槲皮素对大鼠非酒精性脂肪性肝病的疗效及其机制  

fatty liver disease Therapeutic efficacy and mechanisms of quercetin in a rat model of nonalcoholic

作　　者：周冬生[1] 梁志清[1] 秦青[1] 张茂华[1] 李胜联[1] 

机构地区：[1]广西桂林医学院附属医院感染性疾病科,桂林541001

出　　处：《中华肝脏病杂志》2013年第2期134-137,共4页Chinese Journal of Hepatology

基　　金：广西科技厅自然科学基金（桂科自0991263）;桂林市科学研究与技术开发计划项目（20090539）;广西卫生厅自筹经费科研课题项目（Z2009036）

摘　　要：目的观察槲皮素对非酒精性脂肪性肝病（NAFLD）的治疗效果，并初步探讨其作用机制。方法100只SD大鼠随机分为正常对照组（正常组）、模型对照组（模型组）、槲皮素低剂量治疗组（低剂量组）、槲皮素高剂量治疗组（高剂量组）；采用高脂饲料构建NAFLD大鼠动物模型，成功建模后用槲皮素低、高剂量进行干预治疗8周。检测并比较各组大鼠肝指数、空腹血糖（EBS）、甘油三酯、白细胞介素（IL）18、IL一10、丙二醛水平，观察各组大鼠肝组织病理学的改变情况。正常组与模型组间均数比较采用两组独立样本的f检验；槲皮素治疗前后各组间进行单因素方差分析，用LSD-t检验进行两两比较；相关分析用Pearson法。结果模型组与正常组相比，肝指数、FBS、甘油三酯、IL-18、丙二醛水平显著增高，IL一10水平降低（t值分别为2．46，5．12，5．24，4．82，3．45，-2．23，P值均〈0．05）；电子显微镜下肝脏出现明显炎症和脂肪变性，相关分析提示IL-18水平与炎症程度呈正相关（r=0．714，JP〈0．05），IL-10水平与炎症和脂肪变性程度呈负相关（，值分别为一0．64，一0．463，P值均〈0．05）。经槲皮素干预后，肝指数、FBS、IL-18水平显著下降∽值分别为10．29，10．28，60．59，P值均〈0．05），IL-10上升（F=52．584，P〈0．01）；高剂量组改变更明显。结论在NAFLD大鼠血清中IL_18表达增高，IL-10下降，且与肝脏炎症和脂肪变性有一定相关性，槲皮素可能通过调节炎症细胞因子的平衡而延缓NAFLD的进展。Objective To determine the efficacy of the plant-derived bioflavonoid, quereetin, for treating nonalcoholic fatty liver disease （NAFLD） by using a rat model, and to investigate the molecular mechanism underlying its therapeutic effects. Methods One-hundred Sprague-Dawley rats were randomly assigned into the normal control group （normal group）, untreated NAFLD model control group （model group）, 75 mg/kg/day quercetin treatment group （low-dose group）, and 300 mg/kg/day quercetin treatment group （high-dose group）. The NAFLD rat model was established by providing four weeks of a high-fat diet; the normal group received normal rat chow diet. The quercefn treatments were administered for eight weeks after model establishment and control groups received simultaneous gavages of isotonic saline, with continuation of the respective diets. At the end of the eight weeks （experimental week 12）, the rats were sacrificed for liver and serum collection. Intergroup differences in liver index, fasting blood glucose （FBG）, triglycerides fiG）, interleukin （IL）-18, IL-10, malondialdehyde （MDA）, and histopathological features were assessed by independent samples t-test （normal vs. model）, one-way ANOVA （model vs. treatments）, and least significant difference t-test （pairwise comparisons）; correlations were assessed bv Pearson＇s correlation coefficient. Results Compared with the normal ~roun. the model m＇oun showedsignificantly higher liver index （t = -2.327）, FBG （t ^- -3.482）, TG （t = -0.302）, and serum IL-18 （t = -2.704） （all P 〈 0.05）, but significantly lower 1L-10 （t = 2.622, P 〈 0.05）; the MDA level was also higher in the model group, but the difference was not significant （t= -I.083,P〉 0.05）. Livers from the model group showed obvious histological features of inflammation （lymphocyte and neutrophil infiltration） and steatosis （cytoplasmic lipid droplets）. Inflammation was positively correlated with IL-18 （P 〈 0.05）, but negative

关 键 词：脂肪肝 白细胞介素10 白细胞介素18 槲皮素 

分 类 号：R285.5[医药卫生—中药学]