二甲双胍干预高脂饲养所致大鼠脂肪肝的研究

目的 探讨二甲双胍对实验性脂肪肝的治疗作用。方法 通过12周高脂饲料喂养制备大鼠实验性脂肪肝模型；肝脏病理切片证实造模成功后，取24只造模大鼠随机分为3组并给予相应处理：二甲双胍组给予二甲双胍l56mg／kg灌胃，1次／d；饮食治疗组及模型对照组等容积蒸馏水灌胃；除模型对照组外，其余各组均进食普通饲料。4周后分别检测各组动物的肝功能、血脂、血糖、肝脂质、肝指数胰岛素抵抗指数及肝组织学改变。结果二甲双胍能显著降低血脂、肝脂，改善肝功能；而饮食治疗使肝组织学有一定改善，但肝酶活性、血清甘油三酯和胆固醇增高持续存在。结论 二甲双胍可有效地用于实验性脂肪肝的治疗。     

高脂饮食诱导幼龄大鼠肝脂肪性变和胰岛素抵抗的发生及二甲双胍的干预作用

目的 通过高脂饮食诱导幼龄大鼠建立非酒精性脂肪性肝病（NAFLD）伴胰岛素抵抗模型,探讨NAFLD幼鼠胰岛素抵抗的发生机制及二甲双胍的干预疗效.方法 将60只3周龄刚离乳雄性SD大鼠按随机数字表法分为3组：对照组、高脂组及二甲双胍组（高脂＋二甲双胍）,每组各20只.对照组予普通饮食,高脂组和二甲双胍组给予高脂饮食5周,同时对照组和高脂组给予生理盐水灌胃,二甲双胍组给予二甲双胍混悬液灌胃（0.25 g·kg-1·d-1）.第5周末从各组大鼠中随机选取12只进行正常血糖-高胰岛素钳夹试验,评价胰岛素敏感性;另8只大鼠处死并取新鲜肝组织进行肝组织病理形态和脂质沉积观察,其中随机取6只通过实时荧光定量PCR分析肝组织中固醇调节元件结合蛋白-1（SREBP-1）、胰岛素受体（IR）、胰岛素样生长因子-1（IGF-1）mRNA的表达.组织学分级差异比较采用秩和检验进行分析.其他指标采用单因素ANOVA分析,两两比较采用LSD法.结果 实验5周后：（1）体重：对照组[（316±17）g]、高脂组[（202±21）g]、二甲双胍组[（171±19）g],3组间两两比较差异有统计学意义（P＜0.01）.（2）病理结果：高脂组大鼠肝脏符合典型的NAFLD病理特征.（3）葡萄糖输注率高脂组、对照组、二甲双胍组分别为（6.51±1.52）、（11.57±1.97）、（13.08±2.33）mg·kg-1·min-1.（4）与对照组相比,高脂组肝组织SREBP-1 mRNA表达较高[0.85±0.10比1.67±0.28,P＜0.05],IR mRNA[（1.16±0.22）比（0.56±0.22）,P＜0.01]、IGF-1 mRNA[（0.87±0.14）比（0.26±0.14）,P＜0.01]表达较低;高脂组与二甲双胍组肝组织SREBP-1 mRNA、IR mRNA、IGF-1 mRNA比较差异无统计学意义（P＞0.05）.结论 高脂饲养5周可建立幼龄SD大鼠NAFLD并发胰岛素抵抗模型,二甲双胍预防可提高机体胰岛素敏感性,其减少NAFLD幼鼠体重的作用与幼鼠体重是否超标可能无关.     

二甲双胍对糖尿病大鼠血糖、血脂水平及骨骼肌GLUT4表达的影响

雄性SD大鼠55只,分别予普通饲料和高糖高脂饲料(二甲双胍组)喂养。高糖高脂饲料饲养联合STZ(40 mg/kg)构建糖尿病大鼠模型。二甲双胍组予灌胃4周后检测血糖(FPG)、空腹胰岛素(FINS)、血脂的水平变化,计算稳态模型胰岛素抵抗指数(HOMA-IR)。留取各组大鼠骨骼肌,RT-PCR检测GLUT4 mRNA表达,免疫组化法检测GLUT4蛋白表达。结果与正常对照组比较,糖尿病大鼠模型FPG、FINS、TG、HOMA-IR显著增高(P 0. 05),骨骼肌GLUT4表达显著减少(P0. 05);与模型组比较,二甲双胍组FPG、FINS、HOMA-IR显著降低(P 0. 05),骨骼肌GLUT4表达显著增加(P 0. 05)。结论二甲双胍可降低糖尿病模型大鼠血糖。     

不同药物对肥胖大鼠血清内脏脂肪素水平的影响

目的探讨非诺贝特、二甲双胍、托吡酯对肥胖大鼠脂肪含量及血清内脏脂肪素（Visfatin）水平的影响。方法将高脂饮食造模成功的单纯性肥胖大鼠32只随机分为非诺贝特组[83.4 mg/（kg·d）]、二甲双胍组[400.0mg/（kg·d）]、托吡酯组[53.6 mg/（kg.d）]及空白对照组,每组8只。继续高脂饮食8周后,检测各组大鼠用药前后脂肪含量、血清Visfatin水平和生化指标。结果与空白对照组比较,非诺贝特组、托吡酯组大鼠的摄食量明显减少（P均〈0.01）,体质量明显减轻（P〈0.01或〈0.05）;二甲双胍组大鼠的摄食量虽未受明显影响,体质量却明显减轻（P〈0.05）,且Visfatin水平降低（P〈0.05）。另外,非诺贝特组大鼠体脂含量明显降低（P〈0.01）。结论非诺贝特、二甲双胍及托吡酯均可降低肥胖大鼠的体质量,其中非诺贝特可显著降低肥胖大鼠的脂肪含量,二甲双胍可降低血清Visfatin的水平。     

肥胖糖尿病大鼠血清GLP-1及TNF-α、IL-18关系的研究

雄性大鼠80只,随机选取60只以链脲菌素(STZ)30mg/kg制成糖尿病大鼠模型。令20只正常喂养,为对照组。将成模大鼠随机分为2组:普通饲料喂养组与高脂喂养组,分别给与普通饲料及糖高脂饲料喂养12周后尾静脉采血。测定Lee指数、血脂、总胆固醇(TC)、甘油三脂(TG)、低密度脂蛋白(LDL)、高密度脂蛋白(HDL)。以高脂饲料组Lee指数较普通饲料组显著升高为肥胖糖尿病大鼠成膜。将大鼠分为非肥胖组及肥胖组。给予两组大鼠500g/L葡萄糖按2g/kg体质量灌胃,30分钟后尾静脉采血。应用酶免法(ELISA)方法测定两组大鼠血清GLP-1、IL-18、TNF-α水平及大鼠服糖后30分钟血清GLP-1水平。结果:与对照组相比,肥胖组及非肥胖组血清空腹及糖负荷后GLP-1水平降低、TNF-α、IL-18水平升高(P<0.01)。与非肥胖组相比,肥胖组血清空腹及餐后GLP-1水平降低、TNF-α、IL-18水平升高(P<0.05)。相关分析显示,GLP-1与TNF-α、IL-18、Lee指数、低密度脂蛋白(LDL-C))、餐后血糖具有相关性(P<0.05)。GLP-1水平与IL-18、TNF-α呈负相关(P<0.01)。结论:肥胖降低2型糖尿病大鼠血清GLP-1水平,GLP-1水平的降低可能与IL-18、TNF-α相关。     

二甲双胍对糖尿病大鼠血清同型半胱氨酸水平及肠道菌群的影响

目的 探讨二甲双胍对糖尿病大鼠血清同型半胱氨酸（Hcy）水平及肠道菌群的影响。方法 健康雄性SD大鼠经高糖高脂饲料喂养4周，随机分为正常对照组、二甲双胍组、模型组。二甲双胍组、模型组一次性腹腔注射1%链脲佐菌素溶液35 mg/kg，建立糖尿病模型。二甲双胍组每日给予200 mg/kg二甲双胍溶液灌胃，正常对照组、模型组每日给予等量的双蒸水灌胃，均连续灌胃8周。观察大鼠的进食、饮水、大小便、毛色、活动情况；于干预第1、4、8周末称重，取尾尖血检测血糖；用ELISA法检测血清Hcy，用全自动生化分析仪检测血清TG、TC、HDL-C、LDL-C；用HE染色法观察结肠组织病理变化；采集结肠根部粪便，用16S高通量测序检测肠道菌群，对测序结果进行菌群操作分类单元（OTU）分析及Alpha多样性分析。结果 正常对照组状态良好，模型组有典型糖尿病症状，二甲双胍组糖尿病症状缓解。与正常对照组比较，模型组干预第1、4、8周血糖高（P均<0.05）；与模型组比较，二甲双胍组干预第4、8周血糖低（P均<0.05）。与正常对照组比较，模型组血清Hcy、LDL-C水平高（P均<0.05）；与模...     

大豆异黄酮及羧甲基纤维素钠对去卵巢大鼠体重、血脂的影响

目的 研究大豆异黄酮及羧甲基纤维素钠对去卵巢大鼠肥胖的预防作用以及对血脂的改善作用.方法 清洁级7 w龄SD雌性大鼠88只,随机分为两组,喂饲不同剂量的羧甲基纤维素钠.每组内部再根据体重随机分为6亚组,1亚组为单纯开腹术组,其他5组在无菌条件下切除双侧卵巢,喂饲不同剂量的大豆异黄酮.手术后给与高脂饲料诱导肥胖,实验组同时进行受试物灌胃.结果 大豆异黄酮能显著降低去卵巢大鼠的体重、改善大鼠血脂水平,降低血清中总胆固醇(TC)、甘油三酯(TG)水平,升高高密度脂蛋白胆固醇(HDL-C)水平.羧甲基纤维素钠能显著降低大鼠体重,并与大豆异黄酮具有协同作用,但其对血脂的作用甚微.结论 大豆异黄酮能够预防去卵巢大鼠的肥胖,并且改善血脂;羧甲基纤维素钠可显著减缓大鼠体重的增加,但对血脂水平影响甚微.     

棕色脂肪组织特异性基因在抵抗肥胖中作用的研究

目的通过研究高脂饮食诱导肥胖与肥胖抵抗大鼠肩胛间棕色脂肪组织中UCP-1、PGC-1α、Dio-2的表达情况以及电针刺激对肥胖大鼠UCP-1、PGC-1α表达的影响,探讨棕色脂肪组织特异性基因在抵抗肥胖中的作用。方法 40只雄性SD大鼠,按体重随机分为高脂实验组(n=28)和基础对照组(n=12)。分别给予高脂饲料和基础饲料喂养。高脂饮食5周末,将高脂实验组大鼠体重大于基础对照组最大体重者归为饮食诱导肥胖大鼠(DIO),将高脂实验组大鼠体重低于对照组平均体重者归为饮食诱导肥胖抵抗大鼠(DIO-R)。从DIO随机取6只为肥胖组(n=6)与肥胖抵抗组(n=6)、基础对照组(n=6),比较各组大鼠体重、两种脂肪重水平,使用实时荧光定量PCR及Western blot方法比较三组肩胛间棕色脂肪组织中UCP-1、PGC-1α、Dio-2表达水平的差异。在DIO大鼠中再取10只随机分为:肥胖组(Ob组,n=5)、电针刺激组(EA组,n=5)与基础对照组(n=5)以基础饲料适应性喂养1周后,其中EA组选取足三里、三阴交给予电针刺激,每周3次,每次30 min,观察摄食量及体重变化。6周后使用实时荧光定量PCR及Westernblot方法比较3组大鼠棕色脂肪组织中UCP-1、PGC-1α表达水平的差异。结果 DIO组明显高于DIO-R组,DIO-R组大鼠肩胛间棕色脂肪组织重及Dio-2、PGC-1α、UCP-1mRNA表达水平明显高于DIO大鼠(P<0.05)。高脂组大鼠PGC-1α、Dio-2m RNA表达水平均低于对照组大鼠(P<0.05);DIO-R组大鼠UCP-1 mRNA表达水平高于对照组大鼠(P<0.05)。DIO大鼠UCP-1蛋白水平表达低于基础对照组及DIO-R大鼠(P<0.05)。电针刺激6周后,电针刺激组大鼠棕色脂肪组织中UCP-1、PGC-1αmRNA及蛋白水平表达均高于Ob组及对照组(P<0.05)。电针刺激组大鼠体重、摄食量低于肥胖组大鼠(P<0.05)。结论高脂饮食条件下,SD大鼠表现为明显的肥胖易感性差异。饮食诱导肥胖抵抗大鼠棕色脂肪组织重及特异性基因表达升高。电针刺激增加了棕色脂肪组织特异性基因表达,减少摄食量。棕色脂肪组织特异性基因表达在抵抗肥胖中有重要作用。     

腺苷酸激活蛋白激酶与肥胖大鼠肝脏脂质沉积的关系

目的探讨肥胖大鼠肝脏组织腺苷酸激活蛋白激酶(AMPK)的表达及其对肝脏脂质沉积的影响。方法选用18只刚断乳的SPF级SD雄性大鼠,随机挑选6只普通饲料喂养为正常组,另一组12只高脂饲料喂养,12 w后成功建立肥胖模型大鼠6只。分别检测体重、Lee指数、内脏脂肪、肝湿重等指标。通过油红O染色和检测肝脏甘油三酯(TG)、总胆固醇(TC)含量评估两组大鼠肝脏脂质沉积的情况。采用Western印迹检测大鼠肝脏磷酸化(p)-AMPK/AMPK、p-ACC/ACC水平。结果与正常组大鼠相比,肥胖组大鼠体重与Lee指数、附睾脂肪、肾周脂肪量、肝湿重、肝脏内TG与TC含量均显著升高,油红O染色结果显示肥胖组肝脏脂质沉积较正常组明显增多。Western印迹结果显示,与正常组大鼠比较,肥胖组大鼠肝脏p-AMPK/AMPK和p-ACC/ACC表达明显降低。两组大鼠肝脏组织中p-AMPK、p-ACC表达水平与肝脏TG、TC呈负相关。结论高脂饮食诱导食源性肥胖大鼠可降低AMPK的活性,从而导致肝脏组织TG、TC合成增加,脂质在肝脏组织中沉积增加。     

血脂康胶囊对高脂喂养大鼠内脏脂肪及代谢指标的影响

目的探讨血脂康胶囊对高脂喂养大鼠内脏脂肪及代谢指标的影响。方法选择6周龄健康雄性Wistar大鼠36只,随机分为对照组(n=12)组和高脂组(n=24),分别饲以基础饲料和高脂饲料,高脂组大鼠再随机分成两组:高脂模型组(n=12)和血脂康组(n=12),分别给予等剂量0.5%纤维素钠安慰剂和血脂康300 mg/(kg·d)灌胃,共观察12周后,检测各组大鼠附睾、肾周脂肪等内脏脂肪重量,计算体脂比,同时检测各组大鼠空腹血糖、胰岛素、总胆固醇、三酰甘油,计算胰岛素抵抗指数(HOMA-IR)。结果高脂喂养组大鼠12周后的体重和附睾、肾周脂肪重量及体脂比均显著高于正常对照组(P0.01),血脂康组虽较正常对照组大鼠也有增加(P0.05),但仍显著低于高脂喂养组大鼠(P0.01);高脂喂养组大鼠空腹血糖、空腹胰岛素、总胆固醇、三酰甘油及HOMA IR均显著高于正常对照组大鼠(P0.01)。血脂康组空腹血糖高于正常对照组(P0.01),空腹胰岛素和HOMA IR与正常对照组比较差异无统计学意义,而较高脂喂养组显著降低(P0.05);总胆固醇、三酰甘油虽较正常对照组有明显增加(P0.05或P0.01),但也显著低于高脂喂养组(P0.05或P0.01)。结论血脂康胶囊干预可以有效减少高脂喂养大鼠内脏脂肪聚集,从而显著改善糖脂代谢异常和胰岛素抵抗。     

饮食和运动干预对肥胖大鼠左心室收缩功能的影响

目的 研究饮食和运动干预对肥胖大鼠左心室收缩功能的影响。方法 3月龄SD大鼠高脂饲料喂养12周建立肥胖大鼠模型,随机分为恢复普通饮食不运动（HFD/NF-S）组、恢复普通饮食运动（HFD/NF-Ex）组、继续高脂饮食不运动（HFD-S）组和继续高脂饮食运动（HFD-Ex）组,跑步训练8周后,记录大鼠一般资料,检测大鼠血脂、血糖。超声心动图测量左心结构和功能,二维斑点追踪技术分析左心室应变和应变率。通过常规和特殊染色,观察大鼠心肌胶原纤维沉积、肥大细胞浸润程度、心肌自噬程度等。电镜下观察大鼠心肌超微结构改变。结果 HFD-S组大鼠相比HFD/NF-Ex组血糖、血脂明显升高（P<0.01）,心肌纤维化程度、肥大细胞浸润程度和心肌自噬程度明显增加（P<0.01）,室间隔及室壁增厚（P<0.05）,各节段应变和应变率减低（P<0.05）。HFD/NF-Ex组相比其他3组各项检查结果均有改善（P<0.05）,HFD/NF-S组和HFD-Ex组相比HFD-S组也有改善（P<0.05）但效果不如HFD/NF-Ex组。结论 饮食联合运动干预可延缓高脂诱导的肥胖大鼠的心肌重构、心肌纤维化及心肌自噬,纠正心功能。单一运动或饮食干预也可使肥胖大鼠心肌重构、纤维化和自噬程度减轻,改善心功能,但效果不如联合干预组。     

甘正复方对大鼠非酒精性脂肪肝模型细胞色素氧化酶P450 2E1、脂联素和肿瘤坏死因子α表达的影响

[目的]探讨细胞色素氧化酶P450 2E1(CYP2E1)、脂联素和肿瘤坏死因子α(TNF-α)在非酒精性脂肪性肝病(NAFLD)发病机制中的作用并观察甘正复方的疗效及作用途径。[方法]30只SD大鼠随机分为3组:正常组10只喂普通饲料;模型组10只和治疗组10只喂高脂饲料。治疗组高脂饮食12周后同时给予复方甘正10 ml/kg鼠重灌胃,至实验16周末处死所有大鼠,检测血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)活性,采用放射免疫法测定血清TNF-α和脂联素水平。肝组织标本石蜡切片,行苏木精-伊红染色,光镜下评估肝组织脂肪变性程度及炎症活动度。免疫组化和RT-PCR法检测肝组织CYP2E1蛋白和mRNA的表达。[结果]与正常组比较,模型组血清ALT、AST增加,治疗组较模型组血清ALT、AST下降(均P0.01);模型组血清TNF-α(3.40±0.18)μg/L,较正常组的(1.35±0.09)μg/L明显增高(P0.01),治疗组为(1.57±0.11)μg/L,显著低于模型组(P0.01)。模型组血清脂联素为(6.21±0.39)mg/L,较正常组的(12.14±0.83)mg/L明显降低(P0.01),治疗组为(9.33±0.45)mg/L,明显高于模型组(P0.01)。免疫组化法染色结果及PT-PCR法示模型组CYP2E1阳性表达增高,治疗组较模型组明显减少(P0.01),与正常组比较差异无统计学意义。[结论]甘正复方通过调控CYP2E1、脂联素和TNF-α的表达,参与NAFLD发病机制的多种途径,从而有效治疗大鼠NAFLD。     

The anorexigenic effects of metformin involve increases in hypothalamic leptin receptor expression

Metformin demonstrates anorectic effects in vivo and inhibits neuropeptide Y expression in cultured hypothalamic neurons. Here we investigated the mechanisms implicated in the modulation of feeding by metformin in animals rendered obese by long-term high-fat diet (diet-induced obesity [DIO]) and in animals resistant to obesity (diet resistant [DR]). Male Long-Evans rats were kept on normal chow feeding (controls) or on high-fat diet (DIO, DR) for 6 months. Afterward, rats were treated 14 days with metformin (75 mg/kg) or isotonic sodium chloride solution and killed. Energy efficiency, metabolic parameters, and gene expression were analyzed at the end of the high-fat diet period and after 14 days of metformin treatment. At the end of the high-fat diet period, despite higher leptin levels, DIO rats had higher levels of hypothalamic neuropeptide Y expression than DR or control rats, suggesting a central leptin resistance. In DIO but also in DR rats, metformin treatment induced significant reductions of food intake accompanied by decreases in body weight. Interestingly, the weight loss achieved by metformin was correlated with pretreatment plasma leptin levels. This effect was paralleled by a stimulation of the expression of the leptin receptor gene (ObRb) in the arcuate nucleus. These data identify the hypothalamic ObRb as a gene modulated after metformin treatment and suggest that the anorectic effects of the drug are potentially mediated via an increase in the central sensitivity to leptin. Thus, they provide a rationale for novel therapeutic approaches associating leptin and metformin in the treatment of obesity.     

二甲双胍对胰岛素抵抗大鼠脂肪肝的影响

目的探讨二甲双胍对胰岛素抵抗大鼠脂肪肝的影响。方法雄性wistar大鼠31只，随机分为正常组（n=8）和实验组（n=23）。正常组普通饮食，实验组高脂饮食，8周末从实验组中随机抽取7只证实造模成功。实验组再分为二甲双胍组（n=8）和模型对照组（n=8），6周后，胰岛素敏感性用正常血糖高胰岛素钳夹技术稳态时的葡萄糖输注率来评价；氨基转移酶、甘油三酯（TG）、游离脂肪酸（FFA）等以生物化学方法测定；胰岛素和肿瘤坏死因子α（TNFα）分别用放射免疫法和酶联免疫吸附法测定；肝细胞脂肪变性和肝脏的炎症程度在光学显微镜下评估。结果与模型对照组相比，二甲双胍组大鼠胰岛素抵抗明显改善，肝指数、附睾脂肪比重、体重明显下降，氨基转移酶、TG、FFA、TNFα明显降低，肝细胞脂肪变性和肝脏炎症情况有不同程度的改善。结论二甲双胍能够明显改善高脂饲养诱发脂肪肝大鼠的胰岛素抵抗和肝脏组织学，它可能成为治疗脂肪肝的新药物。     

熊去氧胆酸对节制饮食防治大鼠肥胖高脂血症性脂肪性肝炎的影响

目的 探讨熊去氧胆酸对节制饮食防治肥胖、高脂血症性脂肪性肝炎的影响。方法３５只ＳＤ大鼠持续１０周高脂饮食后，分为３组。模型组（ｎ＝１０）继续给子高脂饮食；低热卡饮食组（ｎ＝１０）恢复普通饮食，但仅给正常需要量的１／３，２周后处死；熊去氧胆酸组（ｎ＝１５）在 ＬＣＤ的同时经口给予熊去氧胆酸（２５０ｍｇ·ｋｇ－１·ｄ－１）。另设９只普通饮食饲养大鼠作正常对照。结果 与正常组相比，模型组大鼠体章、肝重明显增加、血脂和转氨酶升高，肝组织学检查示脂肪性肝炎；与模型组相比，低热年饮食组大鼠体重、肝重及肝组织脂肪变显著减轻，但血脂紊乱和肝组织炎症坏死改善并不明显；而熊去氧胆酸组血脂异常和ＡＳＴ以及肝组织炎症坏死程度均较低热卡饮食组减轻。结论 熊去氧胆酸有助于促进节食减肥大鼠血脂和脂肪性肝炎的康复。     

Effects of estrogen on cardiovascular injury in ovariectomized female DahlS.Z-Lepr(fa)/Lepr(fa) rats as a new animal model of metabolic syndrome

Although recent clinical trials have found an increased incidence of cardiovascular disease in women on estrogen replacement therapy, the underlying mechanism remains unclear. We have recently characterized DahlS.Z-Lepr(fa)/Lepr(fa) (DS/obese) rats, derived from a cross between Dahl salt-sensitive and Zucker rats, as a new animal model of metabolic syndrome. We have now examined the effects of estrogen replacement on cardiac pathophysiology in ovariectomized female DS/obese (Ovx-DS/obese) rats. Animals subjected to ovariectomy at 7 weeks of age were implanted subcutaneously with a 60-day release pellet containing 0.5 mg of 17β-estradiol (E(2)) or placebo at 8 weeks. Age-matched female homozygous lean littermates (DahlS.Z-Lepr(+)/Lepr(+) or DS/lean rats) of DS/obese rats served as controls. Animals were maintained on a normal diet and were subjected to echocardiography followed by various pathological analyses at 13 weeks of age. Ovx-DS/obese rats manifested hypertension at 7 weeks of age and thereafter and showed left ventricular (LV) fibrosis and diastolic dysfunction at 13 weeks. Treatment with E(2) attenuated hypertension in Ovx-DS/obese rats but had no effect on blood pressure in ovariectomized female DS/lean (Ovx-DS/lean) rats. E(2) treatment exacerbated LV fibrosis and diastolic dysfunction, as well as further increased cardiac oxidative stress and inflammation in Ovx-DS/obese rats, and it elicited similar effects in Ovx-DS/lean rats. E(2) reduced food intake, body weight, and visceral fat content in both Ovx-DS/obese and Ovx-DS/lean rats. E(2) treatment attenuated hypertension and obesity but exacerbated LV fibrosis and diastolic dysfunction in Ovx-DS/obese rats, with these latter effects being associated with increased cardiac oxidative stress and inflammation.     

白藜芦醇改善高脂诱导老龄小鼠肥厚性肥胖作用的研究

目的探讨白藜芦醇对老龄小鼠肥胖的影响及其可能的作用机制.方法分别将32周龄和48周龄小鼠随机分为3组:正常对照组进食普通饲料,每天灌胃1次0.3 ml生理盐水;高脂饮食处理组进食高脂饲料(含有21%脂肪和1.25%胆固醇),每天灌胃1次0.3 ml生理盐水;高脂饮食加白藜芦醇组进食高脂饲料,每天灌胃1次白藜芦醇(22.4 mg/kg,分散于0.3 ml生理盐水中).12周后称量各组小鼠体重,并进行脂肪组织取材及称重;采用酶联免疫吸附试验检测小鼠血浆瘦素浓度;通过实时荧光定量聚合酶链式反应方法检测小鼠肥厚性肥胖相关指标.结果高脂饮食加白藜芦醇组老龄小鼠体重及皮下脂肪含量分别为(34.43±3.23)g和(3.21±1.58)%,较高脂饮食组老龄小鼠(53.16±2.16)g和(4.86±0.64)%有明显下降(均P<0.01),并与普通饮食中年小鼠数据接近;与中年小鼠比较,白藜芦醇对高脂饮食老龄小鼠瘦素的抑制作用更为显著,高脂饮食加白藜芦醇组老龄小鼠血浆瘦素浓度(0.015±0.009)g/L,较高脂饮食组老龄小鼠(0.100±0.027)g/L明显下降,且低于普通饮食的老龄小鼠(F=19.85,P=0.001),与普通饮食中年小鼠相接近;白藜芦醇可以显著增加高脂饮食老龄小鼠皮下脂肪组织过氧化物酶体增殖物激活受体γ(PPARγ)和葡萄糖转运蛋白4(GLUT4)的表达,并降低肿瘤坏死因子-α(TNF-α)的表达(F=10.79、9.31、7.02,P=0.003、0.006,0.010).结论白藜芦醇可以显著改善老龄小鼠肥厚性肥胖,抑制瘦素分泌和上调PPARγ表达可能是其作用的关键机制.     

间歇有氧运动训练改善肥胖小鼠缺血后心脏功能恢复

目的 探讨有氧间歇运动训练（AIT）对高脂饮食诱导的肥胖小鼠心肌缺血再灌注（MI/R）损伤的影响和相关机制。 方法 30只2月龄C57小鼠随机分为:正常对照组;高脂饮食组;高脂饮食间歇训练组。喂养12周后,建立急性MI/R模型（缺血30 min,再灌注4 h）。于再灌注结束后不同时间点采用超声心动仪检测心脏功能,Western blot法检测心脏相关信号表达。 结果 与正常对照组相比,12周高脂饮食喂养导致小鼠肥胖,体质量显著增加（P<0.05）;AIT可有效降低高脂饮食肥胖小鼠的体质量,增加心脏质量/胫骨长度比率（P<0.05）;与正常对照组相比,高脂饮食肥胖小鼠MI/R损伤显著加重（P<0.05）;AIT可有效减轻肥胖小鼠心肌损伤,减小心肌梗死面积和血清LDH水平（均P<0.05）;AIT还显著改善MI/R后心肌功能恢复,有效提高左室射血分数（EF）和左室短轴缩短率（FS）（均P<0.05）。与高脂饮食组相比,AIT可显著增强高脂饮食肥胖小鼠心肌线粒体SIRT3和MnSOD表达,减少高脂饮食组MI/R心肌组织氧化应激（均P<0.05）。 结论 AIT可有效提高高脂饮食肥胖小鼠心肌线粒体SIRT3和MnSOD表达,增加线粒体抗氧化酶活性,进而减轻肥胖小鼠的MI/R损伤,促进缺血后心脏功能恢复。     

Obese-insulin resistance accelerates and aggravates cardiometabolic disorders and cardiac mitochondrial dysfunction in estrogen-deprived female rats

Women have a lower incidence of cardiovascular diseases (CVD) than men at a similar age but have an increased incidence of CVD and metabolic syndrome after menopause, indicating the possible protective effects of estrogen on cardiometabolic function. Although obesity is known to increase CVD risks, its impact on the heart on estrogen deprivation is still inconclusive. We investigated the effects of obese-insulin resistance on cardiometabolic function in estrogen-deprived ovariectomized rats. Adult female ovariectomized (O) or sham (S)-operated rats randomly received either normal diet (ND, 19.77 % fat) or high-fat diet (HF, 57.60 % fat) (n = 6/group) for 12 weeks. The heart rate variability (HRV), left ventricular (LV) performance, cardiac autonomic balance, cardiac mitochondrial function, metabolic parameters, oxidative stress, and apoptotic markers were determined at 4, 8, and 12 weeks. Insulin resistance developed at week 8 in NDO, HFS, and HFO rats as indicated by increased plasma insulin and HOMA index. However, only HFO rats had elevated plasma cholesterol level at week 8, whereas HFS rats had showed elevation at week 12. In addition, only HFO rats had depressed HRV, impaired LV performance indicated by decreased fractional shortening (%FS) and cardiac mitochondrial dysfunction indicated by increased mitochondrial ROS level, mitochondrial depolarization and swelling, as early as week 8, whereas other groups exhibited them at week 12. Either estrogen deprivation or obesity alone may impair metabolic parameters, cardiac autonomic balance, and LV and mitochondrial function. However, an obese insulin-resistant condition further accelerated and aggravated the development of these cardiometabolic impairments in estrogen-deprived rats.     

Anti-obesity effects of lipase inhibitor CT-II, an extract from edible herbs, Nomame Herba, on rats fed a high-fat diet

OBJECTIVE: To investigate the inhibitory effects of CT-II, extract of Nomame Herba, on lipase activity in vitro and on obesity in rats fed a high-fat diet in vivo. DESIGN: The assay for the inhibitory effect of CT-II on lipase activity was performed by measuring released free fatty acids after the incubation of the medium with CT-II, porcine pancreatic lipase and triolein (experiment 1). In vivo experiments, lean rats or obese rats (570-718 g) were fed a high-fat diet containing 60% fat with or without CT-II for 8 weeks (experiment 2), for 14 days (experiment 3) or for 12 weeks (experiment 4), respectively. MEASUREMENT: The time course of body weight, food intake, organ weight (parametrial fat, liver, heart and kidney) and plasma parameters (triglyceride, total cholesterol, glucose, AST, ALT and insulin), fecal output of total fat and total cholesterol were measured. Hepatic histological examinations were also performed. RESULTS: CT-II inhibited the porcine lipase activity dose-dependently in vitro (experiment 1). Body and liver weight were reduced and hepatic histological examination showed an amelioration of fatty liver in CT II treated animals (experiment 2). CT-II significantly inhibited body weight gain and plasma triglyceride elevation in a dose-dependent manner, without affecting food intake in lean rats fed the high-fat diet. Elevated plasma AST and ALT were also decreased (experiment 3). When obese rats fed the high-fat diet were treated with CT-II for up to 6 months, body weight was initially reduced and thereafter weight gain was significantly suppressed. Total body fat was also significantly reduced and significant reduction of plasma AST and ALT was observed (experiment 4). CONCLUSIONS: These results demonstrated that the lipase inhibitor CT-II is effective in preventing and ameliorating obesity, fatty liver and hypertriglyceridemia in rats fed a high-fat diet.