저강저；FXR、SHP mRNA급단백표체수평현저상승（P<0.05），SREBP-1C mRNA급단백표체칙현저강저（P<0.05）。결론보라포고개선NASH대서간공급간장지방변성적작용여상조담즙산수체FXR적표체수평유관。
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.