非酒精性脂肪性肝病模型大鼠饮食或二甲双胍干预后肝视黄醇结合蛋白4表达

Effects of dietary intervention versus metformin treatment on retinol binding protein4 expressions in rats with non-alcoholic fatty liver disease

背景:目前关于血清视黄醇结合蛋白4在非酒精性脂肪性肝病中的表达水平仍存在争议。目的:研究饮食或二甲双胍干预对非酒精性脂肪性肝病大鼠肝脏视黄醇结合蛋白4表达的影响。方法:将50只SD大鼠随机分为6组,8周对照组,正常饮食8周后处死;8周高脂组,高脂饮食8周制作非酒精性脂肪性肝病模型,随后处死;16周对照组,正常饮食16周后处死;16周高脂组,高脂饮食16周后处死;饮食干预组,8周高脂饮食后再正常饮食8周,随后处死;二甲双胍治疗组,8周高脂饮食后,继续8周高脂饮食,同时给予二甲双胍灌胃治疗,随后处死。采用ELISA法检测血清视黄醇结合蛋白4水平及生化指标,免疫组织化学法、Western blotting法、RT-PCR法检测肝脏组织视黄醇结合蛋白4表达。结果与结论:高脂饮食成功建立非酒精性脂肪性肝病大鼠模型,随造模时间延长,大鼠肝脏由单纯性脂肪肝逐渐进展成为脂肪性肝炎。饮食干预可改善高脂饮食引发的肝组织视黄醇结合蛋白4表达下降、肝功能异常、脂代谢紊乱和胰岛素抵抗,二甲双胍治疗仅改善了高脂饮食引发的肝脂肪变。结果表明肝组织视黄醇结合蛋白4表达的改变可能在非酒精性脂肪性肝病发病中起一定作用,饮食干预应作为防治非酒精性脂肪性肝病的基本措施,二甲双胍可以改善非酒精性脂肪性肝病的肝脂肪变。

BACKGROUND：Conflicting data have been reported regarding the expression of retinol-binding protein 4 in non-alcoholic fatty liver disease. OBJECTIVE：To evaluate the impact of dietary interventionversus metformin treatment on expression of retinol-binding protein 4 in rats with non-alcoholic fatty liver disease. METHODS： Fifty male Sprague-Dawley rats were randomized to six groups, including two normal control groups （rats were kiled after 8 and 16 weeks of normal diet）, two HFD groups （rats were kiled after 8 and 16 weeks of high-fat diet）, one dietary intervention group （rats were kiled after 8 weeks of high-fat diet and 8 weeks of normal diet） and one metformin treatment group （rats were kiled after 8 weeks of high-fat diet and 8 weeks of high-fat diet＆amp;nbsp;and metformin treatment）. The levels of retinol-binding protein 4 in serum and biochemical indexes were detected through enzyme-linked immunosorbent assay. The expression of retinol-binding protein 4 mRNA in liver tissues was measuredvia western blot analysis, immunohistochemistry and RT-PCR. RESULTS AND CONCLUSION：Non-alcoholic fatty liver disease models were successfuly established by high-fat diet. Liver tissues of high-fat diet fed rats showed progressing non-alcoholic fatty liver disease histology, from non-alcoholic fatty liver to non-alcoholic steatohepatitis. Dietary intervention increased retinol-binding protein 4 expression in liver tissue as wel as improving liver enzyme, dyslipidemia and insulin resistance, and aleviated impaired liver histology. Metformin treatment only aleviated hepatic steatosis caused by high-fat diet. The results indicated that retinol-binding protein 4 expression might play a role in the pathogenesis of non-alcoholic fatty liver disease. Metformin treatment can aleviate non-alcoholic fatty liver disease histology,dietary intervention should be the fundamental treatment.