延长糖尿病模型大鼠生存期对糖尿病视网膜病变的影响

目的延长糖尿病模型大鼠生存期,动态观察糖尿病视网膜病变(DR)的形成和发展过程。方法雄性SD大鼠70只,随机分成对照组(20只)和模型组(50只),采用链脲佐菌素(STZ)60 mg/(kg.bw)体重腹腔1次注射造模,分别于69、、12月时处死取眼球,采用视网膜微血管消化铺片技术观察糖尿病视网膜病变的微血管形态学改变。结果糖尿病大鼠DR样病变随着病程的延长病变呈多样性改变,以12月DR出现的小动脉硬化尤为严重。结论糖尿病大鼠生存期的延长对糖尿病视网膜病变的研究有着积极的意义。     

不同剂量链脲菌素对恒河猴某些常规生理指标的影响

目的　研究链脲菌素 (STZ)对恒河猴摄食、饮水、排尿、体重、血糖及尿糖等生理指标的影响 ,为建立糖尿病动物模型积累资料。方法　通过静脉给 7只恒河猴注射不同剂量的STZ。结果　使用不同剂量STZ后 ,7只恒河猴均在不同时间、不同程度出现与人糖尿病相类似的“三多一少”症状 ,同时对糖尿病猴使用不同剂量胰岛素可使其症状减轻。尤其是中、高剂量组的动物症状较为明显 ,而低剂量组体重有一个短时间的增加后又迅速下降。实验组中血糖和尿糖均出现不同程度的升高 ,以中、高 2个剂量组的动物变化较大。结论　采用中、高剂量组的STZ可诱导类似人类糖尿病的急性动物模型 ,而使用胰岛素治疗或低剂量STZ可使该动物模型疾病病程延长 ,有利于进行其并发症的研究。     

小剂量多次注射链脲佐菌素建立糖尿病早期视网膜病变动物模型

目的多次小剂量注射链脲佐菌素(STZ)制作糖尿病(DM)早期大鼠视网膜病变(DR)动物模型。方法雄性SD大鼠75只,体重(180±15)g。随机分为对照组(CON组,n=30)和模型组(DM组,n=45)。DM组按30mg/kg体重腹腔注射3%的STZ,连续5 d。成模后每周测量体重、血糖等指标。分别在成模后第4、8、12周各组随机安乐死10只动物,对视网膜组织进行H.E染色、免疫组化、消化铺片及透射电镜超微结构观察。结果模型成立后第2周,动物表现出多食、多饮、多尿的糖尿病症状。与对照组比较,模型大鼠4周时仅见视网膜变薄,8周时视网膜内皮细胞增生,毛细血管基底膜增厚,内皮细胞指状突起,吞饮泡增多。12周时毛细血管膨大,毛细血管细胞凋亡,核固缩、深染。视网膜变薄,神经节细胞数量减少。视网膜周细胞线粒体肿胀,嵴脱落空泡样变。模型组大鼠视网膜GFAP阳性细胞主要分布在节细胞层和神经纤维层,呈条索状连续排列,阳性细胞数明显减少。结论小剂量多次注射STZ诱导的大鼠DR模型表现出人类早期视网膜病变相似的特征,可用于发病机理、药效学等方面的研究。     

不同剂量链尿佐菌素诱导2型糖尿病大鼠模型的研究

目的:探讨不同剂量链脲佐菌素(Streptozotocin,STZ)联合高糖高脂饮食对2型糖尿病大鼠模型建立的影响。方法:90只8周龄SD雄性大鼠随机平均分为六组:普通饲料喂养+缓冲液组、高糖高脂饲料喂养+缓冲液(H.E组)、高糖高脂饲料喂养+35mg/kg链尿佐菌素组(H.E+35 mg/kg STZ组)、高糖高脂饲料喂养+45 mg/kg链尿佐菌素组(H.E+45 mg/kg STZ组)、高糖高脂饲料喂养+55 mg/kg链尿佐菌素组(H.E+55 mg/kg STZ组)及高糖高脂饲料喂养+65 mg/kg链尿佐菌素组(H.E+65 mg/kg STZ组),高糖高脂饲料喂养4周后诱导胰岛素抵抗,继之腹腔注射STZ,建立2型糖尿病大鼠模型。检测体重、胰岛素、空腹血糖、血脂、胰岛素敏感指数(ISI)。结果:与常规饮食组相比,高糖高脂饮食各组大鼠出现空腹血浆胰岛素(FINS)、空腹血糖(FBG)、血清甘油三脂(TG)、总胆固醇(TC)、游离脂肪酸(FFA)显著升高(P0.01),ISI显著下降(P0.01)。不同剂量STZ注射,H.E+45 mg/kg STZ组成模率最高且无自愈现象。结论:通过STZ腹腔注射联合高糖高脂饮食可成功复制出实验性2型糖尿病动物模型,45 mg/kg为STZ理想注射剂量。     

链脲菌素诱发新生期大鼠糖尿病的量效关系及其胸腺淋巴细胞增殖活性的变化

目的　研究链脲菌素 (STZ)处理新生期大鼠后诱发成年发病糖尿病的量效关系及其胸腺淋巴细胞增殖活性的变化。方法　STZ分别以 2 0、40、6 0及 10 0mg kg ,ip ,给予Wistar新生期大鼠 ,于注射STZ后第 3天、第 7天、第 17天、第 42天观察体重、血糖、血浆胰岛素及胸腺淋巴细胞增殖反应的动态变化。结果　 10 0mg kg剂量组可于第 42天形成慢性糖尿病模型 ,血糖值 (16 8± 4 6 )mmol Lvs (5 8± 1 6 )mmol L ,P <0 0 0 1;血浆胰岛素水平(5 2± 1 2 )mIU Lvs(8 4± 1 6 )mIU L ,P <0 0 1) ,胸腺淋巴细胞增殖呈现升高、受抑制再恢复的变化过程。其他各剂量组 ,特别是 40mg kg虽无明显高血糖形成 ,但可使胸腺淋巴细胞增殖活性增强。结论　STZ(10 0mg kg,ip)处理新生期大鼠诱发糖尿病的最适剂量为 10 0mg kg ,诱发时间为 42d。诱发过程中伴有胸腺增殖活性的变化。     

链脲佐菌素诱导C57小鼠1型糖尿病模型的研究

目的:通过小剂量多次腹腔注射链脲佐菌素(STZ)诱导建立与人类1型糖尿病相似的C57小鼠糖尿病模型,研究建模剂量和成模率。方法:将32只C57小鼠随机分为正常对照组(A)和实验组(B)。实验组(B)可分为低、中、高剂量组(50 mg/kg、70mg/kg、90 mg/kg)(n=8)。两组都喂普通饲料1周后,B组连续5天腹腔注射不同剂量STZ,测定注射前、注射后1周、2周、3周、4周、5周的空腹血糖和体重,观察小鼠饮食、饮水和排尿情况。STZ注射第3周进行口服糖耐量实验(OGTT)。结果:给药前A、B组体重和血糖无显著差异,给药1周后,B组饮水量和进食量明显增加,体重减轻。C57小鼠用药2周后,中剂量组达到建模标准,成模率75%。各剂量组均出现了糖耐量异常。结论:诱导建立C57小鼠1型糖尿病模型方法是连续5日腹腔注注射STZ,适宜剂量为70 mg/kg。     

链脲佐菌素诱导树鼩2型糖尿病

链脲佐菌素(streptozotocin,STZ)是链球菌产生的天然化合物,对哺乳动物的胰岛B细胞有特异毒性,被广泛用于诱导1型和2型糖尿病。该研究通过多次小剂量注射STZ来建立树鼩2型糖尿病动物模型。24只树鼩被分为对照组以及60、70和80mg/kg剂量STZ诱导组。注射STZ后,成模树鼩出现明显的多饮、多食和多尿症状,平均体重未减轻,高血糖症状持续8～16周,尿糖显著阳性,肾功能及糖耐受明显受损,糖脂代谢紊乱,但未出现糖尿病乳酸中毒和高血糖高渗等并发症。该结果表明,多次小剂量STZ注射可诱导树鼩出现类似2型糖尿病症状和糖尿病肾脏损伤,且综合考虑STZ注射次数、成模率以及成模稳定性,两次注射80mg/kg剂量的STZ较适合用于创建树鼩2型糖尿病模型。     

外源性及内源性生长抑素对链佐霉素糖尿病小鼠血清胰岛素的作用

已经证明用链佐霉素(简称 STZ)可诱发小鼠产生低胰岛素糖尿病,本工作用外源性注射生长抑素(简称 SS)和用半胱胺特异性耗竭内源性 SS 的方法,观察 SS 对 STZ 糖尿病小鼠血清胰岛素的影响。在注射 STZ(60mg/kg,ip)前10min 分别皮下注射 1μg/kg,5μg/kg,10μg/kg 的 SS 可预防 STZ 诱发的血清低胰岛素作用,并呈剂量-效应关系。注射半胱胺(300mg/kg,SC)24h 后再连续5d 皮下注射半量半胱胺维持,胰腺组织匀浆中的 SS 含量经放免测定鉴定已基本被耗竭。在实验的第7,9,11,16d 胰腺 SS 含量仍然维持在比对照组为低的水平,给这种小鼠注射 STZ,其血清胰岛素降低程度比仅接受 STZ 小鼠的大,此外,给耗竭胰腺内 SS的小鼠注射不足以引起高血糖的 STZ 也引起了血糖大大升高。以上结果表明,不仅外源性 SS有预防链佐霉素诱发的小鼠低血清胰岛素发生的作用,胰腺组织中的内源性 SS 也可能是一个对胰岛 B 细胞起保护作用的因素。     

不同剂量链脲佐菌素腹腔注射制备大鼠糖尿病心肌病模型的病理学观察

建立糖尿病性心肌病（DCM）大鼠模型,观察不同剂量链脲佐菌素（STZ）单次腹腔注射后大鼠心肌和胰腺的病理学变化。用STZ 50 mg/kg、55 mg/kg、60 mg/kg 3种剂量单次腹腔注射,制备糖尿病大鼠模型;以柠檬酸三钠-柠檬酸缓冲液腹腔注射,作为对照。72 h后,测空腹血糖及做口服葡萄糖耐量实验（OGTT）;3周后,HE染色观察各组大鼠胰腺和心肌形态学变化,Masson三色染色观察心肌纤维化改变。OGTT和空腹血糖显示3组存活大鼠糖尿病均成模;3周末,50 mg/kg和55 mg/kg剂量死亡率为25%;60 mg/kg剂量高,达到75%;HE染色显示55 mg/kg剂量组大鼠胰岛明显萎缩,轮廓不清晰,胰岛细胞数量少,心肌细胞肥大、排列紊乱,细胞间隙增大,并有炎症细胞浸润;50 mg/kg组胰岛和心肌也有变化,但无55 mg/kg组明显。心肌Masson染色显示55 mg/kg组心肌内胶原组织明显增多,排列紊乱,分布不均。55 mg/kg剂量的STZ单次注射大鼠腹腔,造模3周可以建立较明显的DCM模型,可为DCM的组织病理学和实验研究提供一个较好的动物模型。     

乌蕨醇提取物对1型糖尿病大鼠的降血糖作用及其机制初探北大核心CSCD

为探讨乌蕨醇提取物对1型糖尿病大鼠的降血糖作用及其机制,本研究以链脲佐菌素(STZ)腹腔注射诱导建立1型糖尿病大鼠模型,并将大鼠分为空白对照组、1型糖尿病模型组、乌蕨醇提取物低剂量组(30 mg/kg)和高剂量组(60 mg/kg)。分别用生理盐水及乌蕨醇提取物每天灌胃1次,连续28 d,灌胃容积为20 m L/kg。结果证明,乌蕨醇提取物可减缓STZ致1型糖尿病大鼠体重的负增长,降低空腹血糖水平(P <0. 05);升高胰岛素及葡萄糖激酶(GCK)含量;降低醛糖还原酶(AR)含量(P <0. 05)。同时,胰腺组织HE染色结果显示:乌蕨提取物高、低剂量组糖尿病大鼠的胰岛数目较1型糖尿病模型组显著增多,胰岛及外分泌腺萎缩均有不同程度减轻。提示乌蕨提取物可显著降低STZ致1型糖尿病模型大鼠空腹血糖水平,其降糖作用可能与升高糖尿病大鼠血清葡萄糖激酶含量和降低AR含量、改善糖尿病大鼠胰岛损伤、促进胰岛β细胞分泌胰岛素有关。     

STZ诱导恒河猴糖尿病动物模型的建立

目的复制稳定的链脲佐菌素诱导糖尿病恒河猴动物模型。方法健康恒河猴5只,小剂量（30mg/kg）多次静脉注射链脲佐菌素,分别在注射后2、3个月进行葡萄糖耐量实验并连续观察血糖、胰岛素、C肽的变化。连续观察12个月。结果随着时间推移,动物出现典型的糖尿病症状。3只动物的血糖静脉注射1次后持续10周稳定,另外2只分别进行了第2、3次注射。动物血糖在12个月内平稳上升、胰岛素、C肽分泌持续下降。2个月时葡萄糖耐量减低明显（P〈0.01）。结论小剂量多次注射STZ后恒河猴可出现持续、稳定的糖尿病表现,可作为相关研究的动物模型。     

Antihypertensive treatment in spontaneously hypertensive rats with streptozotocin-induced diabetes mellitus

Recent clinical reports have suggested that hypertension accelerates the progress of diabetic nephropathy and retinopathy, whereas antihypertensive treatments may retard them. Thus, the effect of antihypertensive treatment in diabetes mellitus with hypertension was evaluated in rats. A model of diabetes mellitus with hypertension has been developed in spontaneously hypertensive (SHR) rats by unilateral nephrectomy and streptozotocin (STZ, 30 mg/kg, i.v. treatment). The rats were treated with four antihypertensive drugs orally for 12 weeks thereafter. STZ treatment induced chronic hypeglycaemia (300-400 mg/dl), decreased body weight and heart rate, and caused vascular changes of ophthalmic fundi and cataracta. The kidney of these rats showed proliferative changes such as periarteritis nodosa, hyperplasia, or fibronecrosis of the arterioles, exudative changes, mesangial proliferation, or thickening of the basement membrane of the glomeruli. Enalapril (10 mg/kg per day) and remipril (Hoe 498) (1 mg/kg per day), converting enzyme inhibitors, or arotinolol (20 mg/kg per day), a beta-adrenoceptor blocking drug, decreased blood pressure, prevented the development of renal and ocular lesions, and tended to increase creatinine clearance. Nisoldipine (3 mg/kg per day), a calcium-entry blocking drug, tended to decrease blood glucose, and prevented the decrease of body weight and development of ocular lesions. In conclusion, antihypertensive treatments were effective in preventing the progress of diabetic retinopathy and nephropathy, and renal insufficiency in this animal model.     

链脲佐菌素诱导SD和Wistar大鼠糖尿病模型的影响因素

目的通过注射链脲佐菌素（STZ）制作SD和Wistar大鼠糖尿病模型,观察大鼠品系、给药剂量、给药次数对大鼠成模率、死亡率的影响,同时研究利用口服葡萄糖耐量试验（OGTT）判断大鼠糖尿病成模率的意义。方法设置共同的正常对照组,①Wistar大鼠随机分为中剂量组（55 mg/kg）和高剂量组（65 mg/kg）;②SD大鼠一次性腹腔注射STZ（55 mg/kg）,与①中的Wistar大鼠作对比;③SD大鼠随机分为一次给药组和两次给药组,注射剂量均为55 mg/kg,观察期间进行OGTT。结果①Wistar大鼠成模率和死亡率均高于SD大鼠;②采用SD大鼠、中剂量给药和两次给药的方式可提高成模率,并降低死亡率;③在有明确胰岛病理改变的模型组大鼠,其OGTT异常阳性率显著高于空腹血糖异常阳性率。结论用STZ诱导糖尿病模型是一种稳定可靠的方法。Wistar大鼠成模率和死亡率均高于SD大鼠;选用中剂量给药及两次给药的方式可提高SD大鼠成模率,并降低死亡率,维持时间较长。在动物实验中OGTT比空腹血糖监测更有诊断意义,不易造成漏诊。     

Pomegranate (Punica granatum L.) flower improves learning and memory performances impaired by diabetes mellitus in rats

Oxidative stress induced by diabetes mellitus leads to damages in the brain, as a consequence of which cognitive functions is impaired. Therefore, for the treatment of diabetes mellitus, in addition to antidiabetics, antioxidants are used to cope with oxidative stress. The antioxidant ability of pomegranate flowers (PGF) to cope with the oxidative stress was investigated. Rats were divided into five groups with 12 animals in each group as given below: control, diabetes (STZ), STZ + the PGF I (300 mg/kg/day), STZ + PGF II (400 mg/kg/day) and STZ + PGF III (500 mg/kg/day).The findings from Morris water maze and probe tests showed that the animals in STZ group had impairments in learning and memory performances compared to the control group. Supplementation of PGF led to improvements in learning and memory performances of diabetic rats.While lipid peroxidation (LPO) was increased (P<0.001), glutathione (GSH) content was decreased (P<0.001) in hippocampal tissue of STZ-induced diabetic rats when compared with control values. Supplementation of PGF restored the levels of LPO and GSH towards their control values. Daily PGF supplementation to diabetic rats reduced the increase in glial-fibrilar acidic protein (GFAP) contents induced by diabetes in the hippocampus, which was significant in STZ + PGF III in comparison to STZ group (p<0.05).In conclusion, these observations suggest that PGF supplementation decreases oxidative stress and ameliorates impairment in learning and memory performances in diabetic rats. Therefore, we suggest that PGF supplementation may be clinically useful in treating neuronal deficit in diabetic patients.     

恒河猴糖尿病动物模型血清及组织中细胞因子的变化

目的探讨恒河猴糖尿模型病细胞因子的水平和变化规律。方法健康恒河猴5只,小剂量(30mg/kg)多次静脉注射链脲佐菌素(STZ),血糖稳定后3、9、12和19个月检测血清中白细胞介素-6(IL-6)、白细胞介素-10(IL-10)、肿瘤坏死因子-α(TNF-α)的含量。安乐濒死状态的动物,取胰腺、肝脏、肾脏制成石蜡切片,用免疫组化染色法显示组织中IL-6、IL-10、TNF-α的表达,并对结果进行图像分析和统计学处理。结果造模后9个月动物血清中IL-10浓度显著降低(P<0.01)。IL-6、TNF-α水平在采样的各个时间点均显著高于造模前(P<0.01)。胰腺组织中IL-6中等强度着色,对照组弱阳性表达(P<0.05)。对照组IL-10强阳性表达,模型组弱阳性(P<0.01)。模型组TNF-α中等强度表达,对照组弱阳性(P<0.05)。模型组肝脏组织TNF-α中等阳性表达,对照组弱阳性(P<0.05)。结论小剂量多次注射STZ后恒河猴细胞因子的含量及变化与临床类似,可作为相关研究的动物模型。     

Streptozotocin-induced diabetes mellitus in cynomolgus monkeys: changes in carbohydrate metabolism, skin glycation, and pancreatic islets

Chronic hyperglycemia has been implicated in a number of diabetes mellitus-related conditions in the human population, including retinopathy, neuropathy, nephropathy, and vasculopathy. However, it has been difficult to evaluate the effect of long-term hyperglycemia in a research setting because of the disease's slow progression. In this study, we used streptozotocin (30 mg/kg of body weight, intravenously) to induce a state of chronic hyperglycemia in eight cynomolgus monkeys, and compared these monkeys with a matched control group (n = 8). Seven of eight monkeys with streptozotocin-induced diabetes required insulin therapy to avoid ketosis. After disease induction, all diabetic monkeys had significantly higher preprandial plasma glucose and glycated hemoglobin values, compared with their baseline values or values for control monkeys. Diabetic monkeys also had abnormal responses to an intravenous glucose tolerance test. Consistent with the chronic hyperglycemic state and formation of advanced glycation end products, diabetic monkeys had a significant increase in skin fluorescence over the course of the 6-month study. Plasma triglyceride and cholesterol concentrations increased, but not significantly so, in the diabetic monkeys after disease induction and were not significantly different from concentrations in control monkeys. Six months after disease induction, monkeys were necropsied, and immunohistochemical staining for insulin in the pancreatic islets indicated that diabetic monkeys had a significantly decreased amount of staining for the hormone. The percentage of islet insulin staining was significantly correlated with physiologic responses to the postinduction intravenous glucose tolerance test in all monkeys. Because cynomolgus monkeys are well-characterized models of atherosclerosis, this model may be useful for determining mechanisms whereby diabetes mellitus increases cardiovascular disease.     

Protective role of zinc in liver damage in experimental diabetes demonstrated via different biochemical parameters

Diabetes mellitus is a serious worldwide metabolic disease, which is accompanied by hyperglycaemia and affects all organs and body system. Zinc (Zn) is a basic cofactor for many enzymes, which also plays an important role in stabilising the structure of insulin. Liver is the most important target organ after pancreas in diabetic complications. In this study, we aimed to investigate the protective role of Zn in liver damage in streptozotocin (STZ)‐induced diabetes mellitus. There are four experimental groups of female Swiss albino rats: group I: control; group II: control + ZnSO₄; group III: STZ‐induced diabetic animals and group IV: STZ‐diabetic + ZnSO₄. To induce diabetes, STZ was injected intraperitoneally (65 mg/kg). ZnSO₄ (100 mg/kg) was given daily to groups II and IV by gavage for 60 days. At the end of the experiment, rats were killed under anaesthesia and liver tissues were collected. In the diabetic group, hexose, hexosamine, fucose, sialic acid levels, arginase, adenosine deaminase, tissue factor activities and protein carbonyl levels increased, whereas catalase, superoxide dismutase, glutathione‐S‐transferase, glutathione peroxidase, glutathione reductase and Na⁺/K⁺‐ATPase activities decreased. The administration of Zn to the diabetic group reversed all the negative effects/activities. According to these results, we can suggest that Zn has a protective role against STZ‐induced diabetic liver damage.     

Parameters of systemic hemodynamics in conscious rats with acute streptozotocin diabetes]

The effect of acute streptozotocin-induced diabetes mellitus on the systemic hemodynamic parameters was studied in conscious rats by thermodilution technique. Male Wistar rats were made diabetic with a single intravenous injection of streptozotocin (STZ, 50 mg/kg). The most important finding of this work was the elucidation of the systemic vasodilation and increased cardiac index one day after STZ injection. Such alteration in hemodynamic parameters could result in the increased blood flow and capillary hypertension in some vascular beds and, therefore, be considered as a pathogenic factor in the development of diabetic microangiopathy.