红花黄色素改善肥胖小鼠脂肪肝及胰岛素抵抗的研究

摘 要 目的：探讨红花黄色素对饮食诱导肥胖小鼠的体脂、脂肪肝及胰岛素抵抗的影响。 方法: 4周龄雄性C57BL/6小鼠喂以高脂饮食8周,建立肥胖模型,随后进行6周的腹腔注射红花黄色素（100 mg·kg^-1·d^-1）干预。实验终点行腹腔葡萄糖耐量试验（IPGTT）及胰岛素糖耐量（ITT）试验,小鼠处死后,检测体脂、血脂等代谢参数,并采集附睾脂肪及肝脏组织,行HE染色,定量脂肪细胞面积、观察肝脏脂肪变性程度。结果: 红花黄色素可显著降低肥胖小鼠的体质量、体脂含量、脂肪细胞面积、肝脏重量及血脂水平（P<0.05）,并且明显减轻肥胖小鼠肝脏脂肪变性程度,同时,IPGTT及ITT实验显示红花黄色素可显著改善肥胖小鼠的糖耐量异常,增强胰岛素的敏感性（P<0.05）。结论:红花黄色素可显著降低饮食诱导肥胖小鼠的体脂含量,减轻脂肪肝,改善糖耐量异常及胰岛素抵抗。     

罗格列酮对糖耐量受损大鼠血清脂联素和肝脏脂联素受体表达的影响

目的探讨罗格列酮对糖耐量受损大鼠血清脂联素和肝脏脂联素受体-1表达的影响。方法60只Wistar雄性大鼠随机分为对照组(普通饲料喂养)和高脂组(高脂饲料喂养)。每周记录体质量变化,每2周作1次糖耐量试验;用HOMA胰岛素抵抗指数评价胰岛素抵抗程度,用反转录聚合酶链反应和蛋白印迹法分别测定脂联素受体1 mRNA和蛋白在肝脏的表达,成模后用罗格列酮干预4周。结果①12周时高脂组有18只大鼠成模,其2 h血糖均值达到了糖耐量受损的诊断标准,空腹血糖高于对照组(P<0.05),但未达到空腹血糖受损的诊断标准;②成模组大鼠体质量明显增加,空腹胰岛素和HOMA-IR指数高于对照组(P<0.05);③罗格列酮干预4周后血清脂联素水平较模型组升高(P<0.05),肝脏组织脂联素受体1 mRNA和蛋白的表达与模型组相比差异无统计学意义(P>0.05)。结论脂联素表达的下降在高脂饮食导致的胰岛素抵抗的发生中起着重要作用,罗格列酮可升高血清脂联素水平,但不影响肝脏脂联素受体-1的表达。     

双去甲氧基姜黄素对肥胖模型小鼠糖脂代谢的影响及机制

目的 研究双去甲氧基姜黄素(bisdemethoxycurcumin,BDMC)对高糖高脂饮食诱导的肥胖小鼠胰岛素抵抗、糖脂代谢紊乱的影响,并探讨其机制。方法 C57BL/6小鼠40只随机分为正常组(10只)和高糖高脂饮食组(30只),正常组小鼠给予常规饲料,其余小鼠饲喂高糖高脂饮食诱导肥胖,造模8周。造模成功后,高糖高脂饮食组小鼠随机分为模型组、BDMC低剂量组(20 mg·kg^-1)、BDMC高剂量组(40 mg·kg^-1),每组10只。分别按剂量灌胃给药,每日1次,每周5次,连续8周。给药结束后,检测小鼠体质量、肝脏及脂肪重量,观察肝脏病理改变及脂质堆积情况,监测小鼠血糖、血脂、血清胰岛素等生化指标,并考察BDMC对TRPV1、AMPK及下游胰岛素信号、糖脂代谢通路的影响。结果 与正常组相比,模型组小鼠体质量及脏器指数增加,肝脏出现明显的病理改变,脂质堆积严重,血清胰岛素、血糖、血脂参数(TC、TG、LDL-C)显著增高,HDL-C显著降低;肝损伤(ALT、AST)加重;肝脏组织中TRPV1、SREBP、FAS蛋白表达显著升高,p-IRS1、p-AMPK、GLUT4、p-ACC表达显著降低。与模型组相比,给予BDMC治疗后,肝脏脂质堆积减少,组织病理改变得到改善,血糖、血清胰岛素、TC、TG、LDL-C、ALT、AST显著降低(P<0.05),HDL-C显著升高,肝脏中p-IRS1、p-AMPK、GLUT4、p-ACC表达升高,TRPV1、SREBP、FAS表达显著降低(P<0.05)。结论 BDMC能改善胰岛素抵抗,调节糖脂代谢紊乱,治疗高糖高脂饮食诱导的肥胖,其作用可能与调节TRPV1和AMPK信号通路有关。     

TNF-α在饮食诱导糖尿病大鼠肝脏的表达及罗格列酮的干预研究

目的 探讨肿瘤坏死因子-α(TNF-α)在高糖、高脂饮食诱导的2型糖尿病大鼠肝脏的表达以及罗格列酮对2型糖尿病合并脂肪肝的治疗作用.方法 通过高糖、高脂饮食结合小剂量链脲佐菌素的方法建立2型糖尿病大鼠合并脂肪肝的动物模型,再给予罗格列酮进行干预治疗.4周、8周末测量大鼠血糖、血脂和胰岛素水平,18周末测各组大鼠血糖、血清血脂、胰岛素、丙氨碱转氨酶、TNF-α和瘦素水平,并检测TNF-α在肝脏的蛋白表达水平.结果 TNF-α在糖尿病组大鼠肝脏的表达明显增加,罗格列酮可以显著降低糖尿病大鼠血糖、血脂和肝脏的脂肪含量,改善胰岛素抵抗状态,降低TNF-α在肝脏的表达水平.结论 罗格列酮对合并脂肪肝的糖尿病大鼠具有一定的治疗作用.     

西格列汀对肥胖大鼠代谢指标及脂肪因子chemerin脂联素水平的影响

目的 研究西格列汀对肥胖大鼠代谢指标及脂肪因子chemerin、脂联素(ADPN)水平的影响及其可能机制,并探讨chemerin及ADPN与肥胖的关系。方法 将30只大鼠随机分为正常对照组(NC组)、肥胖对照组(HF组)和肥胖西格列汀干预组(SP组),ELISA法分别测定干预前后各组大鼠生化指标,Western blot 法检测大鼠脂肪、肝脏、肌肉及肾脏组织chemerin及ADPN蛋白表达水平。结果 与NC组相比,HF组大鼠血清chemerin、体质量(BW),空腹血糖(FBG)、胰岛素(FINS)、总胆固醇(TG)、甘油三酯(TC)、低密度脂蛋白胆固醇(LDL-C),胰岛素抵抗指数(HOMO-IR)增高,血清ADPN及高密度脂蛋白胆固醇(HDL-C)降低(P<0.05),HF组大鼠脂肪、肝脏、肌肉及肾脏组织的chemerin蛋白表达量较NC组对应组织的表达量增加(P<0.05),脂肪、肝脏及肌肉组织的ADPN表达量减少(P<0.05)。与HF组相比,SP组大鼠FBG、FINS、TC、TG、LDL-C、HOMO-IR、血清chemerin水平降低, HDL-C及血清ADPN水平升高(P<0.05),脂肪、肝脏、肾脏及肌肉组织的chemerin蛋白表达量减少,脂肪、肌肉组织的ADPN表达增加(P<0.05)。干预前chemerin、ADPN与BW、FBG、TG、HDL-C、LDL-C、FINS、HOMO-IR有相关性,干预后chemerin、ADPN与BW、LDL-C、FINS、HOMO-IR有相关性,ADPN与HDL-C呈正相关。结论 chemerin及ADPN参与糖脂代谢过程,西格列汀可改善血清学各代谢指标,并通过影响chemerin及ADPN来改善肥胖大鼠胰岛素敏感性。     

罗格列酮对胰岛素抵抗大鼠骨骼肌蛋白激酶B表达的影响

目的 :探讨胰岛素增敏剂罗格列酮对胰岛素抵抗大鼠骨骼肌蛋白激酶B(PKB)表达的影响。方法 :应用高脂饲料喂养复制胰岛素抵抗大鼠模型。应用Westernblotting方法检测骨骼肌中PKB的表达。结果 :持续高脂饲料喂养组大鼠产生了明显胰岛素抵抗 ,骨骼肌PKB的表达较正常对照组显著降低 (OD值 8.2 4±s 0 .11vs 9.36± 0 .18,P <0 .0 1) ,罗格列酮治疗组和正常饲料替代组大鼠胰岛素抵抗明显改善 ,PKB的表达较持续高脂饲料喂养组大鼠明显增加 (OD值分别为 8.89± 0 .0 8,8.4 0± 0 .0 9vs 8.2 4± 0 .11,P <0 .0 1)。结论 :高脂喂养的大鼠胰岛素抵抗的产生与骨骼肌胰岛素刺激的PKB表达降低有明显关系 ,罗格列酮能显著增加已经降低了的胰岛素抵抗大鼠骨骼肌中PKB的表达 ,部分恢复受损的胰岛素信号转导 ,进而明显改善胰岛素抵抗 ,这可能也是罗格列酮减轻胰岛素抵抗的作用机制之一。     

芝麻素对肾性高压伴高脂高糖饮食大鼠的抗脂毒作用

观察芝麻素对肾性高压伴高脂高糖饮食大鼠的抗脂毒作用。两肾一夹术和高脂高糖饮食13周诱导复合模型大鼠34只, 于第5周开始连续灌胃给予芝麻素 (120、60及30 mg·kg⁻¹·d⁻¹) 8周。测定血压、血脂、血糖、游离脂肪酸、胰岛素、TNF-α和IL-6水平; 半定量分析胰腺、肾周脂肪、肝脏病理学改变。结果发现, 芝麻素 (120及60 mg·kg⁻¹·d⁻¹) 能降低模型大鼠血压、血脂、血糖、TNF-α、IL-6和FFA水平; 改善胰岛素抵抗和糖耐量异常; 减轻体重、内脏脂肪、胰腺和肝脏湿重及其脏器指数; 减少胰岛细胞增生和脂肪及肝脏细胞中脂滴空泡的数目。提示芝麻素具有抗脂毒作用, 其机制可能与肝细胞脂质沉积减轻、脂肪依赖炎症因子TNF-α和IL-6的释放减少以及减轻胰岛素抵抗有关。     

罗格列酮对IR大鼠血清visfatin、VCAM-1水平及内脏脂肪组织visfatin mRNA表达的影响

目的研究罗格列酮对胰岛素抵抗（IR）大鼠血清内脏脂肪素（visfatin）与血管细胞间黏附分子-1（VCAM-1）的水平,内脏脂肪组织visfatinmRNA表达的影响。方法雄性Wistar大鼠50只作为研究对象,高脂饮食4周,诱导IR模型成功后,给予罗格列酮组药物干预,继续喂养8周。ELISA测定空腹血清visfatin和VCAM-1,RT-PCR方法测定内脏脂肪visfatinmRNA表达。结果 （1）高脂喂养12周大鼠血清visfatin、VCAM-1升高（P〈0.01,P〈0.05）。（2）罗格列酮组血清VCAM-1下降（P〈0.01）;visfatin无明显变化（P〉0.05）。（3）高脂喂养大鼠与正常对照组比较,内脏脂肪组织visfatinmRNA表达增强（P〈0.05）,罗格列酮组与高脂对照组比较,visfatinmRNA表达差异无统计学意义（P〉0.05）。（4）相关分析显示血清visfatin与VCAM-1、TG、TC、内脏脂肪含量呈正相关（r值分别为0.910、0.499、0.367、0.446,P〈0.05）;多元逐步回归分析显示visfatin是VCAM-1的独立相关因素。结论罗格列酮可降低VCAm-1水平,可显著增强胰岛素敏感性,并改善血管内皮功能。     

罗格列酮对2型糖尿病大鼠肝脏线粒体功能障碍的影响

目的探讨罗格列酮对2型糖尿病大鼠肝脏线粒体功能障碍的影响,为阐明糖尿病的发病机制以及罗格列酮治疗糖尿病的药理作用提供新的实验依据。方法采用高脂饲养加腹腔注射小剂量链脲佐菌素(35 mg.kg-1)诱导2型糖尿病大鼠;检测肝脏线粒体琥珀酸脱氢酶及细胞色素C氧化酶活性、线粒体膜电位、肝ATP含量等指标以评价线粒体功能;测定过氧化物酶体增殖物激活受体γ辅激活因子1α(PGC-1α)的mRNA水平及线粒体基因细胞色素C氧化酶亚基Ⅰ(COXⅠ)与核基因-βactin的拷贝数之比来反映线粒体的生物合成;并检测解偶联蛋白2(UCP2)的基因转录、NO含量及NOS活性、脂质过氧化产物MDA含量和抗氧化酶SOD活性等指标以探讨糖尿病大鼠肝脏线粒体功能障碍的可能机制。结果糖尿病大鼠血糖、血胰岛素水平显著升高,胰岛素敏感性指数明显降低,表明2型糖尿病大鼠模型建立成功。与正常大鼠相比,2型糖尿病大鼠肝脏线粒体琥珀酸脱氢酶及细胞色素C氧化酶活性下降、线粒体膜电位降低、ATP生成减少并伴有肝脏线粒体生物合成抑制,提示线粒体功能损害;此外,肝脏UCP2转录上调,同时伴肝MDA含量增加,SOD及NOS活性降低,NO含量减少。罗格列酮治疗8周后,不仅明显改善糖尿病大鼠肝脏线粒体功能的损害,而且增加肝脏线粒体生物合成。进一步研究揭示罗格列酮对糖尿病大鼠肝脏线粒体功能的保护作用可能与下调UCP2 mRNA水平,上调PGC-1α转录表达,降低体内氧化应激水平有关。结论罗格列酮对糖尿病大鼠肝脏线粒体功能障碍具有保护作用。     

滇结香花对他克莫司诱导的糖尿病大鼠胰腺的保护作用及机制研究

目的 研究滇结香花乙酸乙酯提取物（ethyl acetate extraction from Edgeworthia gardneri Flos,EG）对他克莫司诱导的糖尿病模型大鼠胰腺的保护作用及其机制。方法 将40只SD大鼠随机分为正常组、模型组、滇结香花组和罗格列酮组,每组10只。采用他克莫司单因素干预制作SD大鼠糖尿病模型,通过检测大鼠空腹血糖、胰岛素、糖化血红蛋白水平,显微镜下观察胰腺组织病理学变化,评价EG降糖和保护胰腺组织的作用。并采用RT-PCR和Western blot分别检测胰腺组织中胰岛素受体底物蛋白2（insulin receptor substrate 2,IRS-2）mRNA和蛋白表达水平,探究EG保护糖尿病胰腺组织的作用机制。结果 与正常组比较,他克莫司诱导的糖尿病模型大鼠血糖、胰岛素抵抗指数、糖化血红蛋白升高,胰岛素、胰岛素分泌指数降低（P<0.05）。与模型组比较,滇结香花组血糖、糖化血红蛋白降低,胰岛素、胰岛素分泌指数升高（P<0.05）,大鼠胰腺组织IRS-2 mRNA表达量和IRS-2蛋白表达量增加（P<0.05）。HE染色观察到滇结香花组大鼠胰腺组织切片中胰岛细胞形态结构明显改善,细胞数目增多,排列较整齐,胞浆分布均匀。结论 EG能降低他克莫司诱导的糖尿病模型大鼠的血糖、糖化血红蛋白水平,其机制可能是通过胰腺胰岛素信号转导通路中胰岛素受体底物,保护胰腺,促进胰岛素分泌,增强糖代谢。     

罗格列酮对阻塞性睡眠呼吸暂停综合征模型血清和脂肪组织抵抗素、瘦素表达的影响

目的探讨罗格列酮对阻塞性睡眠呼吸暂停综合征(OSAS)陆川猪模型血清和脂肪组织抵抗素、瘦素mRNA及蛋白表达量的影响。方法选取23只陆川猪,随机分为:正常对照组(6只)、模型组(6只)、罗格列酮干预组(6只)。罗格列酮干预组喂服罗格列酮0.2 mg.kg-1.d-1;正常对照组及OSAS模型组给予等量生理盐水,每天1次。12周后处死各组实验动物并取材。采用多导睡眠呼吸监测仪进行监测,免疫放射分析法检测3组血清抵抗素、瘦素水平的变化,分别用RT-PCR法、Western blot法检测大网膜脂肪组织抵抗素、瘦素基因及蛋白的表达。结果与对照组比较,OS-AS猪模型血清抵抗素、瘦素水平升高,脂肪组织抵抗素、瘦素mRNA及蛋白表达灰度值升高,差异有统计学意义(P<0.01);与模型组比较,罗格列酮干预治疗后,呼吸暂停低通气指数(AHI)降低,最低血氧饱和度(MinSaO2)升高(P<0.05);血清抵抗素、瘦素水平下降、脂肪组织抵抗素mRNA、瘦素mRNA及蛋白表达灰度值降低(P<0.05),但仍高于对照组水平(P<0.05)。结论罗格列酮可能通过减轻胰岛素抵抗,下调血清和脂肪组织抵抗素、瘦素mRNA及蛋白表达,从而发挥其对OSAS的干预作用。     

Insulin therapy stimulates lipid synthesis and improves endocrine functions of adipocytes in dietary obese C57BL/6 mice

Aim:

To evaluate whether insulin intervention could affect the metabolic and endocrine functions of adipose tissue.

Methods:

C57BL/6 mice were fed on a high-fat-diet for 12−16 weeks to induce insulin resistance. Insulin intervention was administered in the high-fat-diet mice for 4 weeks at 12 weeks (early insulin treatment) or 16 weeks (late insulin treatment). Intraperitoneal glucose tolerance tests were performed before and after insulin treatment. Expression levels of factors involved in the triglyceride synthesis and endocrine functions of adipose tissue including phosphoenolpyruvate carboxykinase (PEPCK-C), fatty acid synthase (FAS), aquaporin 7 (AQP7), adiponectin, visfatin, and interleukin-6 (IL-6) were determined by Western blot.

Results:

In the obese mice, glucose tolerance was impaired; triglyceride content was increased in the liver tissue; protein expression of FAS and adiponectin was decreased; expression of visfatin was increased in adipose tissue. After 4-week insulin treatment, glucose tolerance was improved; triglyceride content was decreased in the liver and skeletal muscle; expression of PEPCK-C, FAS, and adiponectin was increased in the adipose tissue; IL-6 and AQP7 expression was reduced in the fat. Early insulin treatment had better effect in increasing the expression of FAS and PEPCK-C and decreasing the expression of IL-6.

Conclusion:

These results indicate that insulin can target adipocytes for improvement of insulin sensitivity through stimulating triglyceride synthesis and partly improving endocrine functions.     

牛磺酸对胰岛素抵抗大鼠脂肪组织PAI-1mRNA表达的影响

目的 :观察牛磺酸对胰岛素抵抗大鼠的治疗作用。方法 :选择 SD雄性大鼠 ,按体重随机分为正常组和造模组 ,造模组大鼠饲以特殊高脂饲料 30 d,造成胰岛素抵抗动物模型 ;经牛磺酸治疗 30 d后 ,取血检测血糖、胰岛素等指标 ,计算胰岛素抵抗敏感指数。运用 RT- PCR技术测定大网膜脂肪组织 PAI- 1m RNA的表达。结果 :采用特殊高脂饲料可以成功诱导胰岛素抵抗动物模型 ;牛磺酸可提高胰岛素抵抗大鼠胰岛素敏感指数 (P<0 .0 5 ) ,下调脂肪组织PAI- 1m RNA的表达。结论 :牛磺酸具有提高胰岛素敏感性作用 ,以及阻断 PAI- 1m RNA的过度表达的综合效应。     

Insulin secretion and carbohydrate metabolism in the dystrophic mouse.

Dystrophic mice were investigated with regard to their regulation of blood glucose and insulin secretion in vivo. The following were also measured: tissue glycogen levels, activity of the glycogenolytic hydrolase, acid amyloglucosidase, and in vitro glucose utilization by liver, muscle and adipose tissue. Basal levels of blood glucose and plasma insulin of dystrophic mice were essentially within the same range as in the clinically unaffected littermate controls. Dystrophic mice had a decreased tolerance to glucose and glibenclamide; the secretion of insulin in response to these secretagogues was moderately reduced. Insulin release following beta-adrenergic stimulation, however, was increased in the dystrophic mice. Glycogen levels and acid amyloglucosidase activity were increased in dystrophic muscles but were normal in liver. Acid amyloglucosidase activity in pancreatic islets was lower in the dystrophic mouse. Glucose utilization in vitro appeared normal in liver tissue from dystrophic mice; in dystrophic muscle there was a threefold increase in 14CO2-production with no concomitant increase in either glycogen or 14C-incorporation into glycogen. 14CO2 production and 14C-incorporation into lipid and glycogen were increased in dystrophic adipose tissue. We suggest that the decreased glucose tolerance, and the reduced insulin response to glucose in the dystrophic mouse are compensated by an increased glucose utilization in muscle and adipose tissue and an increased beta-adrenergic-mediated secretion of insulin.     

Site-specific modulation of white adipose tissue lipid metabolism by oleoyl-estrone and/or rosiglitazone in overweight rats

In spite of their shared decrease of insulin resistance, oleoyl-estrone [OE], and rosiglitazone show diverging effects on body fat mass and distribution. In this study, we studied whether their effects on white adipose tissue [WAT] were due to a shared or synergistic mechanism of action. Combined effects of OE and rosiglitazone 10-day treatment on WAT lipid, cell mass/number, and the expression of key lipid metabolism and regulatory agents were studied using an adult male overweight rat model. OE decreased WAT cell mass and lipids, parameters not changed by rosiglitazone. The effects of OE and—specially—rosiglitazone were more marked in small-cell WAT (i.e., mesenteric and subcutaneous sites) than in larger cell WAT (retroperitoneal and perigonadal). OE decreased the expressions in WAT of lipogenic enzymes, lipoprotein lipase, PPARs, and SREBP1c, effects symmetrically reversed by rosiglitazone. OE showed no effects on hormone-sensitive lipase expression, which was increased by rosiglitazone. OE strongly inhibited WAT lipogenesis, leaving lipolysis unchanged, thus unbalancing (and helping mobilize) WAT lipid stores. Rosiglitazone acted practically only on small-cell WAT sites, where it favored lipogenesis, but also stimulated lipolysis, which resulted in limited changes in lipid stores. Combination of OE and rosiglitazone induced less fat loss than OE alone.     

罗格列酮的胰岛素增敏作用和胰岛素抵抗改善作用

目的　观察罗格列酮的胰岛素增敏作用和胰岛素抵抗改善作用。方法　大鼠尾静脉注射链佐菌素 (5 0mg·kg-1)制备IDDM模型 ,观察单用罗格列酮、单用小剂量胰岛素 (皮下注射 2 5U·鼠 -1)、罗格列酮并用小剂量胰岛素的降糖作用 ;大鼠尾静脉注射卡介苗 (10mg·鼠 -1)制备免疫性胰岛素抵抗模型 ,观察罗格列酮对模型的葡萄糖输注速率的回升作用。结果　罗格列酮 1,3 ,10 μmol·kg-13个剂量组连续灌胃给药 8d ,均未能降低正常大鼠血糖 ,也未能降低链佐菌素所致糖尿病大鼠血糖 ;但在并用小剂量胰岛素条件下 ,罗格列酮 3 ,10 μmol·kg-1连续灌胃给药 8d ,能降低链佐菌素所致糖尿病大鼠血糖 ;罗格列酮 10 μmol·kg-1连续灌胃给药 8d后 ,用正糖钳技术检测 ,免疫性胰岛素抵抗模型亚极高和极高胰岛素状态下的葡萄糖输注速率均得到回升。结论　罗格列酮具有胰岛素增敏作用和胰岛素抵抗改善作用     

荔枝核皂苷和荔枝核黄酮对HepG2细胞胰岛素抵抗作用研究

目的 探讨荔枝核皂苷、荔枝核黄酮对胰岛素抵抗HepG2细胞糖代谢的影响。 方法 采用高浓度胰岛素培养基诱导HepG2细胞形成胰岛素抵抗模型,葡萄糖氧化酶法测定对照组、荔枝核皂苷组、荔枝核黄酮组、罗格列酮组细胞培养上清液中的葡萄糖含量,观察荔枝核皂苷、荔枝核黄酮对HepG2细胞胰岛素抵抗的作用。 结果 HepG2细胞在10^-6mol/L的胰岛素中作用24 h,细胞对胰岛素的抵抗作用最为明显。以此条件构建胰岛素抵抗细胞模型,对该模型给予荔枝核皂苷、荔枝核黄酮干预后,细胞培养上清液中葡葡糖含量未能显著降低。 结论 本研究提示荔枝核皂苷、荔枝核黄酮不能有效改善胰岛素抵抗。     

Pueraria lobata root polysaccharide alleviates glucose and lipid metabolic dysfunction in diabetic db/db mice

ContextPueraria lobata (Willd.) Ohwi (Fabaceae) root extract can lower blood glucose levels; however, whether Pueraria lobata root polysaccharide (PLP) possesses these effects is still unknown.ObjectiveThis study evaluates the therapeutic effect of PLP on diabetic metabolic syndrome.Materials and methodsThe db/m mice were assigned to normal control group (NC), db/db mice were divided into four groups randomly (n = 8). The db/db mice received rosiglitazone (10 mg/kg BW) or PLP (100 or 200 mg/kg BW) via oral gavage for 6 weeks. Afterward, blood glucose, insulin, and glycogen content were assayed, and insulin tolerance test (ITT), oral glucose tolerance test (OGTT) were performed. Glucose and lipid metabolism-related parameters and gene expression levels were assayed by ELISA and RT-PCR, respectively.ResultsAfter treatment with HPLP, the values of body weight, epididymal fat, subcutaneous fat, fasting blood glucose, insulin, and HOMA-IR decreased to 45.89 ± 1.66 g, 1.65 ± 0.14 g, 1.97 ± 0.16 g, 14.84 ± 1.52 mM, 9.35 ± 0.98 mU/L, and 5.56 ± 1.26, respectively; the levels of TG, TC, LDL-C, and FFA decreased to 1.67 ± 0.11 mmol/L, 6.23 ± 0.76 mmol/L, 1.29 ± 0.07 mmol/L, and 1.71 ± 0.16 mmol/L, respectively. HPLP down-regulated PEPCK, G6PC, FOXO1, SREBP-1, and ACC mRNA expression (p < 0.01), and up-regulated GS, Akt2, PI3K, GLUT2, PPARα, and LDLR mRNA expression in the liver (p < 0.01).Discussion and conclusionPLP exerts antidiabetic effects via activating the PI3K/AKT signalling pathway, thus improving insulin resistance, glucose, and lipid metabolism in db/db mice. Thus, PLP may be considered as a potential antidiabetic agent in clinical therapy.     

来曲唑联合45%高脂饲料诱导生殖内分泌及代谢表型异常的多囊卵巢综合征大鼠模型研究

目的 建立来曲唑联合高脂饲料诱导SD雌性大鼠多囊卵巢综合征（PCOS）内分泌及代谢异常的动物模型。方法 选取18只21日龄雌性大鼠喂养45%高脂饲料16周,第6周龄开始服用来曲唑直至造模结束;8只对照组大鼠常规饲料喂养,第6周龄服用生理盐水。观察阴道涂片及卵巢组织学变化,比较每周体重变化,测定脏器重量、血清睾酮水平、糖耐量、血脂水平、空腹胰岛素以及胰岛素敏感指数。结果 与对照组比较,模型组大鼠体重增加,卵巢、腹股沟脂肪质量增加,子宫、垂体质量及脏器指数显著减少。模型组大鼠卵巢呈多囊样改变,颗粒细胞层减少,白膜增加。模型组大鼠的三酰甘油和低密度脂蛋白升高,糖耐量曲线下面积增加,血清睾酮水平上升,空腹胰岛素水平升高,胰岛素敏感性降低。结论 来曲唑联合高脂饲料可以建立有效的内分泌及代谢表型异常PCOS动物模型。