考察影响2型糖尿病小鼠血糖的因素

目的:考察四氧嘧啶(alloxan,ALX)诱导法制备2型糖尿病小鼠模型时影响血糖的因素.方法:120只昆明种小鼠,随机分为正常对照组和5个剂量的模型组,每组20只.正常对照组小鼠腹腔注射生理盐水,5个剂量的模型组小鼠分别腹腔注射250、200、150、100、50mg/kg的ALX,给药体积均为10 ml/kg,测量各组小鼠空腹血糖(FBG)的差异.考察体重(18.0～22.0g,22.1～ 28.0 g,28.1～35.0 g,n=20),饲养环境(是否有垫料,是否更换垫料,n=10)以及禁食时间(8、10、12、14、16 h,n=10)对FBG的影响,将FBG≥11.1 mmol/L的小鼠模型作为建模成功.计算各组小鼠的成模率和死亡率.结果:体重为22～28 g的小鼠腹腔注射ALX 100～ 150 mg/kg,夜间禁食12～ 14 h,无垫料的情况下饲养,可成功构建2型糖尿病小鼠模型.结论:该方法构建2型糖尿病小鼠模型成功率高,死亡率低,小鼠模型的血糖稳定.     

建立小鼠2型糖尿病模型时链脲佐菌素剂量的研究

目的：研究链脲佐菌素（STZ）注射剂量对建立2型糖尿病小鼠模型的影响。方法：不同文献中STZ的注射剂量不一致。本文以存活率和成模率两个因素为指标,采用高脂饲料喂养加不同浓度梯度的链脲佐菌素（STZ）注射建立2型糖尿病模型。结果：50mg/Kg剂量组小鼠虽然全部存活,成模率为0;100mg/Kg剂量组全部存活,成模率20%;150mg/Kg剂量组死亡率达70%,但存活下来的30%全部成模;200mg/Kg剂量组的小鼠全部死亡。结论：125mg/Kg是此方法中的STZ最佳剂量。     

高脂高糖饮食联合链脲佐菌素构建巴马小型猪2型糖尿病模型稳定性研究

目的应用高脂高糖饮食联合链脲佐菌素(STZ)构建巴马小型猪2型糖尿病(T2DM)模型,探讨STZ对巴马小型猪糖尿病成模的影响,为糖尿病相关研究提供安全稳定的动物模型。方法选用健康雄性巴马小型猪10只,随机分为2组:对照组5例,喂养普通饲料;糖尿病模型组5只,喂养高脂高糖饲料,上述2组共喂养10月。11月初糖尿病模型组腹腔注射STZ 100mg/kg,1周后重复1次;对照组腹腔注射等剂量柠檬酸-柠檬酸钠缓冲液。观察2组小型猪体质量、空腹血糖(FPG)、空腹胰岛素(FINS)水平,行胰腺组织病理学检查、胰岛B细胞免疫组织化学染色分析,同时计算胰岛素抵抗指数(HOMA-IR)。结果 1高脂高糖饲料喂养10月后,模型组小型猪体重、FBG、FINS及HOMA-IR高于对照组(P<0.01);2模型组STZ给药后(12月末试验结束时),与对照组相比,模型组的FPG进一步升高,FINS水平明显下降(P<0.01);3胰腺HE及免疫组织化学染色:成模组镜下胰岛整体形态萎缩,胰岛B细胞数目明显减少。结论采用高脂高糖饮食联合腹腔多次注射STZ可以成功构建巴马小型猪2型糖尿病模型,该方法操作简单、成模率高、稳定性较好。     

四氧嘧啶制备大鼠糖尿病不同给药方式比较

目的本文主要探讨两种给药方式对四氧嘧啶致大鼠糖尿病模型的影响,为制造稳定的大鼠糖尿病模型提供一种最佳选择。方法将80只大鼠随机分为A、B两组。A组大鼠分两次注射2%四氧嘧啶注射液,第一天120mg/kg,第二天100mg/kg;B组大鼠一次注射200mg/kg2%四氧嘧啶。造模七天后分别测各组大鼠血糖浓度。结果 A组大鼠造模成功25只,成功率62.5%,死亡4只,死亡率10%;B组大鼠造模成功17只,成功率42.5%,死亡9只,死亡率22.5%。两组大鼠实验数据比较差异有显著性。结论分次腹腔注射注射四氧嘧啶造模成功率高,死亡率低,是四氧嘧啶致大鼠糖尿病模型的最佳选择。     

银耳多糖J的慢性毒性实验

1 实验方法取18～22g体重的健康小白鼠30只,雌雄兼有,随机分为给药组与对照组,每组15只。给药方法:灌胃。给药容量:0.1ml/10g体重。给药剂量:前45d按1000mg/kg体重,2次/d。以后按2000mg/kg体重给药,1次/d,共180d。对照组给予同等容积的生理盐水。在整个实验期间,观察小鼠的一般状态,食量,     

不同剂量四氧嘧啶皮下注射对大鼠糖尿病模型稳定性的影响

目的:研究制备2型糖尿病模型大鼠皮下注射四氧嘧啶的最低剂量及其稳定性。方法:采用皮下注射不同剂量的四氧嘧啶,观察其制模成功率、死亡率及血糖稳定性来判断。结果:高、中剂量组大鼠成模型率100%,低剂量组成模率65%,高剂量组死亡率45%,中剂量组死亡率20%,低剂量组死亡率15.4%,从模型的稳定性看,高、中剂量组模型大鼠2周内血糖、尿糖基本保持高水平不变,低剂量组大鼠在1周内血糖、尿糖仍可保持高水平,但2周后有下降趋势。结论:从剂量及造模稳定性看,中剂量组(皮下注射四氧嘧啶120mg/100g)成模率高,死亡率低,模型稳定,为最佳皮下给药剂量。     

不同剂量四氧嘧啶皮下注射对大鼠糖尿病模型稳定性的影响

目的：研究制备Ⅱ型糖尿病模型大鼠皮下注射四氧嘧啶的最低剂量及其稳定性。方法：采用皮下注射不同剂量的四氧嘧啶，观察其制模成功率、死亡率及血糖稳定性。结果：高、中剂量组大鼠成模率为100％，低剂量组成模率为65％；高剂量组死亡率为45％，中剂量组死亡率为20％，低剂量组死亡率为15．4％，从模型的稳定性看，高、中剂量组模型大鼠2周内血糖、尿糖基本保持高水平不变，低剂量组大鼠在1周内血糖、尿糖仍可保持高水平，但2周后有下降趋势。结论：中剂量组（皮下注射四氧嘧啶120mg／100g体重）成模率高，死亡率低，模型稳定，为最佳皮下给药剂量。     

罗格列酮对糖尿病模型兔体质量、FPG及FFA等指标的影响

目的:研究罗格列酮(RH)对糖尿病模型兔体质量,空腹血糖(FPG)及游离脂肪酸(FFA)等的影响。方法:取18只兔随机均分为对照组、模型组、右旋糖酐组,后2组兔iv四氧嘧啶复制糖尿病模型,然后3组兔ig RH(0.5 mg/kg),其中右旋糖酐组兔给药同时iv右旋糖酐40葡萄糖注射液(5 ml/kg),每日1次,连续给药3周。检测给药前及给药后各组兔的体质量和血清中FPG、FFA、血管紧张素Ⅱ(AngⅡ)、NO水平。结果:与给药前比较,对照组兔给药后体质量增加,FFA、AngⅡ水平降低;模型组兔给药后FPG、FFA水平降低;右旋糖酐组兔给药后体质量降低,差异有统计学意义(P<0.01或P<0.05),其余指标差异无统计学意义(P>0.05)。其中,右旋糖酐组兔给药后FFA水平高于模型组,差异有统计学意义(P<0.01)。结论:罗格列酮可增加兔的体质量,其机制可能与降低FFA水平有关。     

钝顶螺旋藻多糖降血糖调血脂实验研究

目的 :观察螺旋藻多糖 (PSP)对四氧嘧啶 (ALX)性糖尿病大鼠血糖、血脂水平的影响。方法 :用ALX建立糖尿病大鼠模型 ,分别用PSP 0 .1、0 .2 g/kg及阳性对照药苯乙双胍 0 .350 g/kg灌胃治疗 ,正常对照组及糖尿病模型对照组则给等容积生理盐水。连续给药 1 4d后 ,分别测定各组大鼠血糖、血脂。结果 :PSP 0 .1、0 .2 g/kg能明显降低ALX所致糖尿病大鼠高血糖 ,与糖尿病模型对照组相比 ,P <0 .0 1 ;同时 ,相同剂量的PSP还能明显降低ALX性糖尿病大鼠血清总胆固醇、甘油三酯、低密度脂蛋白胆固醇 (P <0 .0 1 )。PSP 0 .2 g/kg还使糖尿病大鼠血清HDL C显著回升 (P <0 .0 5) ,而PSP 0 .1 g/kg对糖尿病大鼠血清HDL C则无明显影响 (P >0 .0 5)。 结论 :PSP能明显降低ALX性糖尿病大鼠高血糖及高血脂     

四氧嘧啶致大鼠糖尿病模型的比较

随着人口老龄化和人们生活水平的不断提高,生活节奏的不断加快,糖尿病的发病率呈逐年上升趋势。糖尿病对人体的危害仅次于癌症[1]。化学药物四氧嘧啶(Alloxan.,ALX)法是常用的一种经济有效的制作糖尿病模型的方法[2]而用于抗糖尿病药物的研究,ALX制作大鼠糖尿病模型受动物体重、禁食时间、给药剂量等各种因素的影响,文献报道用ALX制作大鼠糖尿病模型静脉给药优于腹腔给药,但对不同品系大鼠对ALX致糖尿病模型的影响未见报道[3].本实验选择常用的Wistar和SD2个不同品系大鼠对ALX致糖尿病模型的差异进行了比较研究。1材料与方法1.1动物…     

螺旋藻多糖对糖尿病小鼠抗氧化能力的影响

腹腔注射四氧嘧啶（ＡＬＸ）２００mg/kg建立糖尿病模型小鼠,并随机分为４组,分别用螺旋藻多糖（ＰＳＰ）１００mg/kg、２００mg/kg及阳性对照药优降糖２mg/kg灌胃给药,糖尿病模型对照组则给等容积生理盐水,连续１４d后,分别测定各组小鼠血糖、血清ＳＯＤ活性、ＭＤＡ含量及全血ＧＳＨ－Ｐx活性与ＧＳＨ含量。结果与糖尿病模型对照组相比,ＰＳＰ能使ＡＬＸ所致糖尿病小鼠血糖降低（Ｐ＜０.０１）;血清ＳＯＤ活性、全血ＧＳＨ－Ｐx活性及ＧＳＨ一显著回升（Ｐ＜０.０１）;血清ＭＤＡ含量明显下降（Ｐ＜０.０１）。结果表明ＰＳＰ能降低ＡＬＸ性糖尿病小鼠高血糖并显著增强其抗氧化能力。提示ＰＳＰ降血糖作用的机制可能与其增强糖尿病鼠抗氧化能力有关。     

Hypoglycaemic activity of dioscoretine from tubers of Dioscorea dumetorum in normal and alloxan diabetic rabbits

Dioscoretine isolated from the aqueous fraction of the methanol extract of Dioscorea dumetorum tubers when administered intra-peritoneally to normal and alloxan diabetic rabbits produces significant hypoglycaemic effects at a dose of 20 mg/kg. The fasting blood sugar in normoglycaemic rabbits was reduced from 112 mg/100 ml to 55 mg/100 ml after 4 hours. In alloxan diabetic rabbits, the blood sugar was lowered from 520 mg/100 ml to 286 mg/100 ml at the same time interval. The aqueous fraction of the methanol extract produced comparable effects at 100 mg/kg. The chloroform fraction of the same extract raised the fasting blood sugar of normal rabbits to 196 mg/100 ml after 6 h. The acute toxicity studies gave LD50 values of 1.4 g/kg for the aqueous fraction and 0.58 g/kg for dioscoretine when tested on mice. The hypoglycaemic effects were compared to those of tolbutamide.     

玉竹总皂苷降血糖作用实验研究

目的研究玉竹总皂苷（total saponins from Polygonatum odoratum,TSPO）对正常小鼠和四氧嘧啶高糖小鼠血糖的影响,并探讨其降血糖机制。方法测定TSPO对α-葡萄糖苷酶活性的体外抑制率;研究TSPO对正常小鼠和四氧嘧啶高糖小鼠空腹血糖和灌胃淀粉后血糖的影响。结果 TSPO能够显著性抑制α-葡萄糖苷酶的活性,抑制率为58%;TSPO对正常小鼠血糖没有明显影响,但使其糖耐量曲线趋于平缓;TSPO能够显著提高四氧嘧啶高糖小鼠的糖耐量,并显著降低其空腹血糖。结论 TSPO有α-葡萄糖苷酶抑制作用,对四氧嘧啶高糖小鼠有降血糖作用。     

Taurine ameliorate alloxan induced oxidative stress and intrinsic apoptotic pathway in the hepatic tissue of diabetic rats

Oxidative stress is associated with various diabetic complications and taurine plays an important role in ameliorating those difficulties. In the present study we, therefore, investigated whether taurine plays any beneficial role against diabetes induced liver dysfunction and if it does, what cellular mechanism it follows during protective action. Induction of diabetes by alloxan (ALX) (at a dose of 120 mg/kg body weight, i.p., once) reduced body weight and plasma insulin level, enhanced blood glucose and serum markers related to hepatic injury, accelerated ROS production, disturbed the intra-cellular antioxidant machineries and disintegrated hepatic cells near central vein. This pathophysiology leads to apoptotic cell death as evidenced from DNA fragmentation and TUNEL aasay. Studies on the mechanism of apoptosis showed that ALX accelerated the markers of mitochondrial dependent apoptotic pathway (enhanced cytochrome C release in cytosol from mitochondria, altered the expression of Bax, Bcl-2, Apaf-1, caspase-9, caspase-3). Treatment with taurine (1% w/v for three weeks) post-hyperglycemia, however, could restore all the alteration caused by ALX. Moreover, taurine activates hepatic PI3Kinase, Akt, hexokinase and augments the translocation of GLUT 2 to hepatic membrane in diabetic rats. Combining all, as a potential therapeutic, taurine may normalize the complications of diabetic liver injury.     

维药小枝玫瑰提取物对四氧嘧啶糖尿病小鼠血糖及糖耐量的影响

目的观察小枝玫瑰Branchlets Rosa rugosa Thunb.提取物对四氧嘧啶糖尿病小鼠血糖及糖耐量的影响。方法采用四氧嘧啶造模法建立糖尿病小鼠模型,将造模成功的小鼠分为8组,分别为模型组,小枝玫瑰水提物高、中、低剂量（3.70、1.85、0.93 g/kg）组,小枝玫瑰醇提物高、中、低剂量（2.75、1.37、0.70 g/kg）组和盐酸二甲双胍（阳性药,200 mg/kg）组,另取正常小鼠为对照组,造模成功3 d后开始给药,每天ig给药1次,共30 d。造模后0、10、20、28 d血糖试纸法测定空腹血糖;造模后30 d,进行葡萄糖耐量试验。结果各组小枝玫瑰提取物均能降低糖尿病小鼠血糖、改善其糖耐量,且呈一定量效关系,其中以醇提物高剂量效果最好,但不及阳性药盐酸二甲双胍。结论小枝玫瑰提取物可以降低糖尿病小鼠血糖,对糖尿病小鼠糖耐量有改善作用。     

Mechanism of action of a hypoglycemic principle isolated from fenugreek seeds

Mechanism of action of an orally active hypoglycemic principle isolated from water extract of seeds of Trigonella foenum graecum (fenugreek) was investigated in alloxan induced subdiabetic and overtly diabetic rabbits of different severities. The active principle was orally administered to the subdiabetic and mild diabetic rabbits (five in each group) at a dose of 50 mg/kg body weight for 15 days. The treatment produced significant attenuation of the glucose tolerance curve and improvement in the glucose induced insulin response, suggesting that the hypoglycemic effect may be mediated through stimulating insulin synthesis and/or secretion from the beta pancreatic cells of Langerhans. Prolonged administration of the same dose of the active principle for 30 days to the severely diabetic rabbits (n = 5) lowered fasting blood glucose significantly, but could elevate the fasting serum insulin level to a much lower extent, which suggests an extra-pancreatic mode of action for the active principle. The effect may also be by increasing the sensitivity of tissues to available insulin. The hypoglycemic effect was observed to be slow but sustained, without any risk of developing severe hypoglycemia.     

多次低剂量链脲佐菌素诱导大鼠糖尿病模型的方法学研究

目的分别探讨造模后不同时间点禁食、大鼠性别和多次低剂量链脲佐菌素(STZ)对大鼠血糖及糖尿病模型成模率的影响。方法分别一次性腹腔注射(ip)STZ 30 mg.kg-160、62、64 h后,于晚8时、10时、12时禁食,次日晨8时测大鼠空腹血糖,计算糖尿病(空腹血糖≥7.0 mmol.L-1)成模率;记录雌鼠和雄鼠一次性ip STZ 30 mg.kg-1后糖尿病的成模情况;首次分别ip STZ(20、25、30、40和50 mg.kg-1),不成模大鼠再次ip STZ(20 mg.kg-1),比较各组间糖尿病成模情况、血糖水平和6周内大鼠死亡情况。结果晚10时和12时禁食组糖尿病成模数(均为8只)较晚8时禁食组成模数(4只)增加1倍,成模大鼠血糖值进一步升高;雄鼠糖尿病成模数(7只)较雌鼠成模数(4只)增加将近1倍,成模大鼠血糖值进一步升高;首次分别腹腔注射STZ 25、30、40和50 mg.kg-1各组大鼠累计成模率明显高于首剂20 mg.kg-1组;首剂50 mg.kg-1组6周内成模大鼠死亡率明显高于首剂STZ 25和30 mg.kg-1组。结论测大鼠空腹血糖前于晚10～12时禁食优于晚8时禁食;采用雄鼠造模优于雌鼠;首剂采用STZ 25～30 mg.kg-1腹腔注射,未成模大鼠继续采用STZ 20mg.kg-1腹腔注射,糖尿病成模率高,死亡率低。     

Pharmaceutical and biopharmaceutical evaluation of extracts from different plant parts of indigenous origin for their hypoglycemic responses in rabbits

This study was designed to evaluate the hypoglycemic effects of different plant extracts in single and in combined formulation, in experimentally induced "diabetic rabbits". The extracts were obtained from seeds of Syzygium jambolana, fruits of Momordica charantia and leaves of Azadirachta indica. Treatment of diabetes with plant extracts was started at 8 days after alloxan injection. Rabbits were randomly divided into four groups, each group consisting of six rabbits. Each group of rabbits was given a dose of granules containing 200 mg/kg b.w. concentrated ethanolic extract of a plant while the fourth group was given a dose of granules consisting of combined extract of all three folk plants. Blood samples were drawn at 0, 2, 4, 8, 12, 24, 36, 48, 72 and 96 h. Serum glucose estimation was done by glucose oxidase kit method. Anti-diabetic effect was produced after 72 h in groups 1, 2 and 3 that were administered with a dose of granules of ethanolic extract of single plant but in group 4, treated with 200 mg/kg body weight of combined extract of all three plants, hypoglycemic effect was produced after 96 h. Hypoglycemic effects may be induced in rabbits by administration of extracts of various plant parts. The hypoglycemic effect produced by granules of single plant extract was more pronounced than antidiabetic effect produced by combining three extracts in a single formulation.     

黄连素合用二甲双胍对糖尿病小鼠血糖的影响

目的探讨黄连素合用二甲双胍（B-M合剂,2∶1）对四氧嘧啶致糖尿病小鼠的降糖作用。方法小鼠腹腔注射四氧嘧啶造成糖尿病模型,分为B-M合剂高、中、低剂量组（400、200、100 mg/kg）、模型组、正常组。每天观察并记录各组动物摄食、饮水及体重情况;分别灌胃给药7 d和14 d,各组称体重,采血测定空腹血糖值,给药14 d后进行糖耐量实验。结果模型组小鼠观察到多饮、多食、多尿的情况,伴有体重明显下降;B-M合剂各剂量组小鼠的多饮多食症状均有一定程度改善,与模型组比较差异均有统计学意义（P〈0.05）;B-M合剂各剂量组体重较模型组增加,中、低剂量组与模型组比较差异有统计学意义（P〈0.05）。B-M合剂各剂量组在给药7 d降低空腹血糖值至11.37-13.04 mmol/L,与模型组比较差异有统计学意义（P〈0.01）;给药14 d降低空腹血糖值至9.36-19.78 mmol/L,与模型组比较差异有统计学意义（P〈0.05或P〈0.01）。此外,B-M合剂高剂量组可延缓糖尿病小鼠的糖耐量曲线,中剂量组（AUC：33.76±3.10）和低剂量组（AUC：39.91±2.95）可明显改善糖尿病小鼠的糖耐量异常,改善血糖调节功能,与模型组（AUC：50.75±3.94）比较差异有统计学意义（P〈0.01）。结论黄连素合用二甲双胍有良好的降糖作用。