胰岛素抵抗大鼠的肝脏中丝氨酸/酪氨酸磷酸化异常与血清TNF-α相关

目的探讨胰岛素抵抗大鼠胰岛素受体底物-1丝氨酸/酪氨酸磷酸化与肿瘤坏死因子α（TNF-α）的关系。方法雄性Wistar大鼠30只（体质量80-120 g）,随机分为普通饮食组（NC）及高脂饮食组（FH）2组,每组15只。喂养10周,以高胰岛素-正常血糖钳夹技术评估胰岛素抵抗大鼠模型。应用ELISA法检测大鼠血清TNF-α含量,Western Blot法检测肝脏组织中胰岛素受体底物-1丝氨酸磷酸化（IRS-1Ser636）及酪氨酸磷酸化（IRS-1Tyr465）表达。结果FH组葡萄糖输注率（GIR）60-120水平明显低于NC组[（1.56±0.43 vs.5.15±0.66）mg/（kg.min）,P〈0.01];FH组大鼠TNF-αI、RS-1Ser636均高于NC组[（15.43±2.16 vs.5.4±2.16）pg/mL,P〈0.01;（109.45±13.75 vs.94.23±15.05）,P〈0.05],IRS-1Tyr456水平低于NC组[（111.08±14.28 vs.125.77±14.51）,P〈0.05]。TNF-α水平与IRS-1Ser636呈正相关（r=0.503,P=0.024）,与IRS-1Tyr465呈负相关（r=-0.521,P=0.019）。结论胰岛素抵抗大鼠TNF-α水平与IRS-1Tyr465负相关,与IRS-1Ser636正相关,提示TNF-α引起胰岛素抵抗机制可能与IRS-1磷酸化异常有关。     

运动干预对胰岛素抵抗大鼠骨骼肌IL-1β表达的影响

目的观察运动干预对高脂饲料诱导胰岛素抵抗（IR）大鼠白细胞介素1β（IL-1β）表达的影响,探讨运动减轻IR的可能机制。方法健康Wistar雄性大鼠分为基础饲料喂养组（normal chow group,NC）,高脂膳食喂养组（high-fat diet group,HF）。高脂膳食喂养Wistar雄性大鼠10周,构建IR动物模型。10周后,HF组再随机分为高脂喂养运动组和非运动组,游泳运动干预4周。游泳运动干预前后以正常血糖-高血浆胰岛素钳夹实验技术[hyperinsulinemic-euglycemic clamp（HEC）technique]评估IR大鼠胰岛素敏感性,ELISA法测定大鼠血清IL-1β水平,RT-PCR法测定大鼠骨骼肌IL-1βmRNA表达。结果HF组大鼠葡萄糖输注率（glucose infusion rate,GIR）显著低于NC组（P〈0.05）,HF组血清IL-1β水平及骨骼肌组织IL-1βmRNA表达明显高于NC组（P〈0.05,P〈0.01）;运动组大鼠血清IL-1β水平及骨骼肌组织IL-1βmRNA表达明显低于非运动组（P〈0.05）,与NC组差异无显著性（P〉0.05）。结论运动改善IR大鼠胰岛素敏感性,可能与降低IR大鼠IL-1β的表达有关。     

不同强度电针对肥胖大鼠脂肪组织炎症相关因子的影响

探讨不同强度电针对肥胖大鼠脂肪组织核因子-κBp65(NF-κBp65)、单核细胞趋化蛋白-1(MCP-1)和肿瘤坏死因子-α(TNF-α)的作用差异.将SD大鼠随机分为普通饮食组、高脂饮食组、5 V电针组、2.5 V电针组,除普通饮食组外其余各组大鼠均饲以高脂饲料.取"足三里"、"三阴交"穴,不同强度电针治疗14 d后,用蛋白质印迹技术(Western blot)检测肥胖大鼠附睾脂肪组织NF-κBp65的表达,酶联免疫吸附法(ELISA)检测肥胖大鼠附睾脂肪组织MCP-1、TNF-α的含量.研究发现两电针组肥胖大鼠体重、Lee’s指数、脂肪组织中NF-κBp65表达、MCP-1和TNF-α含量较高脂饮食组显著降低(P<0.01),5 V电针组较2.5 V电针组下降效果更为明显(P<0.01,P<0.05).结果表明电针可改善肥胖脂肪组织炎症反应状态,减轻肥胖大鼠体重,且5 V电针组效果优于2.5 V电针组.     

表没食子儿茶素没食子酸酯对高脂饮食大鼠脂肪组织TNF-α表达的影响及意义

目的 探讨表没食子儿茶素没食子酸酯（EGCG）对高脂饮食大鼠脂肪组织中肿瘤坏死因子-α（TNF-α）表达的影响及其与胰岛素敏感性的相关性.方法 将30只SPF级雄性SD大鼠随机分为正常饮食组（ND组,n=10）和高脂饮食组（HFD组,n=20）.喂养16w,当两组大鼠体质量出现显著差异后（P〈0.05）,将HFD组按随机区组原则分为单纯高脂组（HFD组,n=10）和EGCG干预组（HFD＋0.32%EGCG,EGCG组,n=10）.干预16w.留取血清及附睾周脂肪组织.检测每组大鼠空腹血糖（FBG）、胰岛素水平（FINS）及游离脂肪酸（FFAs）,并计算胰岛素抵抗指数（HOMA-IR）;应用Real-time PCR及Western blot方法检测附睾周脂肪组织中TNF-α表达水平.结果 （1）与HFD组相比,EGCG组FINS水平显著下降[分别为（13.83±0.79）mIU/l vs.（31.71±3.61）mIU/l,P〈0.05];HOMA-IR值下降[分别为（3.36±0.31） vs.（7.59±0.99）,P〈0.05];FFAs值亦明显下降[分别为（0.38±0.08）mmol/l vs.（0.81±0.11）mmol/l,P〈0.05];三组大鼠FBG水平无明显统计学差异（P〉0.05）.（2）与ND组相比,HFD组脂肪组织中TNF-αmRNA水平显著升高[分别为（0.0033±0.00070）vs.（0.0010±0.00008）,P〈0.01];而EGCG组较HFD组则明显下降[分别为（0.0018±0.00037）vs.（0.0033±0.00070）,P〈0.05];同时,EGCG组TNF-α蛋白表达量低于HFD组[分别为（0.42±0.09）vs.（0.67±0.09）,P〈0.05];（3）EGCG组与ND组无明显差异（P〉0.05）.结论 EGCG改善高脂饮食大鼠胰岛素敏感性可能与减轻脂肪组织TNF-α介导的炎症状态相关.     

HE4、NF-κBp65和MMP-9在卵巢上皮性肿瘤中的表达及其临床意义

目的探讨HE4、NF-κBp65以及MMP-9的表达与上皮性卵巢肿瘤临床病理生物学行为的关系以及对患者预后的影响。方法应用免疫组化对80例卵巢上皮性癌、10例交界性上皮性肿瘤及10例良性上皮性肿瘤组织进行HE4、NF-κB p65及MMP-9蛋白的检测。结果 HE4、NF-κBp65及MMP-9蛋白的阳性表达率在卵巢癌组均高于交界性及良性肿瘤组（P〈0.05）。三个指标的表达与EOC的组织学分级、腹腔脏器及淋巴结转移以及PTNM临床分期有关（P〈0.05）;在EOC中,NF-κBp65分别与HE4、MMP-9的表达呈正相关（r1=0.673,P〈0.05;r2=0.775,P〈0.05）。多因素分析,PTNM分期、MMP-9的表达是影响卵巢癌术后患者预后的独立因素（P〈0.05）;HE4阳性组与阴性组5年生存率分别为12.7%和84.0%,MMP-9阳性组与阴性组5年生存率分别为8.7%和70.6%,差异均有统计学意义（P〈0.05）。结论 NF-κBp65可能通过上调HE4、MMP-9的表达促进EOC的浸润和转移,联合检测HE4、NF-κBp65以及MMP-9的表达可能作为预测和评价患者预后的生物学指标。     

慢性重度乙型肝炎患者肝组织中NF-κBp65和Caspase-3的表达及其意义

目的：探讨慢性重度乙型肝炎患者肝组织中NF-κBp65和Caspase-3的表达及其意义。方法：选择慢性重度乙型肝炎肝组织标本68例（慢重肝组）,正常肝组织标本20例（对照组）。采用免疫组化方法检测肝组织中NF-κBp65和Caspase-3的表达。结果：慢重肝组患者肝组织中NF-κBp65和Caspase．3阳性表达程度均明显强于对照组（P〈0．05）;慢重肝患者死亡组肝组织中NF-κBp65和Caspase．3阳性表达程度均明显强于存活组（P〈O．05）。Spearman相关分析发现,慢重肝组患者肝组织中NF-κBp65和Caspase-3表达之间有明显的正相关性（r=0．449,P〈0．05）。结论：NF-κBp65和Caspase-3可能参与了慢性重度乙型肝炎的肝细胞凋亡过程,且具有一定相关性,并对判断患者预后有重要临床价值。     

中介素1-53对肺缺血再灌注损伤大鼠NF-κB和CINC-1的影响

目的探讨中介素1-53对大鼠肺缺血再灌注损伤后核因子-κB（NF-κBp65）和细胞因子诱导的中性粒细胞趋化物（CINC-1）蛋白表达的影响。方法将健康Wistar大鼠54只随机分为手术对照组（C组）、缺血再灌注组（IR组）、中介素干预组（D组）。每组分别在缺血45min,再灌注60min、120min 3个时点处死6只大鼠,观察肺组织病理形态变化,测定肺组织湿干质量比值（W/D）、髓过氧化物酶（MPO）活性,肺组织匀浆CINC-1蛋白含量及NF-κBp65蛋白的表达。结果 IR组的W/D值、MPO活性、NF-κBp65和CINC-1的蛋白表达均高于C组,中介素1-53干预后各值较IR组有所下降;D组肺组织病理学变化较IR组明显减轻。结论中介素1-53的应用可以减轻肺缺血再灌注损伤,作用机制可能与其抑制NF-κB的活化,降低肺组织CINC的表达,从而减少肺内PMN的浸润密切相关。     

替米沙坦抑制SOCS-3/SREBP-1c通路改善非酒精性脂肪性肝炎模型大鼠的胰岛素抵抗

目的探讨替米沙坦对高脂饮食诱导的非酒精性脂肪性肝炎大鼠肝组织SOCS-3通路的抑制作用及对胰岛素抵抗的干预作用。方法 70只雄性SD大鼠随机分为A(20只,正常对照)、B(30只,模型对照)和C组(20只,实验干预)。A组大鼠喂以普通饲料,B和C组喂以高脂饲料;12周末随机处理B组10只,行正葡萄糖高胰岛素钳夹试验,证实IR-NASH造模成功(100%)后,B、C两组继续高脂喂养,并予C组大鼠替米沙坦每日5 mg/kg灌胃,16周末全部大鼠测血清IL-6、TG、TC、ALT、AST、空腹血糖(FBG)和血清胰岛素(FBI),并计算胰岛素抵抗指数;行正葡萄糖高胰岛素钳夹试验,肝组织HE肝脏病理学检查,半定量RT-PCR法检测肝组织SOCS-3和SREBP-1c mRNA表达水平。结果高脂饮食12周大鼠进展为NASH。16周末,B组大鼠肝湿重显著高于A组,C则明显低于B组;B组出现血脂异常和IR,血清IL-6、肝脏SOCS-3 mRNA和SREBP-1c mRNA表达水平明显上调(与A组比较P0.01),三者分别与稳态葡萄糖输注率(VGIR60-120)显著负相关(r=0.9248,P0.0001;r=0.9011,P0.0001;r=0.9739,P0.0001)。替米沙坦干预后,肝功能和血脂异常明显改善,NASH病理明显好转,SOCS-3 mRNA和SREBP-1c mRNA较B组显著下调(P0.01),同时VGIR60-120明显增高(r=0.9532,P0.0001;r=0.9687,P0.0001),表明IR明显改善;而此时IL-6仍高水平,与VGIR60-120、SOCS-3、SREBP-1c失去相关关系(r=0.0071,P=0.7238;r=0.0019,P=0.8560;r=0.0002,P=0.9586),而SOCS-3 mRNA和SREBP-1c mRNA仍显著相关(r=0.9439,P0.0001)。结论替米沙坦干预NASH大鼠可显著减改善肝功能和IR,其机制并非抑制炎症因子IL-6,而是下调肝脏SOCS-3、SREBP-1c的表达,从而改善糖脂代谢和NASH。     

Dll4蛋白在高脂饮食喂养大鼠脂肪组织炎症中的作用

目的 探讨Delta-like ligand 4（Dll4）蛋白在高脂饮食喂养大鼠脂肪组织中的表达及其与脂肪组织炎症的关系.方法 将20只SPF级雄性Sprague-Dawley大鼠随机分为正常饮食组（SD,n=10）和高脂饮食组（HFD,n=10）喂养16w后,应用免疫组化及Western blot方法检测脂肪组织中Dll4及炎症通路NF-κB磷酸化、IL-6的表达.结果 免疫组化结果显示,HFD组Dll4表达量显著升高（P〈0.001）;Western blot结果与免疫组化结果相一致,Dll4蛋白表达量是SD组的1.34倍（P〈0.01）;磷酸化核转录因子NF-κB表达水平升高,HFD组为SD组的2.03倍（P〈0.01）;HFD组炎症细胞因子IL-6水平明显升高,为SD组的3.02倍（P〈0.01）.结论 高脂饮食可增加脂肪组织中Dll4蛋白表达,促进了脂肪组织中炎症的发生.     

NF-κB介导非对称性二甲基精氨酸上调大鼠主动脉诱导型一氧化氮合酶的表达

目的探讨非对称性二甲基精氨酸(ADMA)上调大鼠主动脉诱导型一氧化氮合酶(iNOS)的表达是否是通过激活NF-κB实现的。方法 Wistar大鼠50只随机分为四组:①对照组(n=10):标准饲料喂养。②H组(n=12):高脂饲料喂养。③A+H组(n=14):予ADMA[0.2mg/kgd]灌胃,高脂饲料喂养。④P+A+H组(n=14):予吡咯烷二硫代氨基甲酸盐(pyrrolidine dithiocarbamate,PDTC)[40mg/kgd]腹腔注射、ADMA[0.2mg/kgd]灌胃、高脂饲料喂养。对照组、H组予等体积的生理盐水灌胃及腹腔注射、A+H组给予等体积的生理盐水腹腔注射。18周后麻醉大鼠、取主动脉。以实时荧光定量PCR和Westen blotting分别检测iNOS mRNA和蛋白表达,以电泳迁移率变动分析(EMSA)和增强化学发光法(ECL)检测NF-κB活性。结果①A+H组iNOS mRNA和蛋白表达量较对照组和H组增加(P<0.05),P+A+H组较A+H组iNOSmRNA和蛋白表达量降低(P<0.05)。②A+H组NF-κB活性较对照组和H组显著升高(P<0.05),P+A+H组NF-κB活性较A+H组明显降低(P<0.05)③相关分析:NF-κB活性与iNOS mRNA和蛋白表达量呈正相关(相关系数r分别为0.854、0.876,P<0.05)。结论 ADMA可能通过激活NF-κB途径上调iNOS表达,从而促进动脉粥样硬化的发生发展。     

Postweaning low-calcium diet promotes later-life obesity induced by a high-fat diet

The aim of this study was to investigate the effects of a postweaning low-calcium diet on later obesity and explore the underlying mechanisms. Ninety-six male rats were weaned at 3 weeks of age, fed standard (STD: 0.50% calcium, n=48) and low-calcium (LC: 0.15% calcium, n=48) diets for 3 weeks, and then fed the standard diet for a 3-week washout period successively. Finally, the STD rats were divided into STD control and high-fat diet (HFD) groups, and the LC ones into LC control and LC+HFD (LCHF) groups. The STD and LC rats were fed the standard diet, while the HFD control and LCFD ones were fed a high-fat diet for 6 weeks to induce obesity. During the three feeding periods, adenosine-monophosphate-activated protein kinase (AMPK) and its responsive proteins phospho-acetyl-coA carboxylase, carnitine palmitoyltransferase 1 and uncoupling protein 3 were persistently down-regulated in the LC group (decreased by 18%, 24%, 18% and 20%, respectively) versus the STD group, and these effects were significantly more pronounced in the LCHFD group (decreased by 21%, 30%, 23% and 25%, respectively) than the HFD group by a later high-fat stimuli, causing more fat and body weight in adulthood. However, lipolysis enzymes, serum leptin, insulin and lipids were not significantly affected until the body weight and fat content changed at 15 weeks of age. The results suggest that the low-calcium diet after weaning promotes rat adult-onset obesity induced by high-fat diet, which might be achieved by programming expressions of genes involved in AMPK pathway.     

Exercise reduces adipose tissue via cannabinoid receptor type 1 which is regulated by peroxisome proliferator-activated receptor-delta

Obesity is one major cardiovascular risk factor. We tested effects of endurance exercise on cannabinoid receptor type 1 (CB1) and peroxisome proliferator-activated receptor-delta (PPAR-delta)-dependent pathways in adipose tissue. Male Wistar rats were randomly assigned to standard laboratory chow or a high-fat diet without and with regular endurance exercise. Exercise in rats on high-fat diet significantly reduced visceral fat mass, blood pressure, and adipocyte size (each p<0.05). Adipocyte hypertrophy induced by high-fat diet was accompanied by increased CB1 expression in adipose tissue, whereas exercise significantly reduced CB1 expression (each p<0.05). CB1 receptor expression and adipocyte differentiation were directly regulated by PPAR-delta. Adipocyte hypertrophy induced by high-fat diet was accompanied by reduced PPAR-delta. Furthermore, selective silencing of PPAR-delta by RNA interference in 3T3-L1-preadipocyte cells significantly increased CB1 expression from 1.00+/-0.06 (n=3) to 1.91+/-0.06 (n=3; p<0.01) and increased adipocyte differentiation, whereas adenovirus-mediated overexpression of PPAR-delta significantly reduced CB1 expression to 0.39+/-0.03 (n=3; p<0.01) and reduced adipocyte differentiation. In the presence of the CB1 antagonist rimonabant adipocyte differentiation in stimulated 3T3 L1 preadipocyte cells was significantly reduced. The study indicates that high-fat diet-induced hypertrophy of adipocytes is associated with increased CB1 receptor expression which is directly regulated by PPAR-delta. Both CB1 and PPAR-delta are intimately involved in therapeutic interventions against a most important cardiovascular risk factor.     

Variation in Gene Expression of Inflammatory Cytokines in Leukocyte-Derived Cells of High-Fat-Diet-Induced Insulin-Resistant Rats

A high-fat diet is thought to enhance inflammation in various tissues by increasing insulin resistance. In this study, we determined the mRNA levels of inflammatory cytokines in leukocyte-derived cells in the blood of rats with high-fat-diet-induced insulin resistance. Feeding rats a high-fat diet for 77 d induced moderate insulin resistance, which was determined by increased plasma glucose and insulin concentrations, following an oral glucose tolerance test. The interleukin (IL)-1β mRNA level was higher in the insulin-resistant rats than in control rats at the fasting stage, whereas the tumor necrosis factor (TNF)-α mRNA level was greatly elevated at 180 min after glucose administration in the insulin-resistant rats. The results suggest that feeding rats a high-fat diet enhances the expression of fasting IL-1β and postprandial TNF-α genes in leukocyte-derived cells.     

Benfluorex improves muscle insulin responsiveness in middle-aged rats previously subjected to long-term high-fat feeding

It has been reported that benfluorex ameliorates the insulin resistance induced by high-fat feeding when its administration is initiated at the same time as the change in diet. Here we have examined whether benfluorex reverses insulin resistance when this is established in middle-aged rats chronically maintained on a high-fat diet. Untreated 12-month-old rats that had been subjected to a high-fat diet for the last 6 months showed markedly lower insulin-induced stimulation of 2-deoxyglucose uptake by strips of soleus muscle and a reduced expression of GLUT4 glucose carriers in skeletal muscle. However, animals subjected to the same protocol but treated with benfluorex during the last month of high-fat feeding showed marked improvement in insulin-stimulated glucose transport by soleus muscle. Benfluorex treatment caused a substantial increase in the content of GLUT4 protein in white muscle; however, GLUT4 levels in red muscle remained low. Our results indicate: (i) that benfluorex treatment in middle-aged rats reverses the insulin resistance induced by high-fat feeding in soleus muscle; (ii) benfluorex is active even when it is administered once the insulin-resistant state is already established; (iii) reversion of muscle insulin resistance by benfluorex can occur independently of modifications in GLUT4 protein expression.     

Variation in gene expression of inflammatory cytokines in leukocyte-derived cells of high-fat-diet-induced insulin-resistant rats

A high-fat diet is thought to enhance inflammation in various tissues by increasing insulin resistance. In this study, we determined the mRNA levels of inflammatory cytokines in leukocyte-derived cells in the blood of rats with high-fat-diet-induced insulin resistance. Feeding rats a high-fat diet for 77 d induced moderate insulin resistance, which was determined by increased plasma glucose and insulin concentrations, following an oral glucose tolerance test. The interleukin (IL)-1beta mRNA level was higher in the insulin-resistant rats than in control rats at the fasting stage, whereas the tumor necrosis factor (TNF)-alpha mRNA level was greatly elevated at 180 min after glucose administration in the insulin-resistant rats. The results suggest that feeding rats a high-fat diet enhances the expression of fasting IL-1beta and postprandial TNF-alpha genes in leukocyte-derived cells.     

下丘脑Orexin 对肥胖大鼠能量代谢的影响

目的:探讨下丘脑注射OXR-1选择性受体拮抗剂ACT-335827对肥胖大鼠代谢的效果。方法:通过高脂饮食建立肥胖大鼠模型,采用CODA 8通道高通量非侵入性血压系统(EMKA)测量血压;所有脂类都使用商品酶试剂盒和TOSHIBA-40FR全自动分析仪测量;空腹血糖采用葡萄糖氧化酶法;空腹胰岛素采用放射免疫法测定。肥胖大鼠出现代谢紊乱后,给予ACT-335827处理,检测大鼠体重、血压、脂肪、甘油三酯、总胆固醇、高密度脂蛋白、低密度脂蛋白、游离脂肪酸(NEFA)、瘦素、空腹血糖及空腹胰岛素等的变化。结果:与普通饮食组相比,经过10周高脂饮食,高脂饮食组大鼠体重显著升高(P0.05),给予ACT-335827处理后,普通大鼠的体重、血压、脂肪含量、脂代谢等均无明显变化;与高脂饮食和高脂饮食加生理盐水处理组大鼠比较,高脂饮食加ACT-335827处理组肥胖大鼠的体重显著下降(P0.05),腹部和附睾脂肪含量下降(P0.05),低密度脂蛋白、甘油三酯、总胆固醇、瘦素水平下降(P0.05),空腹血糖及空腹胰岛素也显著降低(P0.05),但血压、肠系膜脂肪和肩胛棕色脂肪、高密度脂蛋白和NEFA无明显变化(P0.05)。结论:ACT-335827对肥胖大鼠的代谢紊乱具有改善作用,对肥胖大鼠有一定的减肥作用。     

P66Shc mediates increased platelet activation and aggregation in hypercholesterolemia

Background and hypothesis

Hypercholesterolemia leads to a prothrombotic phenotype. Platelet hyperactivity associated with hypercholesterolemia has been attributed, in part, to oxidative stress. P66Shc is a well-known determinant of cellular and organismal oxidative stress. However, its role in platelet biology is not known. We hypothesized that p66Shc mediates platelet hyperactivation and hyperaggregation in hypercholesterolemia.

Methods and results

P66Shc was expressed in both human and mouse platelets, as determined by qRT-PCR and immunoblotting. Mouse platelet p66Shc expression was upregulated by hypercholesterolemia induced by high-fat diet feeding. Compared to wild-type mice, high-fat diet-induced p66Shc expression in platelets was suppressed in transgenic mice expressing a short hairpin RNA targeting p66Shc (p66ShcRNAi). High-fat diet feeding of wild-type mice amplified surface P-selectin expression on platelets stimulated by the thrombin receptor agonist protease-activated receptor-4 (PAR4), and increased aggregation of platelets induced by thrombin. These exaggerated platelet responses induced by high-fat diet feeding were significantly blunted in p66ShcRNAi mice. Finally, thrombin-stimulated platelet reactive oxygen species were suppressed in p66ShcRNAi mice.

Conclusions

Hypercholesterolemia stimulates p66Shc expression in platelets, promoting platelet oxidative stress, hyperreactivity and hyperaggregation via p66Shc.     

二氢杨梅素对高脂饮食诱导的小鼠肥胖的影响及其机制

目的:观察二氢杨梅素(DHM)对高脂饮食诱导小鼠肥胖的影响,并探讨其作用机制是否与促进WAT棕色化有关。方法:60只c57bl/6j小鼠随机分为6组(n=10):①正常对照组(ND组):普通饲料喂养、②正常对照+低剂量DHM组(ND+L-DHM组):普通饲料喂养同时用低剂量DHM(125 mg/(kg·d))处理、③正常对照+高剂量DHM组(ND+H-DHM组):普通饲料喂养同时用高剂量DHM(250 mg/(kg·d))处理、④高脂饮食组(HFD):高脂饲料喂养、⑤高脂饮食+低剂量DHM组(HFD+L-DHM组):高脂饲料喂养同时用低剂量DHM处理、⑥高脂饮食+高剂量DHM组(HFD+H-DHM组):高脂饲料喂养同时用高剂量DHM处理。16周后小鼠空腹过夜,取血测空腹血糖和血脂,随后处死动物,测体长,算出Lee's指数;取肩胛下、腹股沟和附睾处脂肪组织称重后,甲醛固定、HE染色观察脂肪细胞大小,免疫组化检测解偶联蛋白1(UCP1)的表达;实验期间每4周测一次小鼠体重。结果:与ND组相比较,HFD组小鼠体重显著升高,提示肥胖小鼠模型复制成功。此外,HFD组小鼠体脂重量、脂肪细胞直径、Lee's指数和血糖显著增加、脂肪细胞UCP1的表达升高;使用L-DHM和H-DHM处理HFD小鼠后,体脂重量、脂肪细胞直径、Lee's指数和血糖等指标显著逆转,而脂肪细胞UCP1的表达升高更为显著;但L-DHM和H-DHM对正常小鼠上述指标无显著影响。结论:二氢杨梅素抑制高脂饮食诱导的小鼠肥胖,其机制可能与促进WAT棕色化有关。