贞清方对2型糖尿病并发非酒精性脂肪肝大鼠LXRα表达的影响  

Regulation of Zhenqing Recipe on expression of hepatic LXRα in type 2 diabetic rats complicated with non-alcoholic fatty liver disease

作　　者：罗琼[1] 文秀英[1] 鲁敏[1] 许明旺[2] 熊亮[3] 

机构地区：[1]华中科技大学同济医学院附属梨园医院内分泌科,湖北省武汉市430077 [2]华中科技大学同济医学院附属梨园医院老年病研究所,湖北省武汉市430077 [3]华中科技大学同济医学院附属梨园医院检验科,湖北省武汉市430077

出　　处：《世界华人消化杂志》2009年第14期1394-1401,共8页World Chinese Journal of Digestology

基　　金：国家自然科学基金资助项目; No. 30672730~~

摘　　要：目的:探讨贞清方对2型糖尿病非酒精性脂肪肝的治疗作用及可能机制.方法:高脂高糖饮食结合小剂量链脲佐菌素(STZ)腹腔注射建立2型糖尿病并发非酒精性脂肪肝大鼠模型.将成模大鼠随机分为模型组、贞清方治疗组和女贞子治疗组(n=8),并设立正常对照组(n=10),灌胃治疗8wk.比较喂养4、8和16wk时各组大鼠空腹血糖(FBG)、血清甘油三酯(TG)、总胆固醇(TC)、胰岛素(FINs)和胰岛素敏感指数(ISI)的变化.并于喂养16wk时观察各组大鼠肝脏指数、TG含量和血清丙氨酸转氨酶(ALT)的水平以及病理变化.用PCR法观察大鼠肝X受体(LXRα)及其下游固醇调节元件结合蛋白-1c(SREBP-1c) mRNA的表达,免疫组织化学法观察肝脏LXRα蛋白的表达.结果:灌胃干预8wk后,与正常组相比,模型组大鼠FBG、血清TG、肝脏指数及肝脏TG含量明显升高(均P<0.01),胰岛素敏感性明显降低(P<0.01),肝脏脂肪变明显加重,肝脏LXRα mRNA、SREBP-1c mRNA和LXRα蛋白的表达明显增多(均P<0.01).与模型组相比,贞清方治疗组大鼠FBG水平、血清TG水平、肝脏指数及肝脏TG含量明显降低(10.94±3.33mmol/L vs 16.67±4.33mmol/L;0.79±0.27mmol/L vs 1.33±0.33mmol/L;5.72±0.81 vs 7.61±1.24;0.041±0.0110mmol/gvs0.059±0.0160mmol/g,均P<0.01),肝脏脂肪变明显改善,肝脏LXRαmRNA、SREBP-1c mRNA和LXRα蛋白的表达明显减少(0.75±0.11vs1.23±0.17,0.68±0.16 vs 1.07±0.14,0.220±0.071 vs 0.334±0.037,均P<0.01).结论:贞清方对2型糖尿病性非酒精性脂肪肝具有一定的治疗作用,且其治疗作用可能与贞清方能下调非酒精性脂肪肝组织LXRα的表达有关.AIM： To investigate prevention and functional mechanism of Zhengqing Recipe （ZQR） in the models of type 2 diabetic rats complicated with non-alcoholic fatty liver disease METHODS： The model of type 2 diabetic rats complicated with non-alcoholic fatty liver was established by feeding high-glucose and highfat diet, and injection of low dose streptozotocin. The model rats were randomly divided into four groups： model group, ZQR group and fructus ligustri lucidi group （n = 8）, and normal control group （n = 10）. Intragastric administration lasted for 8 wk. On 4 wk, 8 wk and 16 wk, the levels of fasting blood glucose （FBG）, fasting serum in- sulin （FINs）, serum triglyceride （TG） and serum total cholesterol （TC） in each group were tested and the level of insulin sensitivity index （ISI） was calculated. On 16 wk, serum alanine ami- notransferase （ALT）, index of liver and liver TG content in each group were examined as well. Meanwhile, pathological changes of liver, the expression of liver X receptor α （LXRα mRNA, sterol regulatory element-binding protein-1c （SREBP-1c） mRNA and LXRα protein of liver tissues in each group were detected. RESULTS： After treatment for 8 wk, the levels of FBG, serum TG and TC, index of liver and liver TG content were significantly higher （all P 〈 0.01）, ISI was significantly lower （P 〈 0.01）, liver cirrhosis was significantly exacerbated, and the expressions of LXRα mRNA,SREBP-1c mRNA and LXRα protein were significantly increased （all P 〈 0.01） in model group compared with control group. Compared with model rats, the levels of FBG, serum TG, index of liver and liver TG content were significantly lower （10.94 ± 3.33 mmol/L vs 16.67 ± 4.33 mmol/L; 0.79 ± 0.27 mmol/L vs 1.33 ± 0.33 mmol/L; 5.72±0.81 vs 7.61 ± 1.24; 0.041 ± 0.0110 mmol/g vs 0.059± 0.0160 retool/g, all P 〈 0.01）. Liver cirrhosis was significantly improved, and the expressions of LXRαmRNA,SREBP-1c mRNA and LXRα protein were significantly decrease

关 键 词：2型糖尿病 非酒精性脂肪肝 肝X受体α固醇调节元件结合蛋白-1c 贞清方 大鼠 

分 类 号：R285.5[医药卫生—中药学]