傣百解醇提物调控趋化素表达发挥对非酒精性脂肪肝大鼠治疗作用

目的 研究傣百解醇提物对非酒精性脂肪肝大鼠的治疗作用，并探讨其调控趋化素（Chemerin）及其受体（CMKLRI）表达的作用机制。方法 高脂饲料喂养8周建立非酒精性脂肪肝（NAFLD）大鼠模型，验证造模成功后改普通饲料喂养，并随机分为模型组、非诺贝特胶囊组（阳性药，0.2 g/kg）和傣百解醇提物低、高（2.6、4.5 g/kg）剂量组，每组10只，给药组每天ig给药1次，连续4周；对照组大鼠一直饲予普通饲料，对照、模型组给予等体积纯水。最后1次给药后大鼠禁食不禁水12 h，腹主动脉取血收集血清，于全自动生化分析仪上测定血清总胆固醇（TC）、三酰甘油（TG）、游离脂肪酸（FFA）、低密度脂蛋白胆固醇（LDL-C）、高密度脂蛋白胆固醇（HDL-C）、空腹血糖（FBG）水平；ELISA法检测血清空腹胰岛素（FINS）的浓度；计算胰岛素敏感指数（ISI）和胰岛素抵抗指数（HOMA-IR）。取肝组织进行HE染色，光学显微镜下观察肝组织病理学改变。实时荧光定量PCR（qRT-PCR）法检测肝组织Chemerin及CMKLRI mRNA表达水平。结果 与模型组比较，傣百解醇提物高、低剂量组血清TC水平均显著降低（P<0.05），低剂量组HDL-C含量显著升高（P<0.05）；各剂量组HOMA-IR水平均降低，其中高剂量组差异显著（P<0.05）；各剂量组ISI均有所升高，但作用均无统计学差异；高、低剂量组肝脏脂质沉积等病理学改变有所改善；各剂量组Chemerin及CMKLRI mRNA表达均有所下调，其中高剂量组下调Chemerin mRNA表达作用显著（P<0.05）。结论 傣百解醇提物对大鼠NAFLD具有降低LDL-C、升高HDL-C含量、降低HOMA-IR水平和保肝作用，其作用机制可能与下调chemerin mRNA表达有关。

Effect of Dai Baijie Ethanol Extract on Chemerin and its receptors in rats with nonalcoholic fatty liver

Objective To study the therapeutic effect of ethanol extract of Dai Baijie (Ya Jie Xian Da) on non-alcoholic fatty liver rats, and to explore the mechanism of its regulation of Chemokine and its receptor (CMKLRI) expression. Method Non-alcoholic fatty liver (NAFLD) rat model was established by feeding high-fat diet for eight weeks. The rats were fed with normal diet after successful modeling. The rats were randomly divided into model group, fenofibrate capsule group (positive drug, 0.2 g/kg) and Dai Baijie alcohol extract low and high dose group (2.6 and 4.5 g/kg). Each group had 10 rats, and the treatment group was ig given once a day for four weeks, rats in control group were fed normal diet, and the control group and model group were given equal volume pure water. After fasting for 12 hours, blood samples were collected from abdominal aorta. Total cholesterol (TC), triglyceride (TG), free fatty acid (FFA), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and fasting blood glucose (FBG) were measured by automatic biochemical analyzer. Levels of insulin, fasting insulin (FINS) and insulin sensitivity index (ISI) and insulin resistance index (HOMA-IR) were measured by ELISA. Liver tissues were stained with HE, and pathological changes of liver tissues were observed under light microscope. Real time fluorescence quantitative PCR (qRTPCR) was used to detect the expression level of Chemerin and CMKLRI mRNA in liver tissue. Results Comparison with the model group, after the intervention of Dai BaiJie (Ya Jie xian da) ethanol extract, The content of TC in serum in each dose group was decreased significantly (P<0.05), and the content of HDL-C in the low dose group was increased significantly (P<0.05). The levels of HOMA-IR in each dose group were decreased, and the difference was found in the high dose group; the ISI in each dose group was increased, but the effect was not statistically significant; the pathological changes such as liver lipid deposition were improved in the high and low dose groups; the expressions of Chemerin and CMKLRI mRNA in each dose group were downregulated, and the Chemerin mRNA expression down-regulated in the high dose group was remarkable. Conclusion Dai Baijie alcohol extract can reduce LDL-C, increase HDL-C content, decrease HOMA-IR level and protect liver in rats with NAFLD. The mechanism may be related to down-regulation of Chemerin mRNA expression.