六味地黄汤活性成分组方LW-AFC对高热量饲料诱导小鼠代谢综合征的改善作用  

Improvement effect of LW-AFC,an active component of prescription from Liuwei Dihuang decoction,on metabolic syndrome induced by high energy diet in mice

作　　者：郭妍[1] 迟晓丽 马渊[1] 肖智勇[1] 周文霞[1] 张永祥[1] 

机构地区：[1]军事医学科学院毒物药物研究所中药和神经免疫药理学研究室,北京100850

出　　处：《中国药理学与毒理学杂志》2013年第3期367-373,共7页Chinese Journal of Pharmacology and Toxicology

基　　金：国家科技重大专项(2009ZX09301-002);国家科技重大专项(2011ZX09102-101-07);国家自然科学基金(90709012);国家自然科学基金(30701073);全军医药卫生科研基金项目(2006203005)~~

摘　　要：目的研究中药新药LW-AFC对代谢综合征(MS)的作用及其作用机制。方法高热量饲料喂养昆明小鼠6周,同时每天ig给予二甲双胍(阳性对照药)0.2g·kg-1和LW-AFC 0.2,0.8和3.2g·kg-1。实验结束时测量小鼠体质量和摄食量,检测空腹血清总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、C肽、血糖(FBG)和胰岛素(FINS)含量,并计算稳态模型胰岛素抵抗评价指数(HOMA-IR);测定小鼠内脏脂肪质量(VFM)、计算内脏脂肪系数(VFC),并检测血清瘦素、抵抗素、肿瘤坏死因子α(TNF-α)、白细胞介素6(IL-6)和下丘脑神经肽Y(NPY)含量。TC和FBG含量用酶比色法检测,LDL-C和HDL-C含量用清除法检测,FINS和NPY含量用放射免疫分析法检测,C肽含量用均相酶联免疫法检测,瘦素、抵抗素、TNF-α和IL-6含量用液相芯片(luminex)法检测,并采用伊红染色法观察肝脏病理改变。结果与正常对照组比较,模型组小鼠腹型肥胖相关指标VFM和VFC、脂代谢相关指标TC和LDL-C和糖代谢相关指标FBG增高(P<0.01),肝细胞呈弥漫性小泡性脂变,日均摄食量增高(P<0.01),促食欲肽NPY、抑食欲激素瘦素和抵抗素增高(P<0.05)。与模型组比较,LW-AFC 0.2,0.8和3.2 g·kg-1可降低TC(P<0.05)和LDL-C(P<0.01)、升高HDL-C(P<0.05,P<0.01)等脂代谢相关指标水平,降低FBG,HOMA-IR和C肽(P<0.05,P<0.01)等糖代谢相关指标的水平,并可减轻肝脏小泡性脂变等病理损害,提示LW-AFC对模型小鼠糖脂代谢紊乱及肝脏病理损伤具有改善作用。LW-AFC 0.2,0.8和3.2g·kg-1可降低小鼠的日均摄食量和促食欲肽NPY水平(P<0.05),但可显著增高抑食欲激素瘦素的水平(P<0.01),提示LW-AFC对模型小鼠的食欲具有抑制作用。不同剂量的LW-AFC还可降低血清脂肪因子抵抗素和炎症细胞因子TNF-α和IL-6的水平(P<0.05,P<0.01);变量聚类分析结果表明,炎症因子IL-6与脂代谢关系密切,抑食欲激素瘦素与糖代谢关系密切,而�OBJECTIVE To evaluate the effect and mechanism of LW-AFC,an active component from Liuwei Dihuang decoction,against metabolic syndrome（MS） in a high-energy-diet induced model mice with similar characters of human MS.METHODS The models of high-caloric-diet-induced Kunming mice were ig given with metformin 0.2 g·kg-1 or LW-AFC 0.2,0.8 and 3.2 g·kg-1 consecutively for 6 weeks.At the end of the expreiment,the food intake and body mass of mice were dynamically weighted,and the fast blood total cholesterol（TC）,low density lipoprotein-cholesterol（LDL-C）,high density lipoprotein-cholesterol（HDL-C）,connecting peptide,glucose（FBG）,and fasting blood insulins（FINS） were measured.Homeostasis model assessment of insulin resistance（HOMA-IR） was calculated after that.The mice were sacrificed,and the coel-fat and orchio-fat were collected and weighted as visceral fat mass（VFM）,and the visceral fat coefficient（VFC） was calculated.The levels of serum leptin,resistin,tumor necrosis factor-α（TNF-α） and interleukin-6（IL-6）（Luminex method）,TC and FBG（oxidase method）,LDL-C and HDL-C（clearance method）,FINS and NPY（radioimmunoassay） were also detected.Histological micrographs of liver were stained by hematoxylin-eosin.RESULTSCompared with normal control group,TC,LDL-C,FBG,HOMA-IR and connecting peptide significantly decreased（P〈0.01） in diet induced mouse MS model.LW-AFC improved hepatic steatosis,decreased food intake（P〈0.05）,NPY（P〈0.05）,resistin（P〈0.05）,TNF-α（P〈0.05） and IL-6（P〈0.05,P〈0.01）,and increased leptin levels（P〈0.01）,though it had no effect on abdominal obesity and serum insulin levels.The variable cluster analysis showed that IL-6 level was close to lipid metabolism,the level of leptin was close to glucose metabolism,and resistin level was close to appetite and inflammation.CONCLUSION LW-AFC might improve MS by reducing hyperglycemia,improving dyslipidemia,increasing insulin sensitivity and reducing the pathologic damage

关 键 词：代谢综合征 高热量饲料 炎症 抵抗素 食欲 六味地黄汤 LW-AFC 

分 类 号：R285.5[医药卫生—中药学]