牛大力多糖对糖尿病小鼠降血糖作用的研究

目的研究牛大力多糖对糖尿病模型小鼠的降血糖作用。方法采用链脲佐菌素(STZ)诱导糖尿病小鼠模型,使用低、中、高剂量牛大力多糖对模型小鼠进行干预,分别比较牛大力多糖干预组、模型组及对照组小鼠空腹血糖(FBG)、空腹胰岛素(FINS)及肝糖原含量。结果牛大力多糖可以显著降低STZ诱导的糖尿病小鼠FBG水平(P <0.01),提高模型小鼠FINS水平和肝糖原含量(P <0.01)。结论牛大力多糖可显著降低糖尿病小鼠血糖水平,其作用机制可能与增加胰岛素分泌,促进糖原合成有关。     

阳桃根多糖对糖尿病小鼠胰岛素及胸、脾指数的影响

目的：观察阳桃根多糖对链脲佐菌素（streptozocin,STZ）诱导的糖尿病小鼠血清胰岛素及胸腺、脾脏指数的影响。方法：建立由链脲佐菌素诱导的糖尿病小鼠模型,将阳桃根多糖高、低剂量组、格列本脲组分别灌胃给药14d,另设模型组、正常对照组灌胃生理盐水。检测小鼠的空腹血糖值（FBG）、血清胰岛素（INS）、胰岛素敏感指数;测定小鼠胸腺指数及脾指数。结果：与模型组比较,阳桃根多糖高、低剂量组均能显著降低糖尿病小鼠的空腹血糖（P〈0．01）、空腹血清胰岛素（P〈0．01）,提高胰岛素敏感指数（P〈0．01）、并能明显提高小鼠胸腺指数及脾指数（P〈0．01）。结论：阳桃根多糖能显著降低STZ致糖尿病小鼠的FBG,改善糖尿病小鼠对胰岛素的敏感性,并增强糖尿病小鼠的免疫功能。     

糖脉交泰胶囊对高糖高脂糖尿病大鼠糖脂代谢及肝脏葡萄糖激酶、低密度脂蛋白受体的影响

目的研究糖脉交泰胶囊对高糖高脂糖尿病大鼠糖脂代谢及肝脏葡萄糖激酶(GCK)、低密度脂蛋白受体(LDLR)蛋白表达的影响。方法高糖高脂饮食加小剂量链脲佐菌素(STZ,35 mg.kg-1)联合诱导制备高糖高脂糖尿病大鼠模型,并随机分组为正常对照组、模型组、糖脉交泰组和吡格列酮组,每组8只,给予相应的药物治疗4周。实验结束后比较各组空腹血糖值(FBG)、糖化血清蛋白(GSP)、糖化血红蛋白(HbA1c)、血清总胆固醇(TC)、甘油三脂(TG)、低密度脂蛋白(LDL-C)、高密度脂蛋白(HDL-C)及肝糖原等指标;Western blot法检测肝脏组织中GCK和LDLR蛋白表达。结果与模型组比较,糖脉交泰胶囊能明显降低大鼠FBG、HbA1c、GSP水平,明显改善TC、TG、LDL-C等指标(P<0.05);肝脏肝糖原含量及LDLR和GCK的蛋白表达均明显增加(P<0.05)。结论糖脉交泰胶囊具有明显的调节糖脂代谢的作用,其作用机制与其提高肝糖原的含量,增加肝脏GCK和LDLR蛋白表达相关联。     

虫草多糖对2型糖尿病小鼠InsR／IRS-1通路及糖代谢的影响

目的：观察虫草多糖对2型糖尿病小鼠InsR／IRS—1通路及糖代谢的影响。方法：采用高脂饲料联合腹腔注射小剂量链脲佐菌素（STZ,25mg·kg-1）建立胰岛素抵抗2型糖尿病模型,每日给予不同剂量虫草多糖（200,400mg·kg-1）治疗,28d后．免疫印迹法检测实验小鼠骨骼肌内胰岛素受体（1nsR）、胰岛素受体底物（IRS-1）及葡萄糖转运蛋白（GLUT4）的表达水平。检测肝脏葡萄糖激酶（GK）、磷酸果糖激酶（PFK）活性水平。结果：虫草多糖治疗组可显著改善糖尿病小鼠InsR／IRS一1及GLUT4蛋白的畀常表达（P〈0．05）;并呈剂量依赖性地增强小鼠肝脏GK及PFK酶活性,与糖尿病模型组比较差畀有统计学意义（P〈0．05或0．01）。结论：虫草多糖可增强胰岛素信号通路敏感性,改善葡萄糖代谢,从而缓解糖尿病小鼠胰岛素抵抗及高血糖症状,为胰岛素抵抗2型糖尿病的临床治疗提供新的依据。     

人工虫草碱提取物的降血糖作用研究

人工虫草菌丝的碱(1.25 mol·L~(-1)NaOH)提醇沉淀物CsOH(产率2.58％)经纸层析(PPC)和气相层析分析证实为含5种单糖的杂多糖。口服给予CsOH在剂量500、250mg·kg~(-1)时和腹腔给予CsOH在剂量100、50 mg·kg~(-1)时对正常小鼠、四氧嘧啶糖尿病模型小鼠和链脲佐菌素糖尿病模型小鼠均有显著的降血糖作用.且呈现一定的量效关系。     

沙棘粗多糖对正常和造模糖尿病小鼠血糖影响的研究

目的探讨沙棘粗多糖对正常小鼠耐糖量的影响,以及对造模糖尿病小鼠高血糖的影响。方法采用小鼠耐糖量模型,以沙棘粗多糖为实验药物,观察其对蔗糖、葡萄糖、麦芽糖、淀粉负荷剂量后的正常小鼠血糖影响;分别用四氧嘧啶、链脲佐菌素诱发实验性糖尿病动物模型,不同剂量的沙棘粗多糖灌胃,观察对高血糖小鼠血糖的影响。结果小鼠耐糖量模型组与对照组比较,淀粉组血糖值降低较为明显(P<0.01),蔗糖组次之(P<0.05);与四氧嘧啶(链脲佐菌素)模型组比较,给药2周和4周后,沙棘粗多糖高剂量组对高血糖小鼠降糖作用明显(P<0.01,P<0.05),降糖率分别为31.72%(33.14%)和45.70%(43.78%),沙棘粗多糖低剂量组降糖作用次之(P<0.05,P<0.05),降糖率分别为28.02%(27.07%)和39.38%(36.43%)。结论沙棘粗多糖能够提高正常小鼠的耐糖量;沙棘粗多糖对四氧嘧啶和链脲佐菌素致高血糖小鼠具有良好的降血糖作用,且作用强度与剂量呈相关性。     

基于TNF-α和FABP4蛋白探究长期服用奥氮平导致胰岛素抵抗的作用机制

目的：探究在长期服用奥氮平诱导的胰岛素抵抗过程中，TNF-α和FABP4的相互作用。方法：选择SD大鼠连续灌胃给予奥氮平8周，建立奥氮平诱导胰岛素抵抗的大鼠模型，期间分别对大鼠体质量、空腹血糖（FBG）、空腹胰岛素（Fins）和胰岛素抵抗指数（HOMA-IR）进行测定比较；ELISA测定大鼠血清和白色脂肪中的TNF-α表达量；通过Western Blot对3T3-L1细胞模型中的研究蛋白（FABP4和GLUT4）进行分析比较。结果：与对照组相比，长期服用奥氮平诱导胰岛素抵抗的大鼠血清和白色脂肪内TNF-α表达量显著升高（P<0.05），且在3T3-L1脂肪细胞模型中，随着TNF-α浓度增加，FABP4的表达量显著上升（P<0.05），GLUT4的上膜量显著降低（P<0.05）。结论：长期服用奥氮平可能引起机体产生炎症反应，激活TNF-α的表达，进而上调FABP4蛋白，最终降低GLUT4上膜量，导致胰岛素抵抗的发生。     

益气养阴活血方对糖尿病肾病大鼠NFAT2/COX-2的影响

目的:探讨益气养阴活血方对糖尿病肾病(DN)大鼠肾脏保护作用及其机制。方法:50只雄性SD大鼠随机分为正常组8只、造模组42只。除正常组外,造模组腹腔注射链脲佐菌素(STZ)诱导建立DN大鼠模型,造模成功的32只DN大鼠随机分为模型组、缬沙坦组、益气养阴活血方低剂量组及益气养阴活血方高剂量组,每组8只。灌胃6周后全自动生化分析仪检测各组大鼠血肌酐(Scr)、尿素氮(BUN)、空腹血糖(FBG)、24 h尿蛋白总量(24 h-UTP);Western blot及荧光定量PCR分别检测肾脏NFAT2、COX-2相关蛋白及其mRNA表达;苏木素-伊红(HE)染色观察大鼠肾脏病理变化。结果:与正常组比较,模型组大鼠肾小球、肾小管病理损伤较重,血清Scr、BUN、FBG、24 h-UTP、肾组织NFAT2、COX-2相关蛋白及其mRNA表达水平均升高(P＜0.01);与模型组比较,益气养阴活血方干预组大鼠肾脏病理明显改善,血清Scr、BUN、FBG、24 h-UTP、肾组织NFAT2、COX-2相关蛋白及其mRNA表达水平均降低(P＜0.01,P＜0.05)。结论:益气养阴活血方可能通过下调NFAT2/COX-2信号通路而减轻肾脏病理损害,保护肾功能,降低尿蛋白。     

1型糖尿病裸鼠模型的制作和成模后的注意事项

目的:探讨链脲佐菌素腹腔注射制作1型糖尿病小鼠模型的最佳剂量.方法:Balb/c裸鼠40只随机分为正常对照组(A组)及175、200、225 mg/kg链脲佐菌素组(B、C、D组).腹腔注射不同剂量链尿佐菌素诱导小鼠糖尿病作为动物模型.血糖仪检测小鼠血糖变化,光镜观察胰岛的组织学改变情况.结果:对照组血糖基本无变化,模型组血糖值随时间增加而增加.不同桌量链脲佐菌素诱导小鼠胰岛β细胞损伤的病理改变和程度均有所差异.结论:3种剂量链脲佐菌素均可诱导不同程度的1型糖尿病发生.以链脲佐菌素200mg/kg诱导的1型糖尿病的效果为最佳.     

乌饭树叶黄酮对糖尿病小鼠胰岛形态和功能的影响

目的：探讨乌饭树叶黄酮对链脲佐菌素诱导的糖尿病小鼠的胰岛形态和功能的影响。方法：采用昆明小鼠作为研究对象,以静脉注射链脲佐菌素致小鼠体内诱导形成糖尿病模型。造模成功后将糖尿病小鼠随机分为模型对照组、二甲双胍对照组、80 mg·kg^-1·d^-1和160 mg·kg^-1·d^-1乌饭树叶黄酮组,另设有空白对照组。随后各组小鼠连续给予相应药物14 d。末次给药后,各组小鼠经过夜禁食,测其空腹血糖水平,而后收集小鼠血清和胰腺标本。ELISA法检测血清胰岛素;胰腺组织制备匀浆用于超氧化物歧化酶（superoxide dismutase,SOD）、谷胱甘肽过氧化物酶（glutathione peroxidase,GSH-Px）的活性和丙二醛（malondialdehyde,MDA）含量;测定胰腺组织中肿瘤坏死因子α（tumor necrosis factor-α,TNF-α）和白细胞介素6（interleukin 6,IL-6）水平;并以HE染色及透射电镜观察胰岛组织病理学和超微结构变化。结果：与模型组相比较,糖尿病小鼠经乌饭树叶黄酮干预后空腹血糖有不同程度下降（P<0.05）;乌饭树叶黄酮受试组的血清胰岛素含量明显比模型对照组高（P<0.05）;与模型对照组比较,乌饭树叶黄酮组的胰腺组织中SOD和GSH-Px活性显著升高,MDA含量则明显下降,与此同时,炎症因子TNF-α和IL-6也明显下降。糖尿病小鼠的胰腺组织病理形态学和超微机构改变也在经乌饭树叶黄酮干预后有所改善。结论：乌饭树叶黄酮可降低糖尿病小鼠血糖,该作用可能与其能改善糖尿病小鼠血脂代谢和胰腺组织的氧化应激状态进而减少炎症反应有关。     

Antihyperglycemic and antihyperlipidemic action of Cinnamomi Cassiae (Cinnamon bark) extract in C57BL/Ks db/db mice

In previous study, the anti-diabetic effect of Cinnamomi Cassiae extract (Cinnamon bark: Lauraceae) in a type II diabetic animal model (C57BIKsj db/db) has been reported. To explore their mechanism of action, in present study, the effect of cinnamon extract on anti-hyperglycemia and anti-hyperlipidemia was evaluated by measuring the blood glucose levels, serum insulin, and adiponectin levels, serum and hepatic lipids, PPARα mRNA expression in liver and PPARγ mRNA expression in adipose tissue, respectively. Male C57BIKs db/db mice were divided into a diabetic group and cinnamon extract treated group and examined for a period of 12 weeks (200 mg/kg, p.o). The fasting blood glucose and postprandial 2 h blood glucose levels in the cinnamon treated group were significantly lower than those in the control group (p < 0.01), whereas the serum insulin and adiponectin levels were significantly higher in the cinnamon treated group than in the control group (p < 0.05). The serum lipids and hepatic lipids were improved in the cinnamon administered group. Also the PPARα mRNA (liver) and PPARγ mRNA (adipose tissue) expression levels were increased significantly in the cinnamon treated group (p < 0.05). Our results suggest that cinnamon extract significantly increases insulin sensitivity, reduces serum, and hepatic lipids, and improves hyperglycemia and hyperlipidemia possibly by regulating the PPAR-medicated glucose and lipid metabolism.     

Hypoglycemic effects of Ganoderma lucidum polysaccharides in type 2 diabetic mice

Our aims were to investigate the hypoglycemic effects and mechanisms of action of Ganoderma lucidum polysaccharides (GLPs) administered for 7 days in type 2 diabetic mice. The mice were randomly divided into four groups (8 mice/group): normal control group, diabetic control group, low-dose GLP-treated diabetic group (50 mg/kg/d), and high-dose GLP-treated diabetic group (100 mg/kg/d). Diabetes was induced by streptozotocin injection and high-fat dietary feeding. At the end of the study, fasting serum glucose, insulin, body weight (BW) and epididymal white adipose tissue weight were measured. The hepatic mRNA levels of glycogen phosphorylase (GP), fructose-1,6-bisphosphatase (FBPase), phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) genes were determined by real-time polymerase chain reaction. Both doses of GLPs significantly decreased fasting serum glucose, insulin and epididymal fat/BW ratio compared with the diabetic control group (p < 0.05). The hepatic mRNA levels of GP, FBPase, PEPCK and G6Pase were significantly lower in both GLP-treated groups compared with the diabetic control group. Taken together, GLPs significantly decrease fasting serum glucose levels in type 2 diabetic mice in a dose-dependent manner. The decreases in fasting serum glucose levels may be associated with decreased mRNA expression levels of several key enzymes involved in gluconeogenesis and/or glycogenolysis.     

Antihyperglycemic action of isoferulic acid in streptozotocin-induced diabetic rats

Wistar rats with streptozotocin-induced diabetes (STZ-diabetic rats), which is similar to human insulin-dependent diabetic mellitus (IDDM), were employed to investigate the antihyperglycemic action of isoferulic acid. A single intravenous injection of isoferulic acid decreased the plasma glucose in a dose-dependent manner in the STZ-diabetic rats. Repeated intravenous administration of STZ-diabetic rats with isoferulic acid (5.0 mg kg(-1)) also resulted in the lowering of plasma glucose after one day. Stimulatory effects of isoferulic acid on the glucose uptake and glycogen synthesis in soleus muscles isolated from STZ-diabetic rats were also obtained indicating an increase of glucose utilization following isoferulic acid treatment which was not dependent on insulin. The mRNA level of glucose transporter subtype 4 form (GLUT4) in soleus muscle was raised by isoferulic acid after repeated treatment for 1 day in STZ-diabetic rats. Similar repeated treatment with isoferulic acid reversed the elevated mRNA level of phosphoenolpyruvate carboxykinase (PEPCK) in liver of STZ-diabetic rats to the normal level. However, expression of GLUT4 and PEPCK genes in nondiabetic rats were not influenced by similar treatment with isoferulic acid. These results suggest that isoferulic acid can inhibit hepatic gluconeogenesis and/or increase the glucose utilization in peripheral tissue to lower plasma glucose in diabetic rats lacking insulin.     

Molecular mechanisms of action of styrene toxicity in blood plasma and liver

Styrene is an aromatic colorless hydrocarbon available in liquid form and highly volatile. In its pure form, it gives a sweet smell. The primary source of exposure in the environment is from plastic materials, rubber industries, packaging materials, insulations, and fiber glass and carpet industry. Natural sources of styrene include: few metabolites in plants which are transferred through food chain. The current study was designed to evaluate styrene toxicity, including: superoxide dismutase (SOD) and protein carbonyl, oxidative stress, glucose‐6‐phosphatase (G6Pase), glycogen phosphorylase (GP), and phosphoenolpyruvate carboxykinase (PEPCK) activities, adenosine triphosphate (ATP) to adenosine diphosphate (ADP) ratio, and changes in gene expressions such as glutamate dehydrogenase 1 (GLUD1), glucose transporter 2 (GLUT2), and glucokinase (GCK) in the rat liver tissue. For this purpose, styrene was dissolved in corn oil and was administered via gavage, at doses 250, 500, 1000, 1500, 2000, mg/kg/day per mL and control (corn oil) to each rat with one day off in a week, for 42 days. Plasma SOD and protein carbonyl of plasma were significantly up‐regulated in 1000, 1500, and 2000 mg/kg/day styrene administrated groups (P < .001). In addition, styrene caused an increase in lipid peroxidation (LPO) and reactive oxygen species (ROS) in the dose‐dependent manners in liver tissue (P < .001). Furthermore, the ferrous reducing antioxidant power (FRAP) and total thiol molecules (TTM) in styrene‐treated groups were significantly decreased in liver tissue (P < .001) with increasing doses. In treated rats, styrene significantly increased G6Pase activity (P < .001) and down‐regulated GP activity (P < .001) as compared to the control group. The PEPCK activity was significantly raised in a dose‐dependent manner (P < .001). The ATP/ADP ratio of live cells was significantly raised by increasing the dose (P < .001). There was significantly an up‐regulation of GLUD1 and GCK at 2000 mg/kg group (P < .01) and a down‐regulation for GLUT2 at the same dose. While in the rest of group, GLUT2 showed up‐regulation of relative fold change. By targeting genes such as GLUD1, GLUT2, and GCK, disruption of hepatic gluconeogenesis, glycogenolysis, and insulin secretory functions are obvious. The present study illustrates that induction of oxidative stress followed by changes in G6Pase, GP, and PEPCK activities and the genes responsible for glucose metabolism are the mechanisms of styrene's action in the liver.     

Mechanism of the hypoglycemic effect of stevioside, a glycoside of Stevia rebaudiana

We have studied the effects of stevioside on the glucose and insulin metabolism in 2 models of diabetes in rats, STZ-induced diabetic rats and NIDDM diabetic rats induced by feeding with fructose. Stevioside (0.5 mg/kg), lowered the blood glucose levels in STZ-induced diabetic rats, peaking at 90 min. Stevioside administered twice daily also demonstrated dose-dependent effects in lowering the glucose levels in both diabetic rat models. Stevioside reduced the rise in glucose during glucose tolerance testing in normal rats. Stevioside dose-dependently decreased protein levels of phosphoenol pyruvate carboxykinase (PEPCK) and PEPCK mRNA after 15 days of treatment. Stevioside also reduced insulin resistance in the diabetic animals as shown by the glucose lowering effects of tolbutamide. In conclusion, stevioside was able to regulate blood glucose levels by enhancing not only insulin secretion, but also insulin utilization in insulin-deficient rats; the latter was due to decreased PEPCK gene expression in rat liver by stevioside's action of slowing down gluconeogenesis. Further studies of this agent for the treatment of diabetes appear warranted.     

Antidiabetic effects of cinnamon oil in diabetic KK-Ay mice

The hypoglycemic effect of cinnamon oil (CO) in a type 2 diabetic animal model (KK-A^y mice) was studied. The main component of CO was cinnamaldehyde, and other nineteen components were also determined. CO was administrated at doses of 25, 50 and 100 mg/kg for 35 days. It was found that fasting blood glucose concentration was significantly decreased (P < 0.05) with the 100 mg/kg group (P < 0.01) the most efficient compared with the diabetic control group. In addition, there was significant decrease in plasma C-peptide, serum triglyceride, total cholesterol and blood urea nitrogen levels while serum high density lipoprotein (HDL)-cholesterol levels were significantly increased after 35 days. Meanwhile, glucose tolerance was improved, and the immunoreactive of pancreatic islets β-cells was promoted. These results suggest that CO had a regulative role in blood glucose level and lipids, and improved the function of pancreatic islets. Cinnamon oil may be useful in the treatment of type 2 diabetes mellitus.     

小檗碱改善2型糖尿病大鼠胰岛素抵抗与PI-3K、GLUT4蛋白相关性的研究

目的观察小檗碱对2型糖尿病大鼠骨骼肌组织磷脂酰肌醇3激酶(phosphatidylinositol-3-kinase,PI-3K)之p85亚基、葡萄糖转运子4(glucose transporter4,GLUT4)蛋白表达的影响,以探讨小檗碱改善胰岛素抵抗,防治2型糖尿病的分子机制。方法采用尾静脉注射小剂量链脲佐菌素(streptozotocin,STZ,30mg.kg-1)加高脂高热量饲料喂养的方法建立2型糖尿病大鼠模型,以小檗碱干预10wk,检测血糖和血清胰岛素,用Western blot方法检测小檗碱干预后2型糖尿病大鼠骨骼肌组织PI-3K之p85亚基、GLUT4蛋白表达水平。结果小檗碱干预的2型糖尿病大鼠骨骼肌组织PI-3K之p85亚基、GLUT4蛋白表达水平均较模型组显著增加。结论小檗碱对2型糖尿病的治疗效应可能与提高骨骼肌组织中PI-3K之p85亚基、GLUT4蛋白表达水平有关。     

吡格列酮对2型糖尿病大鼠血清炎症介质和糖耐量的影响

目的探讨吡格列酮对2型糖尿病大鼠炎症因子及其糖耐量水平的影响。方法8周龄健康Wistar大鼠,用链脲菌素（STZ）加高脂肪高热卡饮食诱导2型糖尿病大鼠模型,将糖尿病大鼠随机分为2组：糖尿病组（n=10）、吡格列酮组（n=10,10mg·kg-1．d-1,灌胃）,健康Wistar大鼠作为对照组（n=10）,糖尿病组和对照组给予同体积生理盐水灌胃,8周后分别测定空腹血糖（FBG）和胰岛素水平（FINS）,进行口服葡萄糖耐量试验（OGTT）,计算胰岛素抵抗指数（HOMA。IR）,测定大鼠血清中白介素1B（IL-1B）、白介素6（IL．6）、肿瘤坏死因子α（TNF-α）、急相反应蛋白C（CRP）水平。结果FBG、FINS和HOMA-R水平,糖尿病组比对照组显著升高（P〈0．05）,而吡格列酮可以明显降低糖尿病大鼠的水平,差异有统计学意义（P〈0．05）;OGTF实验结果显示：糖尿病大鼠餐后血糖水平明显升高（P〈0．05）,吡咯列酮明显减低糖尿病大鼠餐后血糖水平差异有统计学意义（P〈0．05）;IL-1β、IL-6、TNF-α、CRP水平与正常对照组比较糖尿病组显著升高（P〈0．05）,而吡格列酮可以明显降低糖尿病大鼠的水平,差异有统计学意义（P〈0．05）。结论吡格列酮可下调血清炎症因子的表达,改善胰岛素抵抗。