肝脂复煎剂对实验性脂肪肝的治疗效应

[目的]探讨肝脂复煎剂对实验性脂肪肝的治疗作用.[方法]通过高脂饮食饲养制备大鼠脂肪肝模型;肝脏病理切片证实造模成功.造模大鼠40只随机分为5组,肝脂复低、中、高剂量治疗组,饮食治疗组及模型对照组.分别检测各组大鼠的肝指数(肝重/体重)、肝功能、血脂、血糖、肝脂、血清和肝组织中丙二醛(MDA)及肝组织学改变.[结果]肝脂复煎剂组血脂改善、肝脂显著降低(P＜0.05,＜0.01),血清和肝组织中丙二醛(MDA)显著降低(P＜0.05,＜0.01),肝组织学接近正常.饮食治疗组改善不大.[结论]肝脂复煎剂可有效地用于实验性脂肪肝的治疗.     

短链脂肪酸对高脂饮食诱导肥胖小鼠糖脂代谢紊乱的影响

目的探讨短链脂肪酸(SCFA)对高脂饮食(HFD)诱导的肥胖小鼠糖脂代谢紊乱的影响,并从肠上皮屏障功能角度初步探讨可能的作用机制。方法C57BL/6J小鼠40只,随机分为正常饲料对照组(ND)、高脂饮食模型组(HFD)、短链脂肪酸治疗组(HFD+SCFA)组、乳果糖(LA)治疗对照组(HFD+LA),每组10只,高脂饮食造模共14周,第11周开始给药,给药4周后取材。观察体质量、进食量、肝重、肝体比、附睾后脂肪组织脂肪细胞形态及直径;空腹葡萄糖(FBG),空腹血清胰岛素(FINS)及胰岛素抵抗指数(HOMA-IR);血清三酰甘油(TG)、总胆固醇(TC)、低密度脂蛋白(LDL-C);肝组织TG、血清ALT、AST,肝组织病理以及结肠组织病理改变。结果高脂饮食诱导肥胖小鼠给予SCFA干预4周后,体质量、肝重、肝体比、附睾后脂肪细胞直径、FBG、FSI、HOMA-IR、血清TG、血清TC较HFD组均显著降低(P0.01),且SCFA降低FSI、HOMA-IR、血清TG及TC的作用均优于LA(P0.01或P0.05);与HFD组相比,HFD+SCFA组小鼠肝组织TG含量、血清ALT、AST活性均显著降低(P0.01),肝组织脂肪变性、炎症以及气球样变有显著改善,肝脏活动度积分(NAS)显著降低(P0.01);SCFA干预可显著改善高脂饮食诱导的小鼠结肠上皮损伤、腺体排列紊乱、炎症细胞浸润等病理学改变。结论短链脂肪酸可有效降低高脂饮食诱导肥胖小鼠的体质量、改善血糖血脂代谢紊乱以及脂肪肝;降低肠道炎性反应,提高肠上皮屏障功能是可能的作用机制之一。     

高脂饮食对老年大鼠氧化应激及脂质代谢的影响

目的探讨高脂饮食对老年大鼠氧化应激及其脂质代谢的影响。方法将4～5月龄(青年)和20～22月龄(老年)大鼠随机分为老年对照组(NC2)和老年高脂组(HF2);青年对照组(NC1)和青年高脂组(HF1),分别用不同饮食喂养大鼠8w,测定大鼠血清空腹血糖(FPG)、胰岛素(FINS)、甘油三酯(TG)、总胆固醇(TC)、游离脂肪酸(FFA),血清及肝组织内超氧化物歧化酶(SOD)活力和丙二醛(MDA)、谷胱甘肽(GSM)含量。结果老年对照组与青年对照组相比体重(BM)、TC、TG、FFA、FPG、FINS、MDA升高(P≤0.05或P≤0.01),SOD、GSM、ISI降低;不论是老年大鼠还是青年大鼠,高脂组胰岛素敏感指数低于对照组(P≤0.01),TG、TC、FFA升高,血清及肝组织中SOD的活力减低,GSM含量降低,而MDA的含量升高(P≤0.05或P≤0.01)。结论健康大鼠随月龄增加血脂水平升高,氧化应激反应性降低;相同的高脂饮食情况下老年大鼠对脂代谢的调节能力下降,出现血脂紊乱。     

脂酶对实验性高脂血症性急性坏死性胰腺炎的影响

目的 探讨脂蛋白脂酶(LPL)和肝脂酶(HL)对实验性高脂血症性急性坏死性胰腺炎(HLANP)的影响.方法 通过高脂饲料喂养4周,胆胰管内逆行注射5%牛磺胆酸钠溶液诱导大鼠HLANP模型.72只大鼠按数字随机法分为HLANP组和急性坏死性胰腺炎(ANP)对照组,每组又分为造模后0、3、6、12、24、48 h 6个时间点,每个时间点6只.榆测血清淀粉酶、胆固醇、三酰甘油(TG)、游离脂肪酸(FFA)、LPL和HL水平;观察胰腺组织病理学和超微结构改变;RT-PCR检测胰腺HL mRNA表达;免疫组化方法检测胰腺HL蛋白表达.结果 HLANP组和对照组大鼠血清淀粉酶在12 h达峰值,均值分别为7 176 U/L和6 366 U/L,较基础水平显著升高(P<0.05);HLANP组0～12 h的血清胆固醇水平均高于相应时问点的对照组(P<0.05或P<0.01),TG仅0 h点两组相差显著(P<0.05),分别为(1.19±0.49)mmoi/L和(0.32±0.14)mmol/L;HLANP组FFA水平与对照组无显著差异;HLANP3 h组大鼠血清LPL和HL活性分别为(17.5±7)U/L和(18.6±3.9)U/L,显著高于对照组的(8.9±3.4)U/L和(9.5±2.1)U/L(P<0.05).HLANP组大鼠3、6、24、48 h的胰腺组织坏死程度均显著高于同时点对照组(P<0.05);HLANP组大鼠胰腺腺泡细胞出现脂滴沉积、粗而内质网扩张、酶原颗粒减少和线粒体肿胀.HLANP 3、6 h组大鼠胰腺HL mRNA表达分别为1.1±0.09和0.89±0.08,均显著高十对照组的0.1l 4-0.01和0.15±0.03(P<0.05);HLANP组和对照组大鼠胰腺腺泡细胞在ANP前未见HL蛋白表达,诱导ANP后均可见HL蛋白强阳性表达.结论 HIANP大鼠脂酶(LPL和HL)的表达增高,其血清蛋白含量增高,导致脂质分解,加重ANP.LPL和HL可能是加重HLANP的最关键的脂质代谢酶之一.     

载脂蛋白A5在贝特类药物调脂治疗中的作用机制研究

目的 研究载脂蛋白A5(ApoA5)在贝特类药物调脂中的作用.方法 雄性Wistar大鼠随机分4组,取血和肝匀浆检测血脂指标,应用RT-PCR法检测肝脏ApoA5及过氧化物酶体增殖物激活型受体α(PPAR-α)mRNA表达情况,比较ApoA5与各指标间的相关性.结果 ①血清及肝匀浆甘油三酯(TG)高脂组及非诺贝特低剂量组明显高于正常对照组(P＜0.01,P＜0.05);非诺贝特高、低剂量组明显低于高脂组(P＜0.01);非诺贝特高、低剂量组间有显著差异(P＜0.05);②ApoA5和PPAR-α表达正常对照组明显高于高脂组、非诺贝特低剂量组(P＜0.01);高脂组明显低于非诺贝特高、低剂量组(P＜0.01);非诺贝特高、低剂量组间有显著差异(P＜0.01).③ApoA5mRNA表达与TG呈明显负相关(P＜0.01),与PPAR-α表达呈正相关(P＜0.01).ApoA5与总胆固醇(TC)无明显相关性.结论 ApoA5可能是影响血浆TG代谢的重要因素,贝特类药物上调ApoA5和PPAR-α基因表达,与剂量相关.ApoA5在贝特类药物调脂作用可能是通过PPAR-α为作用靶点调控ApoA5发挥降TG作用.     

Ghrelin对高脂喂养大鼠肝脏氧化应激及Akt/GSK3β信号通路的影响

目的探讨Ghrelin对高脂喂养的大鼠肝脏氧化应激水平及Akt/GSK3β信号通路的影响。方法成年雄性Wistar大鼠随机分为正常对照组(NC组)、高脂饮食组(HFD组)和Ghrelin组,每组10只小鼠。NC组给予正常饲料喂养,HFD组及Ghrelin组给予高脂饮食,喂养6周后,进行药物干预4周:Ghrelin组给予Ghrelin(60μg/kg)每日两次腹腔注射,相应NC组及HFD组给予0.9%氯化钠溶液进行对照;结束后处死大鼠,检测血清丙氨酸氨基转移酶(ALT)、三酰甘油(TG)及总胆固醇(TC);测定肝组织匀浆超氧化物歧化酶(SOD)及丙二醛(MDA);实时PCR检测肝脏组织Akt、GSK3βmRNA表达的改变。结果 Ghrelin组大鼠肝脏湿重、血TC及TG均低于HFD组(P0.05);Ghrelin组与HFD组比较,SOD明显增高(P0.05),MDA有所降低(P0.05);Ghrelin组与HFD组相比,肝脏组织Akt基因mRNA表达升高1.03倍(P0.05),GSK3β基因mRNA表达升高3.23倍,(P0.05)。结论 Ghrelin能改善高脂喂养大鼠血脂水平,减轻氧化应激损伤,其作用机制可能与Akt/GSK3β信号通路相关。     

模拟代谢性内毒素血症对肝损伤小鼠肝组织TLR4信号通路的影响

目的：观察持续4 w的模拟代谢性内毒素血症对小鼠肝脏组织病理和4型Toll样受体（TLR4）信号通路的影响。方法将30只雄性C57BL/6J 小鼠随机分为正常组（n=10）和内毒素组（n=10）,均予以普通饲料喂养,和高脂组（n=10）,予以高脂饲料喂养。内毒素组小鼠同时经腹部皮下植入的微泵注入内毒素300μg·kg-1·d-1,连续4 w,正常组小鼠皮下微泵持续注入生理盐水作为对照。4 w后测定小鼠血清内毒素水平,对肝组织切片行HE染色后进行非酒精性脂肪性肝病评分（NAS）,采样Real time PCR法测定小鼠肝组织TLR4及其下游的MyD88和TRIF-related adaptor molecule （TRAM） mRNA水平。结果内毒素组小鼠血清内毒素水平（0.62±0.04 EU/ml）显著高于正常组（0.50±0.06 EU/ml,P〈0.05）和高脂组（0.49±0.05 EU/ml,P〈0.05）;内毒素组小鼠肝组织主要表现为单纯性脂肪变性,NAS积分为（2.30±0.49）,高脂组小鼠肝组织炎症较明显,NAS积分为（4.20±1.61）,显著高于内毒素组（P〈0.05）;与正常组相比,内毒素组小鼠肝组织TLR4 mRNA 水平上调5.12倍（P＜0.01）,TRAM mRNA水平上调3.46倍（P＜0.01）,而MyD88 mRNA水平与正常组比,无显著差别。结论持续4 w的模拟代谢性内毒素血症可诱导小鼠肝脏单纯性脂肪变性,TLR4 mRNA 和TRAM mRNA水平上调,而MyD88 mRNA水平无显著变化。     

脂肝康胶囊治疗酒精性肝病的临床研究

目的:探讨中药脂肝康对酒精性肝病(ALD)的防治作用及机制.方法:选择酒精性肝病65例随机分为治疗组33例,对照组32例,治疗组在与对照组护肝治疗的基础上应用脂肝康胶囊10克/次,3次/d,90天为1个疗程.对比观察两组患者症状体征变化,以及肝功能、血脂水平、肝脂酶(HL)、脂蛋白脂肪酶(LPL)活性、超氧化物岐化酶(SOD)、脂质过氧化物(LPO)、肝纤维化血清标志物--透明质酸(HA)、Ⅲ型前胶原(PCⅢ)等检测指标和肝脏影像学、组织学变化.结果:治疗结束后,治疗组患者肝区痛、腹胀、肝肿大及肝脏B超显示脂肪肝影像消失或明显改善.TG(甘油三酯)、LPO、HA、PCⅢ、肝功能正常或接近正常,SOD值回升、HL、LPL活性增高与血脂水平呈负相关,与对照组比较差异有显著性意义(P＜0.05或P＜0.01).结论:脂肝康可通过促乙醇、脂质代谢,抑制乙醇代谢过程中致肝损伤因子的形成,改善微循环,促进肝组织修复,抑制肝纤维化形成,对ALD有较好的疗效,总有效率达96.96%.     

脂联素及其受体在脂肪肝病理机制中的意义及中药干预作用

目的 研究脂联素(ADP)及其脂联素受体 2 (AdipoR2)在脂肪肝病理变化中的意义及中药的干预作用. 方法采用单纯高脂饮食(高脂模型组)和四氯化碳皮下注射复合高脂低蛋白饮食诱导(复合模型组)的两组大鼠脂肪肝模型,各随机分为正常组、模型组和中药干预组.高脂模型组大鼠造模10周,其中药组在第7周起予以中药(祛湿化瘀方)灌胃干预4周;复合模型组大鼠造模4周,其中药组在第3周起予中药干预2周.观察项目:(1)肝组织HE染色,观察各组大鼠肝脂肪变性程度变化;(2)肝组织甘油三酯(TG)、游离脂肪酸(FFA)、AdipoR2含量及血清ADP含量;(3)肝组织TG、FFA、AdipoR2、血清ADP含量间的相关性分析.数据均使用SPSS12.0软件包进行统计学分析.组间比较采用单因素方差分析S-N-K检验(q检验).等级资料用Ridit分析.相关分析采用Bivariate相关分析.结果 (1)在两个模型大鼠实验中,模型组肝组织均出现严重的脂肪变性,肝组织TG、FFA含量均显著升高,高脂模型组分别达正常组的3.2倍和3.5倍,q值分别为16.00和8.10,p值均<0.01;复合模型组分别达正常组的3.8倍和3.6倍,q值分别为10.10和10.87,P值均<0.01.血清ADP与肝组织AdipoR2均显著降低,高脂模型组分别为正常组的56.1%和56.0%,q值分别为10.19和9.03,P值均<0.01;复合模型组分别达正常组的55.6%和71.1%,q值分别为5.48和7.16,P值均<0.01;在两个模型中,中药干预组的TG,FFA含量显著低于模型组,ADP、AdipoR2含量显著高于模型组.(2)肝脏TG、FFA含量与血清ADP含量、肝组织AdipoR2含量之间均呈显著负相关.结论 (1)血清ADP和肝AdipoR2水平均显著低下,在脂肪肝病理机制中有重要意义.(2) 中药祛湿化瘀方可显著提高脂肪肝大鼠的ADP、AdipoR2水平,这可能为该方防治脂肪肝作用的重要药理环节.     

壳脂胶囊对非酒精性脂肪性肝炎大鼠肝组织PPAR-γ、IR的作用研究

[目的]探讨壳脂胶囊对非酒精性脂肪性肝炎大鼠肝组织PPAR-γ、IR的影响.[方法]高脂饮食饲喂SD大鼠以制备非酒精性脂肪性肝炎模型,造模同时进行药物干预.干预8周后,自动生化分析仪检测血清谷草转氨酶（AST）、谷丙转氨酶（ALT）、总胆固醇（CHO）、低密度脂蛋白（LDL）、高密度脂蛋白（HDL）、甘油三酯（TG）水平,苏木精-伊红染色、油红O染色观察肝组织病理,RT-PCR检测PPAR-γmRNA和IR mRNA,Western-blot检测PPAR-γ和IR蛋白表达.[结果]与模型组比较,壳脂胶囊能明显降低血清TG、CHO、LDL、AST、ALT水平（P＜0.01）;壳脂胶囊组脂肪变性和炎症反应程度均较模型组有一定的减轻;壳脂胶囊组大鼠PPAR-γ和IR的蛋白和基因表达水平均高于模型组（P＜0.05）.[结论]壳脂胶囊可能通过上调肝组织PPAR-γ、IR蛋白及PPAR-γ mR-NA、IR mRNA的表达,改善胰岛素抵抗,进而调解脂肪代谢,改善肝脏功能,达到防治NASH的目的.     

四逆汤对高胆固醇喂饲所致动脉粥样硬化形成和氧化损伤的影响

为了观察四逆汤对高胆固醇喂饲所致家兔实验性动脉粥样硬化形成和氧化损伤的影响，采用高胆固醇喂饲模型；将24只新西兰家兔随机分为3组：正常组、模型组、四逆汤组，分别给予普通饲料(正常对照组)和高胆固醇饮食(其它2组)喂养，四逆汤组另加用四逆汤方药；实验结束后，观察血管病理变化、血和血管超氧化物歧化酶活性、血浆和血管丙二醛含量、超氧化物歧化酶蛋白和基因表达。结果发现，与模型组相比，四逆汤组主动脉脂质斑块面积、内膜斑块面积和厚度明显降低；血和血管超氧化物歧化酶活性明显增加；血浆和血管丙二醛的含量明显增加；血管超氧化物歧化酶蛋白和基因表达明显增强。研究结果提示，四逆汤具有较好的抗动脉粥样硬化作用，抗氧化损伤可能是四逆汤产生抗动脉粥样硬化作用的重要机制之一。     

熊去氧胆酸对高脂饮食大鼠脂肪性肝炎形成的影响

目的 探讨熊去氧胆酸对高脂馀食诱发的大鼠非酒精性脂肪性肝炎模型形成的影响。方法 29只SD大鼠随机分为3组：模型组予高脂饮食饲养;治疗组在高脂饮食饲养2周后同时加用熊去氧胆酸;正常组予标准饮食饲养,12周处死,结果 所有造模大鼠均出现肥胖、高脂血症和血清转氨酶升高,伴典型的脂肪性肝炎;与模型组相比,治疗组仅血清转氨酶、肝组织脂肪变和炎症坏死等指标有改善趋势,但两组间并无统计学差异。结论 熊去氧胆酸对高脂饮食诱发的肥胖、高脂血症性脂肪性肝炎可能并无防治作用。     

高脂高糖诱导的非酒精性脂肪肝小鼠肝胰岛素底物受体-2的表达

目的探讨非酒精性脂肪肝小鼠肝脏胰岛素受体底物-2(insulin receptor substrate-2,IRS-2)的表达。方法于2002年1月至2003年3月在中国医科大学附属盛京医院内分泌科将30只6~8周龄的雌性SPF级C57BL6J小鼠随机分为3组饲养,其中正常饮食组10只、高脂高糖饮食8周组10只(实验过程中死亡5只)及高脂高糖食16周组10只。测定其血脂、血清胰岛素及空腹血糖、肝功能、肝脏重量、腹部瘦肉及瘦肉含量,肝脏脂质含量及IRS-2蛋白表达。并做肝脏病理检查。结果高脂高糖饮食16周的小鼠腹部脂肪量、血清甘油三酯、空腹血糖、碱性磷酸酶显著高于正常饮食小鼠(P<0.05~0.01);白蛋白及白蛋白球蛋白比值较正常饮食小鼠显著降低(P<0.05)。高脂高糖饮食小鼠肝脏有明显脂肪变性,16周的小鼠较8周的小鼠严重。高脂高糖饮食小鼠的肝脏总胆固醇和甘油三酯含量显著高于正常饮食小鼠,16周时达到正常饮食小鼠的2倍以上;IRS-2表达低于正常饮食小鼠,16周的小鼠高于8周的。结论高脂高糖饮食可使C57BL6J小鼠出现非酒精性脂肪肝,肝脏的IRS-2蛋白表达量低于正常饮食小鼠     

祛湿化瘀方对高脂饮食诱导的小鼠非酒精性脂肪性肝炎的防治作用

目的：观察祛湿化瘀方治疗非酒精性脂肪性肝炎（NASH）的药效。方法：12周龄C57BL／6J雄性小鼠32只．SPF级。随机分为对照饮食组（n=16）和高脂饮食组（n：16）,对照饮食组小鼠给予10％热能来源于脂肪的对照饲料,高脂饮食组小鼠给予60％热能来源于脂肪的高脂饲料。12周末,对照饮食组和高脂饮食组再分,51j随机分为正常组（N,n=8）、正常给祛湿化瘀方组（NQ,n=8）、模型组（M,n=8）、模型给祛湿化瘀方组（Q,n=8）,分别以lml／100g鼠重灌胃给予祛湿化瘀方（生药含量0．93g／m1）和灭菌饮用水,16周末取材,观察各组小鼠体重、肝组织TG、血清ALT、肝组织HE染色、油红O染色等指标的变化。结果：模型组小鼠体重明显增加,肝组织甘油三酯（TG）含量、血清丙氨酸转氨酶（ALT）明显升高,肝脏HE染色见肝细胞明显的肿胀、脂肪变性和炎细胞浸润．油红O染色见肝脏显著脂滴沉着。肝脏脂肪变积分、炎症积分、气球样变积分均显著升高,并达脂肪性肝炎诊断标准。祛湿化瘀方组小鼠肝组织TG、血清ALT较模型组显著下降,同时肝脏病理组织变化改善,病理积分较模型组显著降低。结论：祛湿化瘀方能够有效防治高脂饮食诱导的C57BL／6J小鼠NASH。     

Effects of dietary fish oil and butterfat on serum lipids and monocyte and platelet interactions with aortic endothelial cells

We studied effects of dietary lipids on some of the initial events in atherogenesis. Adult swine were fed low fat/low cholesterol diets, then challenged with a high cholesterol (1%, w/w) diet supplemented with 11.5% (w/w) butterfat (BF) or MaxEPA^TM fish oil (FO). Serum lipids and monocyte and platelet adhesion to porcine aortic endothelial cells in vitro were measured during feeding of the low fat diet and at 1, 2, and 5 weeks after the dietary challenge. Total cholesterol increased significantly in animals fed the BF and FO diets, but there was no difference between the groups. Animals fed FO had total cholesterol/high-density lipoprotein cholesterol values twice those fed BF ( ). After 2 weeks on the hypercholesterolemic diet, monocyte adhesion to endothelial cells increased in swine fed FO by 123% above those fed a low fat diet, and adhesion values remained elevated (56% above baseline value) after 5 weeks. Monocytes from swine fed BF showed increased adhesion by 87, 53, and 14% above those fed the low fat diet at 1, 2, and 5 weeks respectively. Platelet adhesion to endothelial cells decreased (P < 0.05) after diet change and remained low. Adhesion of platelets from swine fed FO was significantly lower than those fed BF at 1 and 2 weeks but higher at 5 weeks. The FO diet, compared to the BF diet, produced a more atherogenic cholesterol profile and greater monocyte adhesion to endothelial cells, conditions which in vivo may promote lesion initiation.     

Doxycycline affects diet- and bacteria-associated atherosclerosis in an ApoE heterozygote murine model: cytokine profiling implications

BACKGROUND: It has been postulated that systemic infection with pathogens such as Porphyromonas gingivalis (Pg) elevates the inflammatory response and increases susceptibility to atherosclerosis. We hypothesized that Doxycycline would be beneficial in diet- and/or Pg-induced atherosclerosis given its role in various cell functions and matrix remodeling. METHODS AND RESULTS: ApoE+/- mice were inoculated weekly with Pg and treated with either Doxycycline or saline; animals were fed either a high-fat or chow diet. Animals were euthanized at 14 or 24 weeks and histomorphometric analysis of atheromatous lesions in proximal aorta, levels of SAA and serum cytokine profiling were performed. Histomorphometric analysis demonstrated that in non-infected mice fed a high fat diet, Doxycycline treatment resulted in a reduction of mean lesions from 10.5%+/-.49 to 1.09%+/-0.102 (p<0.05) at 14 weeks and a reduction from 21.5%+/-6.49 to 8.26%+/-0.162 (p=0.106) at 24 weeks. Chow-fed Pg mice treated with Doxyclycline also resulted in a reduction from 0.62%+/-0.128 to 0.0%+/-0.0 (p<0.05) at 14 weeks and a reduction from 0.92%+/-0.23 to 0.0%+/-0.0 (p<0.05) at 24 weeks. Administration of Doxycycline to mice fed a high fat diet and Pg-inoculated resulted in a reduction of mean percentage of atheromatous lesions from 16.46%+/-1.69 to 1.141%+/-0.23 (p<0.05) at 14 weeks and a reduction from 25.27%+/-1.734 to 0.428%+/-0.033 (p<0.05) at 24 weeks. At this timepoint, SAA levels in Pg-infected animals were reduced by five-fold and three-fold in Doxycycline-treated chow and high fat-diet groups, respectively. Cytokine antibody arrays revealed a marked reduction in the levels of pro-inflammatory cytokines in Doxycycline-treated groups whether Pg-infected or fed a high fat diet while anti-inflammatory cytokines were not affected. Consistent with the role of Doxycycline on matrix proteases, at 24 weeks MMP-9 Serum levels were markedly reduced by 60% (p<0.05) and 30% (p<0.05) with Doxycycline treatment in Pg-infected high fat and chow diet groups, respectively. CONCLUSIONS: Doxycycline decreases pro-inflammatory cytokines and results in reduction of atherosclerosis in ApoE+/-Pg-inoculated and/or high fat diet fed mice.     

烟酸对实验性动脉粥样硬化兔脂肪组织和细胞Caveolin-1表达的影响

目的 探讨烟酸对实验性动脉粥样硬化兔脂肪组织和细胞小凹蛋白1(Caveolin-1)表达的影响.方法 16只健康雄性新西兰大白兔给予高脂饮食8周,随机分为高脂组(继续饲以高脂饲料6周,n=8)和烟酸组[在高脂饮食基础上给予烟酸200 mg/(kg·d),共6周,n=8],另选8只兔给予普通饮食14周作为正常对照组.实验前后测定血脂和体重,14周末处死动物,取腹股沟皮下脂肪组织采用实时荧光定量PCR检测Caveolin-1 mRNA表达.体外观察不同浓度烟酸(0、0.2、1.0和5.0 mmol/L)对兔脂肪细胞Caveolin-1 mRNA表达的影响.结果 与正常对照组相比,高脂组总胆固醇、甘油三酯和低密度脂蛋白胆固醇水平均明显升高,主动脉内膜厚度和斑块面积均显著增加,而脂肪组织Caveolin-1 mRNA表达明显降低;与高脂组相比,烟酸组总胆固醇、甘油三酯和低密度脂蛋白胆固醇水平均明显降低,高密度脂蛋白胆固醇水平升高,且主动脉内膜厚度和斑块面积均显著缩小,脂肪组织Caveolin-1 mRNA表达升高.体外实验显示,烟酸可呈浓度依赖性地刺激脂肪细胞Caveolin-1 mRNA表达.结论 烟酸可明显改善血脂谱及稳定动脉粥样斑块,可能与上调脂肪组织或细胞Caveolin-1 mRNA表达水平有关.     

A diet high in fat stimulates adipocyte proliferation in older (22 month) rats

The effect of a high fat diet in stimulating adipocyte proliferation, as measured by the incorporation of [3H]-thymidine into fat cell DNA, was studied in 22-month-old female Sprague-Dawley rats. Rats were fed a low fat (n = 10) or a high fat diet (n = 9) for a total of six days. On days 4 and 5 of dietary manipulation, rats were injected with 80 microCi/100 g body weight of [3H]-thymidine. Rats were continued on their respective diets for one more day, starved for 72 h and then refed a stock diet for three weeks in order to increase turnover of stroma cells, thus diluting the specific activity of stromal DNA with minimal effect on specific activity of fat cell DNA. The diet groups did not differ significantly with respect to body masses, food intake, parametrial (PARA) and retroperitoneal (RP) depot masses, cell number or cell size. The specific activity of DNA in both PARA and RP depots was greater in the adipocyte than in the stromavascular fraction. Specific activity of fat cells was significantly greater from rats fed the high fat than the low fat diet in both PARA and RP depots. Radioautography of adipose tissue confirmed that there was a greater percentage of adipocyte nuclei labeled in the rats fed the high fat diet. Also, there were few labeled nuclei found in stroma cells. In conclusion, older female rats increased adipocyte proliferation when fed a high fat diet.     

Effect of high fat diet on body weight and mammary tumor latency in MMTV-TGF-alpha mice

OBJECTIVE: The role of high fat diets in breast cancer/mammary tumor (MT) development is controversial. This may be partially attributable to variable effects of high fat diets on body weight. Here, we used a moderately high fat diet (32.5% fat calories) expected to cause obesity in most mice, but predicted to result in some mice remaining in the weight range of mice fed the low fat diet (11% fat calories). This provided the opportunity to compare mice fed the high fat diet exhibiting different body weights and mice of similar weight consuming high vs low fat diets. EXPERIMENTAL METHODS: Transgenic MMTV-TGF-alpha mice, a model of postmenopausal breast cancer, consumed a low fat diet, that is, chow-fed (n=25) or a moderately high fat diet from 10 weeks of age (n=51). Body weight at 34 weeks of age was used to assign high fat diet mice to obesity-prone>overweight>obesity-resistant groups (n=17) (P<0.0001). Mice were euthanized when MTs developed or at 85 weeks of age. RESULTS: Final body weights were highest in obesity-prone>overweight >obesity-resistant=chow-fed mice. Fat pads and fat pad:carcass were heaviest in obesity-prone followed by overweight mice. However, obesity-resistant mice had fat pad weights and fat pad:carcass three-fold greater than chow-fed mice. All groups had MT incidences between 72 and 82%. Obesity-prone mice exhibited the shortest MT latency (P<0.0001), but obesity-resistant mice had significantly shorter latency than chow-fed mice. CONCLUSIONS: Consumption of a high fat diet increased adiposity and shortened MT latency in relation to its effect on body weight. These results indicate a complex role of dietary fat level on mammary tumorigenesis.