山药多糖对昆明种小鼠生长性能及肠道菌群的影响

目的分析山药多糖对昆明种小鼠的生长性能及盲结肠乳酸杆菌、双歧杆菌、肠杆菌及肠球菌的影响。方法选取48只健康昆明种小鼠,雌雄各半,分为空白对照组(灌胃生理盐水)、山药多糖高剂量组(400 mg/kg)、中剂量组(200 mg/kg)和低剂量组(100 mg/kg),每天对小鼠体重及采食量进行准时记录。采集第28天的小鼠盲结肠,检测肠道菌群变化。结果当灌胃高、中剂量山药多糖28 d时,小鼠体重与对照组相比有统计学意义(P<0.05);同时,在高剂量的小鼠盲结肠内,肠杆菌与肠球菌的菌群数量与对照之间存在显著差异(P<0.01),而双歧杆菌和乳酸杆菌的增殖与对照相比,在高剂量和中剂量组均有统计学意义(P<0.01或P<0.05)。结论长期灌胃山药多糖对小鼠的生长性能和肠道菌群有显著影响。     

壳寡糖及其衍生物对糖尿病大鼠糖耐量及肠道微生态平衡的影响

目的:研究不同剂量的壳寡糖和N-乙酰氨基单糖对STZ诱导的糖尿病大鼠的糖耐量作用及肠道微生态平衡的影响.方法:按65 mg/kg体质量一次性ip STZ制备糖尿病大鼠模型.大鼠随机分为9组:正常对照组,二甲双胍阳性对照组,阴性对照组,壳寡糖高、中、低剂量组,N-乙酰氨基单糖高、中、低剂量组.正常对照组、阴性对照组每天灌胃蒸馏水(10 mL/kg);二甲双胍阳性对照组每天200 mg/kg灌胃;壳寡糖、N-乙酰氨基单糖组分别按250,500,1500 mg/kg每天灌胃,连续60 d,然后观察各组大鼠的一般状况和饮食.按2.5 g/kg体质量葡萄糖水溶液灌胃(ig),测定各组大鼠0,0.5,1,2h耐糖血糖值,并分别对各组大鼠肠道菌群进行培养,计数并计算B/E值.结果:不同剂量的壳寡糖和N-乙酰氨基单糖均能不同程度改善糖尿病大鼠的体质量减轻、多饮、多食等症状,中、高剂量组的效果要优于低剂量组.各模型组的葡萄糖糖耐量均有不同程度受损.壳寡糖各组葡萄糖耐量的显著改善(P<0.01),中剂量组效果最好;N-乙酰氨基单糖低剂量和中剂量显著改善葡萄糖耐量(P<0.05),低剂量组的效果最好.糖尿病大鼠肠道内大肠肝茵和肠球菌数量升高,而乳酸杆菌和双歧杆菌的数量明显下降.壳寡糖各剂量组可明显降低大肠肝茵和肠球菌的数量(P<0.01),对双歧杆菌和乳酸杆菌的增殖作用也有显著作用(P<0.01),且改善效果随着剂量的增加而增加;N-乙酰氨基单糖各剂量组随着剂量的增加使大肠杆菌和肠球菌的数量降低,高剂量组乳酸杆菌的增殖作用显著提高(P<0.01).单纯糖尿病大鼠组需氧菌总数量升高,而厌氧菌总数量升高明显下降,厌氧菌与需氧茵之比及B/E值<1.壳寡糖各剂量组均可使B/E值显著升高(P<0.01);N-乙酰氨基单糖高剂量组厌氧茵总数显著改善(P<0.05).结论:不同剂量的壳寡糖和N-乙酰氨基单糖均能不同程度的改善糖尿病大鼠的体质量减轻、多饮、多食等症状,改善葡萄糖耐量,对肠道微生态有调节作用.     

麦冬皂苷介导AMPK/Akt/mTOR通路对糖尿病大鼠心肌细胞自噬的影响

目的探究麦冬皂苷对2型糖尿病大鼠心肌细胞自噬以及AMPK/Akt/mTOR通路的影响。方法8周龄雄性C57BL/6J大鼠58只,随机分为对照组(n=8)和糖尿病模型组(n=50)。对照组给予基础饮食,糖尿病模型组经高脂饮食联合腹腔注射链脲佐菌素(STZ)建立2型糖尿病模型,随机分为模型组、罗格列酮组和麦冬皂苷低、中、高剂量组,各10只。罗格列酮组灌胃给予2 mg/kg罗格列酮,麦冬皂苷低、中、高剂量组分别灌胃给予50、100、200 mg/kg麦冬皂苷,其余两组灌胃给予等量生理盐水,1/d,连续给药6周。测定大鼠外周血血清学指标、血压、心率等;超声心动图检测心功能E峰、A峰流速比值(E/A)、E波减速时间(EDT)、左室等容舒张时间(IVRT);苏木精-伊红(HE)染色观察心脏组织病理变化;蛋白质印迹技术(Western blot)测定自噬相关蛋白Beclin1、LC3与腺苷酸活化蛋白激酶(AMPK)、Akt、哺乳动物雷帕霉素靶蛋白(mTOR)及其磷酸化水平变化。结果 (1)模型组大鼠空腹血糖、空腹胰岛素、心率、三酰甘油、总胆固醇、心脏重量显著高于对照组(P0.05);麦冬皂苷或罗格列酮干预后大鼠空腹血糖、空腹胰岛素、心率、三酰甘油、总胆固醇、心脏重量显著低于模型组(P0.05),且麦冬皂苷组具有剂量依赖关系。(2)与对照组比较,模型组心脏E/A比值显著降低、EDT和IVRT显著延长(P0.05);与模型组比较,麦冬皂苷各剂量组和罗格列酮组心脏E/A比值显著升高、EDT和IVRT显著缩短(P0.05)。(3)模型组心脏组织Beclin1/GAPDH、LC3-Ⅱ/LC3-Ⅰ比值显著低于对照组(P0.05);麦冬皂苷各剂量组和罗格列酮组心脏组织Beclin1/GAPDH、LC3-Ⅱ/LC3-Ⅰ比值显著高于模型组(P0.05)。(4)与对照组比较,模型组心脏组织p-AMPK/AMPK比值显著升高、p-Akt/Akt与p-mTOR/mTOR比值显著降低(P0.05);与模型组比较,麦冬皂苷各剂量组和罗格列酮组心脏组织p-AMPK/AMPK比值显著降低(P0.05)、p-Akt/Akt和p-mTOR/mTOR比值显著升高(P0.05)。结论麦冬皂苷能促进2型糖尿病大鼠心肌细胞自噬,改善大鼠心脏功能,其机制可能与AMPK活化、Akt/mTOR通路抑制有关。     

甘露低聚糖对小鼠肠道菌群的调节作用

[目的]研究甘露低聚糖(MOS)对小鼠肠道菌群的调节作用.[方法]40只小鼠随机分为空白对照组及MOS大、中、小剂量组.于不同剂量的MOS灌胃10 d前后分别采集小鼠粪便,检查肠道内双歧杆菌、乳杆菌、肠杆菌及肠球菌.[结果]MOS中、大剂量组灌胃MOS 10 d前后比较,小鼠肠道内双歧杆菌、乳杆菌数量明显增加(P＜0.01),肠杆菌、肠球菌数量无明显变化(P＞0.05).[结论]MOS能有效调节肠道菌群,增殖双歧杆菌及乳杆菌.     

滋肾清肝方对2型糖尿病胰岛素抵抗大鼠糖脂代谢的影响

目的 探讨滋肾清肝方对2型糖尿病大鼠糖脂代谢的影响.方法 大鼠高糖高脂饲料喂养4周后,腹腔注射30 mg/kg链脲佐菌素建立2型糖尿病大鼠模型,并随机分为糖尿病模型对照组、滋肾清肝方低剂量组[灌胃（ig） 250 mg/（kg·d）]、中剂量组[ig 500 mg/（kg·d）]、高剂量组[ig 750 mg/（kg·d）]及罗格列酮治疗组[ig 4mg/（kg ·d）].以滋肾清肝方低、中、高剂量持续给药30 d后测空腹血糖、血脂、糖化血红蛋白、胰岛素水平并行口服糖耐量试验.结果 与模型组比较,应用滋肾清肝方大鼠空腹血糖、糖化血红蛋白、甘油三酯、总胆固醇、低密度脂蛋白及糖耐量试验中糖负荷后120 min血糖显著降低（P均＜0.05）,高密度脂蛋白和胰岛素、胰岛素敏感指数显著升高（P均＜0.05）.结论 滋肾清肝方能有效地降低2型糖尿病模型大鼠的血糖,改善脂代谢紊乱.     

罗格列酮联合阿托伐他汀对小鼠肝脏ABCA1 mRNA表达的影响

将18只雄性昆明小鼠随机分为三组,A组每早用阿托伐他汀5mg／kg灌胃,B组每早用阿托伐他汀5mg／kg＋罗格列酮1mg／kg灌胃,对照组用相同剂量的生理盐水灌胃。用RT-PCR法和免疫组化法检N-组肝脏ATP结合盒转运子A1（ABCA1）mRNA和蛋白表达。结果显示,与对照组肝脏ABCA1mRNA比较,A组降低,B组升高（P〈0．05）。提示罗格列酮联合阿托伐他汀能提高小鼠肝脏ABCA1mRNA的表达。     

黄萸消渴胶囊对糖尿病鼠的降糖作用

目的 探讨黄萸消渴胶囊对糖尿病鼠降糖的作用及其机制.方法 雄性Wistar大鼠及雄性昆明种小鼠各60只,以55 mg/kg 四氧嘧啶由尾静脉注射,建立糖尿病模型,选择造模成功且血糖值相近的鼠40只,随机分为4组(每组10只);模型组、降糖灵组(50 mg/kg)、黄萸消渴胶囊(1.0 g/kg、2.0 g/kg)两组;另设正常对照组,连续灌服14 d,分别检测各组血糖、血脂及采用放射免疫法测定血清胰岛素含量.同时对正常大鼠一次灌服黄萸消渴胶囊进行糖耐量实验.结果 黄萸消渴胶囊具有明显降低糖尿病鼠血糖、血脂的作用,并能提高血清胰岛素的含量,对正常大鼠糖耐量没有显著影响.结论 黄萸消渴胶囊降糖作用与改善胰岛β细胞的功能并刺激胰岛β细胞释放胰岛素有关.     

大黄酸和罗格列酮对db/db糖尿病小鼠代谢紊乱和肾脏损伤的作用比较

目的:比较大黄酸和罗格列酮对糖尿病db/db小鼠代谢紊乱和肾脏损伤的作用,探讨大黄酸防治糖尿病肾病的机制.方法:实验小鼠分四组:db/m正常小鼠对照组;db/db糖尿病小鼠对照组;db/db糖尿病小鼠大黄酸[120 mg/(Kg·d)]台疗组;db/db糖尿病小鼠罗格列酮[4 m/g(Kg·d)]治疗组.连续灌胃12周,于实验末比较各组体重、血糖和血脂水平.PAS染色、免疫荧光分析肾小球病理形态学改变.电镜分析线粒体数目形态改变.Real-time PCR分析脂肪和肌肉组织过氧化物酶体增生物激活受体γ(PPARγ)、胰岛素抵抗因子(resistin)和脂肪酸转运体(FAT/CD36)mRNA表达.结果:大黄酸和罗格列酮治疗均可明显降低db/db小鼠血糖水平.大黄酸治疗还可明显减轻体重,降低血胆固醇和三酰甘油水平,改善高脂血症;而罗格列酮治疗则增加小鼠体重,提高血胆固醇和低密度脂蛋白水平.组织学显示,db/db小鼠肾小球肥大,系膜区扩张,系膜基质增加,大量纤维连接蛋白;同时肾小管线粒体数目减少,体积增大,嵴结构不清.大黄酸和罗格列酮治疗后均可明显改善上述肾脏病理改变,但对线粒体的作用大黄酸较罗格列酮更为明显.db/db小鼠肌肉和脂肪组织PPARγ和resistin的表达均明显下降,FAT/CD36表达增加.大黄酸和罗格列酮治疗后,PPARγ表达增加,FAT/CD36表达下降,resistin在肌肉组织表达增加而在脂肪组织则表达继续下降.结论:大黄酸明显降低db/db糖尿病小鼠血糖,减轻肾脏组织学异常,其作用和胰岛素增敏剂罗格列酮类似,大黄酸改善脂代谢紊乱和治疗糖尿病肾病的作用明显优于罗格列酮.     

大黄素对2型糖尿病小鼠血糖、胰岛素水平的影响及机制探讨

目的观察大黄素对2型糖尿病糖尿病模型KKAy小鼠血糖及胰岛素水平的影响,并探讨其机制。方法血糖均均≥13.9 mmol/L的SPF级KKAy小鼠40只,随机分为模型组（灌服无菌水）、低、中、高剂量大黄素治疗组[分别予12.5、25、50 mg/（kg.d）大黄素灌胃]和吡格列酮治疗组[予1.95 mg/（kg.d）灌胃],连续给药8周。8周后测定各组小鼠空腹血糖（FPG）、空腹胰岛素（FINS）,并计算胰岛素敏感指数（ISI）;用RT-PCR法测定小鼠骨骼肌和脂肪组织中PI3-K及GluT4的mRNA。结果与模型组比较,低、中、高剂量大黄素治疗组和吡格列酮治疗组小鼠的FPG、FINS、ISI均明显降低（P均〈0.05）,且呈剂量依赖性。高剂量大黄素治疗组组FINS、ISI均高于吡格列酮治疗组（P均〈0.05）。与模型组相比,低、中、高剂量大黄素治疗组及吡格列酮治疗组小鼠PI3-K、GluT4的mRNA明显增高（P均〈0.05）。结论大黄素具有良好的降血糖、降低胰岛素水平和提高胰岛素敏感度作用,其机制可能与PI3-K、GluT4基因有关。     

代谢相关性脂肪性肝病小鼠不同高脂饮食时期血糖水平和肠道菌群变化动态分析

目的 探讨在不同高脂饮食喂养时期代谢相关性脂肪性肝病(MAFLD)小鼠血糖水平和肠道菌群的动态变化.方法 采用高脂食物饲喂12只C57BL/6小鼠24周,分别在喂养0周、8周、16周和24周行葡萄糖耐量试验(GTT)和胰岛素耐受试验(ITT).采集小鼠粪便进行16sRNA检测,分析肠道细菌结构和肠道菌群多样性的变化.结...     

罗格列酮和二甲双胍治疗对胰岛素抵抗KKAy糖尿病小鼠肝及横纹肌组织PTEN蛋白表达的影响

目的观察罗格列酮和二甲双胍治疗后胰岛素抵抗KKAy糖尿病小鼠肝及横纹肌组织PTEN蛋白表达的变化。方法 KKAy小鼠制备糖尿病模型后随机分为未治疗组、罗格列酮治疗组及二甲双胍治疗组。C57BL小鼠普通饲料喂养,为对照组。4周后处死小鼠,Western blot检测肝及横纹肌PTEN蛋白、胰岛素刺激后磷酸化473Akt的表达并进行定量分析。结果罗格列酮及二甲双胍处理后KKAy糖尿病小鼠肝及横纹肌组织磷酸Akt升高倍数与KKAy糖尿病小鼠相比均无明显变化(P0.05),罗格列酮和二甲双胍处理后肝及骨骼肌PTEN蛋白表达与糖尿病未治疗组相比差异没有统计学意义(P0.05)。结论罗格列酮和二甲双胍不会影响PI3k-Akt通路活性及PTEN蛋白的表达,两者改善血糖和胰岛素抵抗可能与胰岛素敏感组织PTEN蛋白的表达无关。     

Expression Analysis of cPLA2 Alpha Interacting TIP60 in Diabetic KKAy and Non-Diabetic C57BL Wild-Type Mice: No Impact of Transient and Stable TIP60 Overexpression on Glucose-Stimulated Insulin Secretion in Pancreatic Beta-Cells

In the present study we investigate the expression levels of cytosolic phospholipase A2 α (cPLA2α) interacting histone acetyl transferase proteins TIP60α and TIP60β in non-diabetic C57BL wild-type mice and obese type 2 diabetic KKAy model mice. The aim was to test our hypothesis that TIP60 plays a regulatory role in glucose-stimulated insulin secretion from pancreatic β-cells. MATERIAL AND METHODS: Ten obese diabetic KKAy mice and ten non-diabetic C57BL mice were fed a standard chow diet. After nine weeks, islet RNA was purified and used to measure TIP60 expression. We investigated the effect of TIP60α and TIP60β on glucose-stimulated insulin secretion by transient and stable overexpression in the pancreatic mouse β-cell line MIN6 and the rat β-cell line INS-1E. RESULTS: We found that non-diabetic C57BL mice and diabetic KKAy mice have the same level of both the α and β splice forms of TIP60. Furthermore, we demonstrated that transient and stable expression of TIP60 in INS-1E cells affects neither glucose-stimulated insulin secretion, insulin output nor cell insulin content. Also susceptibility to developing gluco-toxicity was unaffected. CONCLUSION: TIP60 over-expression does not affect glucose stimulated insulin secretion, insulin content or abnormal β-cell function during glucotoxicity.     

Rice bran extract prevents the elevation of plasma peroxylipid in KKAy diabetic mice

Oxidative stress is now considered to be a key factor in the development of diabetes and its complications. In this study, we examined the anti-oxidative effects of a crude lipophilic rice bran extract, Ricetrienol, which contains alpha-tocopherol, tocotrienol and phytosterol, in obese diabetic KKAy mice. We used KKAy mice fed a normal diet (DM group) or a diet including 0.1% Ricetrienol (RT group), and non-diabetic C57BL mice (C group). After 6 weeks, body weight, HbA1c, plasma glucose, lipids, peroxylipid (malonedialdehyde, MDA), alpha-tocopherol and glutathione peroxidase 1 (GPx) mRNA expression in the kidney were measured. At 1 week and at the end of the experimental period, urine 8-isoprostane and 8-hydroxy deoxyguanosine (8-OHdG) were also measured. Ricetrienol administration did not affect hyperglycemia, body weight or hyperlipidemia. Plasma MDA, urine 8-isoprostane and 8-OHdG in the DM group were significantly increased compared with the C group and the elevation of plasma MDA was significantly suppressed by 0.1% Ricetrienol. GPx mRNA expression was significantly increased in the RT group when compared with the C group. Plasma alpha-tocopherol in the RT group was significantly higher than that in the DM group. These findings suggest that Ricetrienol exerts a protective effect against oxidative damage in diabetes mellitus.     

同型半胱氨酸对KKAy小鼠心肌病变的影响

目的　观察高同型半胱氨酸 (Hcy)血症对糖尿病小鼠心肌的影响 ,以及补充叶酸对心肌病变的作用。方法　2 4只KKAy小鼠随机分成 3组 ,分别喂养高热量饮食 (KA组 )、高蛋氨酸饮食 (KB组 )以及高蛋氨酸加叶酸、维生素B1 2 饮食 (KC组 )。测定各组血浆Hcy、叶酸、维生素B1 2 水平 ,并观察心肌病理改变。结果　饲养 16周后 ,KB组血浆Hcy明显增高 [(2 9.33± 16 .85对 5 .33± 2 .0 3) μmol L ,P <0 .0 0 1],且心肌间质纤维化、钙化、小动脉管壁增厚、透明变性等病变加重 ,经叶酸、维生素B1 2 治疗的KC组血浆Hcy降至正常 (4 .0 4± 1.81) μmol L ,且心肌病变减轻。结论Hcy可以加重糖尿病小鼠的心肌病变 ,叶酸、维生素B1 2 可以有效减缓这一病变进程。     

Adipocyte-specific reduction of phosphodiesterase 3B gene expression and its restoration by JTT-501 in the obese, diabetic KKAy mouse.

OBJECTIVE: Phosphodiesterase (PDE) 3B is a key enzyme involved in the anti-lipolytic action of insulin in adipocytes. PDE3B activation results in a reduced output of free fatty acids (FFA), whereas elevated serum FFA is known to cause insulin resistance. We have recently reported that reduced PDE3B gene expression is restored by treatment with pioglitazone, in the adipose tissues of obese, insulin-resistant diabetic KKAy mice. To determine whether the altered PDE3B gene expression is specific for adipocytes, the expression of this gene in liver and epididymal fat tissues of KKAy mice was examined. The effect of JTT-501, another peroxisome proliferator-activated receptor (PPAR)gamma ligand, which is different from thiazolidinedione, was also examined. METHODS: PDE3B mRNA and protein were quantified by an RNase protection assay and Western blotting respectively. Membrane-bound PDE activities were also measured. RESULTS: In adipose tissues of KKAy mice, PDE3B mRNA, protein and membrane-bound PDE activity were reduced to 47%, 57% and 51% respectively relative to those in C57BL/6J control mice. JTT-501 increased PDE3B mRNA, protein and membrane-bound PDE activity by 2.2-, 1.6- and 1.7-fold respectively over those of untreated KKAy mice. In the liver, PDE3B gene expression remained unchanged in KKAy mice, and was not affected by JTT-501. JTT-501 reduced the elevated levels of serum insulin, glucose, FFA and triglyceride in KKAy mice. CONCLUSIONS: PDE3B gene expression was specifically reduced in the adipose tissues of KKAy mice. JTT-501 restored this reduced gene expression with an accompanying improvement in elevated serum FFA and insulin resistance.     

The KKAy mouse: a model for the rapid development of glomerular capillary basement membrane thickening

The renal tissue of 12-, 29-, 90- and 165-day-old genetically obese, hyperphagic, diabetic KKAy and age-matched nondiabetic C57BL/6 mice was morphometrically analyzed to characterize the development of peripheral glomerular capillary basement membrane thickening in the kidney of this animal model. Peripheral glomerular basement membrane (GBM) thickness was unremarkable in KKAy mice at 12 days of age (prior to onset of hyperinsulinemia) or at 29 days of age (after development of hyperinsulinemia). By 90 days of age, when the KKAy mice became severely hyperinsulinemic and hyperglycemic, the peripheral GBM thickness was greater (13%, p less than 0.002) in the diabetic compared with the nondiabetic mice. Furthermore, the peripheral GBM thickness was exacerbated (20%, p less than 0.001) by 165 days of age in the KKAy mice. The results of the present study suggest that peripheral glomerular capillary basement membrane thickening has an early onset and develops rapidly in the KKAy mouse in comparison with other diabetic animal models. Therefore, the KKAy mouse seems to be an appropriate model for further investigation of early structural and functional defects in the glomerular filtration barrier.     

Apolipoprotein A-IV improves glucose homeostasis by enhancing insulin secretion

Apolipoprotein A-IV (apoA-IV) is secreted by the small intestine in response to fat absorption. Here we demonstrate a potential role for apoA-IV in regulating glucose homeostasis. ApoA-IV-treated isolated pancreatic islets had enhanced insulin secretion under conditions of high glucose but not of low glucose, suggesting a direct effect of apoA-IV to enhance glucose-stimulated insulin release. This enhancement involves cAMP at a level distal to Ca(2+) influx into the β cells. Knockout of apoA-IV results in compromised insulin secretion and impaired glucose tolerance compared with WT mice. Challenging apoA-IV(-/-) mice with a high-fat diet led to fasting hyperglycemia and more severe glucose intolerance associated with defective insulin secretion than occurred in WT mice. Administration of exogenous apoA-IV to apoA-IV(-/-) mice improved glucose tolerance by enhancing insulin secretion in mice fed either chow or a high-fat diet. Finally, we demonstrate that exogenous apoA-IV injection decreases blood glucose levels and stimulates a transient increase in insulin secretion in KKAy diabetic mice. These results suggest that apoA-IV may provide a therapeutic target for the regulation of glucose-stimulated insulin secretion and treatment of diabetes.     

Treatment of insulin-resistant mice with the oral antidiabetic agent pioglitazone: evaluation of liver GLUT2 and phosphoenolpyruvate carboxykinase expression.

Obese KKAy insulin-resistant mice represent a model for the human syndrome of noninsulin-dependent diabetes mellitus. As such, the animals are hyperglycemic and hyperinsulinenic. Treatment of KKAy mice with pioglitazone, a new antihyperglycemic agent, lowered elevated blood glucose and insulin levels to near normal. Since hepatic glucose overproduction is a key abnormality in noninsulin-dependent diabetes mellitus, the aim of the present study was to define the specific effects of pioglitazone on hepatic glucose metabolism and release. To do so, we evaluated the expression of the major liver glucose transporter, GLUT2, and examined the activity and expression of the major rate-limiting enzyme for gluconeogenesis, phosphoenolpyruvate carboxykinase. Our results showed that GLUT2 mRNA abundance was unchanged in diabetic KKAy mice compared to nondiabetic animals, and that no changes were elicited by pioglitazone treatment. Such unaltered GLUT2 levels were consistent with a role for liver GLUT2 in bidirectional transport of glucose during physiological states of uptake or release. In contrast, phosphoenolpyruvate carboxykinase activity and mRNA abundance were concordantly elevated 2-fold in diabetic animals and were returned to normal levels after treatment with pioglitazone. Given that pioglitazone therapy led to decreased hepatic gluconeogenesis while insulin levels were concomitantly lowered, it appeared that pioglitazone acted to restore sensitivity to insulin's normal inhibitory actions.     

链脲佐菌素诱导2型糖尿病大鼠的心肌损伤观察及机制初探

目的观察链脲佐菌素（STZ）诱导2型糖尿病后不同时期大鼠心肌损伤及凋亡的程度,并对其机制进行分析。方法使用高糖、高脂加STZ注射造成大鼠2型糖尿病模型,于STZ注射后不同时间点分批处死动物,对心肌损伤及凋亡指标进行测定。结果糖尿病大鼠经STZ处理1周后,与对照组大鼠相比,空腹血糖明显升高（FBG≥16．7mmol／L）,而血清胰岛素含量升高或无明显变化,提示2型糖尿病造模成功。糖尿病大鼠第12周起LVSP、＋dp／dtmax、-dp／dtmax显著降低,提示糖尿病可引起心功能下降。糖尿病大鼠第2周、4周和12周CK—MB明显增高,第12周和24周cTnI明显增高,提示糖尿病第2周即可诱发心肌损伤,并随着病程的发展加重。凋亡指标测定表明,糖尿病大鼠在第4周和12周时,caspase-3和caspase-8活性显著增高,第12周和24周时caspase-9活性显著增高,提示糖尿病第4周即可造成心肌细胞凋亡,且可能依赖caspase-8途径早于依赖caspase-9途径。结论糖尿病可以引起心肌损伤和细胞凋亡,并随病程的延长而加重,这种凋亡与caspase-8和caspase-9依赖的凋亡途径有关。