链脲佐菌素对大鼠肝微粒体LPO模型的影响

目的　研究链脲佐菌素对大鼠肝微粒体LPO模型的影响及其剂量效应关系。方法　以钙沉淀法提取二级雄性SD大鼠肝微粒体 ,分别建立CCl4 、CHP和Vc/Fe2 + 等激发的微粒体LPO反应模型。向三类反应模型中加入不同剂量的链脲佐菌素 ,并调节至终浓度 :0 3 ,0 6,0 9,1 2 ,1 5,1 8mg/ml,分别测定LPO反应产物MDA的生成量。结果　与对照组相比 ,各实验组MDA产量均显著增加 (P <0 .0 1) ,并且随着链脲佐菌素剂量的增高 ,MDA产量亦增加 ,呈现良好的剂量效应关系。在三类模型中MDA产量随不同剂量的链脲佐菌素变化趋势相一致。结论　链脲佐菌素能加重大鼠肝微粒体LPO模型的脂质过氧化损伤 ,并且具有剂量 -效应关系     

链脲佐菌素注射剂量对建立2型糖尿病大鼠模型的影响

目的探讨不同链脲佐菌素(STZ)注射剂量和方法对大鼠血糖值、血糖稳定性和胰岛损害的影响。方法75只SPF级6周龄雄性Wistar大鼠高脂高糖、饲养8周后,分别给予20、25、30mg/kg的STZ腹腔注射。造模后连续7周每周观察各组大鼠的体重、空腹血糖和餐后2h血糖。评价各组大鼠血糖变化和成模率。实验结束时测定血清胰岛素(INS)、甘油三酯(TG)、总胆固醇(TC)、高密度脂蛋白(HDL)、低密度脂蛋白(LDL)等。HE染色和胰岛素免疫组化观察胰岛细胞形态学特点。结果20mg/kg注射组成模率较低(30%);25mg/kg注射组成模率较高(73.3%),血糖中度升高并且稳定,胰岛结构完整,β细胞数量和细胞质内棕色颗粒有所减少;30mg/kg的STZ注射组血糖较高,死亡率较高,并且胰岛和β细胞数量极少,小胰岛多见,形状不规则,出现空泡样变性。结论高脂、高糖饲养8周后联合小剂量STZ25mg/kg能够造成更具有代表人类2型糖尿病病理生理特征的大鼠模型。     

链脲佐菌素诱导大鼠Ⅰ型糖尿病模型的效果

目的用链脲佐菌素(Streptozotocin STZ),诱导大鼠Ⅰ型糖尿病模型(The Model of TypeⅠDiabetes T1DM),观察模型的稳定性及肝脏的病理生理学变化。方法 SD大鼠随机分为正常对照组和模型组两组,每组10只。模型组一次性腹腔注射2%STZ(60 mg.kg-1),正常组腹腔注射等体积柠檬酸缓冲液。于药后1、2、3、4周观察大鼠空腹血糖值(Fasting Blood Glucose FBG)及一般情况。实验结束后测血清谷丙转氨酶(Alanine Transarninase SLT)、谷草转氨酶(Aspartate Aminotransferase AST),取大鼠肝组织HE染色观察肝组织形态学变化。结果成模大鼠血糖呈3个时相变化,1、2周血糖稳定(P0.05),3周血糖在一定范围内波动(P0.05),4周内血糖均维持在高水平范围。随着病程延长,模型组大鼠出现典型糖尿病症状,肝组织结构发生病理学改变,血清SLT、AST明显升高(P0.01),出现糖尿病性肝损伤。结论 60 mg.kg-1剂量的STZ诱导大鼠T1DM模型,成模率高,4周内血糖均维持在高水平范围。随着病程延长,大鼠出现糖尿病性肝损伤。     

链脲佐菌素稳定性对小鼠糖尿病模型的影响

目的观察链脲佐菌素的稳定性及其诱导的糖尿病模型的影响。方法采用25～30g昆明种小鼠，用pH4．5的柠檬酸缓冲液溶解链脲佐菌素小鼠腹腔注射（链脲佐菌素注射量为：150mg／kg），第6d检测血糖，观察配置好的链脲佐菌素溶液对不同时间成模率的影响。结果0h组的成膜率高。结论在造膜时应尽快完成腹腔注射。     

不同种属和禁食时间对链脲佐菌素诱导糖尿病模型的影响研究

目的观察不同种属和禁食时间对链脲佐菌素诱导的糖尿病模型的影响。方法采用昆明种、BALB/c、ICR、C57BL/J6四种雌性小鼠,溶解链脲佐菌素小鼠腹腔注射,观察种属对模型成模率的影响;采用25～30g昆明种小鼠,用pH4.5的柠檬酸缓冲液溶解链脲佐菌素小鼠腹腔注射（链脲佐菌素注射量为：150mg/kg）,第6d检测血糖,观察小鼠不同禁食时间对成模率的影响。结果与结论C57BL/J6小鼠造模成功率为93.3%,其次为昆明种和ICR86.7%,最低为BALB/c80.0%;禁食14h组的成模率高。     

高脂饲料喂养时间及链脲佐菌素剂量对实验型2型糖尿病大鼠造模的影响

目的采用高脂饲料联合链脲佐菌素(STZ)诱导方法建立糖尿病大鼠模型,探讨模型死亡率和成模率的影响因素。方法 8周龄雄性Wistar大鼠在高脂饲料喂养0周、4周、6周或8周后分别腹腔注射30mg/kg STZ;雄性Wistar大鼠在高脂饲料喂养四周后分别腹腔注射20、30或60 mg/kg STZ建立糖尿病模型,做糖耐量实验及胰岛素耐量实验,并检测血清指标,然后再以罗格列酮作为阳性药物进行验证。结果大鼠在高脂饲料喂养4周后,腹腔注射STZ 30 mg/kg处理后,糖尿病大鼠模型成模率分别为85%和80%,高于20 mg/kg STZ组;死亡率为零,显著低于60 mg/kg STZ组(75%);高脂饲料喂养4周后注射30 mg/kg STZ组死亡率最低,而高脂饲料喂养8周模型组死亡率最高达65%。成模大鼠血清甘油三酯、游离脂肪酸显著升高(P<0.05),空腹血清胰岛素未明显下降,并出现糖耐量异常和胰岛素抵抗;罗格列酮治疗4周后血糖、血清甘油三酯及游离脂肪酸显著降低(P<0.05)。结论高脂饲料喂养时间、STZ剂量及鼠龄是影响糖尿病大鼠模型成模率和死亡率的重要因素。     

链脲佐菌素致小鼠糖尿病模型影响条件的实验研究

随着人们生活水平的提高和社会人口老龄化，糖尿病的发病率急剧上升，其中多数为非胰岛素依赖型糖尿病（Non-insu-lin-dependent diabetesmellitus，NIDDM）。因此，预防NID-DM及延缓并发症的发生是本世纪预防医学工作的重要课题。建立相应的动物模型已成为人类研究糖尿病的重要和必需手段之一。链脲佐菌素（streptozocin，STZ）对一定种属胰岛8细胞有选择性破坏作用，进而使动物产生糖尿病。因其对组织毒性小，动物存活率高，成为目前国内外使用较多的制备糖尿病动物模型的方法之一，但有关影响模型形成的因素的报道较少。     

硒、锌对链脲佐菌素所致胰岛氧化损伤的保护作用

用离体培养的新生大鼠胰岛，观察链脲佐菌素（ＳＴＺ）对胰岛过氧化氢（Ｈ２Ｏ２）释放和葡萄糖刺激胰岛素分泌的影响以及硒、锌的保护作用。结果显示：０．５～４ｍｍｏｌ／ＬＳＴＺ增加胰岛Ｈ２Ｏ２释放和抑制胰岛素分泌，均呈剂量依赖关系，且两者有负相关关系。硒可明显减少ＳＴＺ诱导的Ｈ２Ｏ２释放，而锌则无该效应，但硒和锌均能明显减轻ＳＴＺ和外源性Ｈ２Ｏ２抑制胰岛素分泌的作用。结果表明：Ｈ２Ｏ２在ＳＴＺ所致胰岛损伤中起重要作用，硒和锌对ＳＴＺ所致胰岛氧化损伤具有一定的防护作用。     

不同溶剂在链脲佐菌素血糖模型的作用比较

[目的]为比较不同溶剂在链脲佐菌素血糖模型的作用. [方法]采用pH 4.5柠檬酸PBS(A组)、pH 5.5 Hanks(B组)、pH 7.0 Hanks(C组)、pH 7.0生理盐水(D组)4种溶剂,溶解链脲佐菌素小鼠腹腔注射,观察溶剂及其酸碱度对模型的影响. [结果]pH 4.5柠檬酸PBS造模成功率高达86.7%,pH 4.5柠檬酸PBS可以作为理想的溶剂. [结论]酸性溶液成模率高.     

小鼠腹腔注射链脲佐菌素高血糖模型实验观察

目的：本实验采用小鼠腹腔注射链脲佐菌素，对形成的高血糖模型进行实验观察。方法：以150mg／kg体重剂量腹腔注射链脲佐菌素生理盐水溶液，观察成模率、6d、30d、45d血糖、体重变化。结果：造模后6d模型复制成功率为83．3％，体重变化与造模后血糖高低有关。结论：以150mg／kg体重剂量，小鼠腹腔注射链脲佐菌素生理盐水溶液，通过45d的饲养观察，空腹血糖值10～25mmol／L之间小鼠可以作为成功高血糖模型。     

氨基胍和维生素C对糖尿病大鼠血脂的影响

目的观察氨基胍、维生素C对糖尿病大鼠的血脂的影响。方法利用链脲佐菌素腹腔注射法诱导建立1型糖尿病大鼠模型,将实验用50只SD大鼠随机分为正常对照组、糖尿病组、维生素C治疗组、氨基胍治疗组、维生素C和氨基胍联合治疗组。治疗16周。观察治疗期间及治疗后大鼠的一般状况、血糖(BS)、甘油三酯(TG)、胆固醇(TC)、低密度脂蛋白(LDL-C)、高密度脂蛋白(HDL-C)、糖化血红蛋白(HbA1 c)、糖化低密度脂蛋白(G-LDL)。结果造模4组大鼠均出现血脂异常;氨基胍、维生素C对血糖无影响,但能改善基本状况,维生素C能降低糖尿病大鼠的甘油三酯、胆固醇、低密度脂蛋白、糖化血红蛋白、糖化低密度脂蛋白,升高高密度脂蛋白;两种药物联合用药具有协同作用。结论氨基胍、维生素C无降糖作用,但维生素C具有确切的调节血脂作用,联合用药有协同作用。     

1,25-二羟维生素D3的免疫调节作用

1,25-二羟维生素D3[1,25-dihydroxyvitamin D3,1,25-(OH)2D3]是维生素D3的活性形式,是第二甾体类激素,它除了调节机体的钙和骨代谢外,还参与免疫系统的分化与调节.1,25-(OH)2D3是通过与它的特定受体--维生素D受体相互作用来实现它的大部分基因效应的,抗原呈递细胞和T细胞是它作用的靶细胞,它的作用主要是诱导产生基因耐受性树突细胞,抑制致病性T淋巴细胞,促进调节性T淋巴细胞的增生.1,25-(OH)2D3及其类似物已经在许多实验模型中被证明能够抑制自身免疫性疾病和移植排斥反应,这是一个复杂和丰富的研究领域,可能让我们发现一种新的治疗自身免疫性疾病和移植排斥反应的重要方法.     

1,25-二羟基维生素D3对原发性骨质疏松骨折愈合的影响

目的探讨1，25-二羟基维生素D3（1，25（OH）2D3）对原发性骨质疏松骨折愈合的影响。方法采用8月龄雌性新西兰兔，摘除双侧卵巢法建立Ⅰ型骨质疏松模型，随机分为假手术组（Sham）、单纯去卵巢组（OVX）、葡萄糖酸钙组（OC）和葡萄糖酸钙＋1，25（OH）2D3组（OCR）。采用3岁龄新西兰雌兔和4岁龄新西兰雄兔，作为Ⅱ型骨质疏松动物模型，随机分为空白对照组（Control）、葡萄糖酸钙组（Calcium）、葡萄糖酸钙＋1，25（OH）2D3组（CR）。所有实验动物行双侧桡骨骨折模型。OC组和Calcium组单纯给予葡萄糖酸钙，OCR组和CR组给予葡萄糖酸钙和1，25（OH）2D3。于给药后2、4、8周给各实验组拍骨折X线片，8周测定各实验组骨痂、腰椎的骨密度（BMD），对骨痂组织进行组织学观察。结果给药8周后，OCR组的X线评分、腰椎和骨痂骨密度均较OVX组和OC组显著升高（P〈0.05或P〈0.01）。CR组的X线评分、腰椎和骨痂骨密度均较Control组和Calcium组显著升高（P〈0.05或P〈0.01）。结论1，25（OH）2D3对Ⅰ型和Ⅱ型骨质疏松骨折愈合均有促进作用。     

1,25-二羟基维生素D3对原发性骨质疏松骨代谢的影响

目的探讨1，25-二羟基维生素D3[1，25（OH）2D3]对原发性骨质疏松骨代谢的影响。方法采用8月龄雌性新西兰兔，摘除双侧卵巢建立Ⅰ型骨质疏松模型，随机分为假手术组（Sham）、单纯去卵巢组（OVX）、葡萄糖酸钙组（OC）和葡萄糖酸钙＋1，25（OH）2D，组（OCR）。采用3岁龄新西兰雌兔和4岁龄新西兰雄兔，作为Ⅱ型骨质疏松动物模型，随机分为空白对照组（Control）、葡萄糖酸钙组（Calcium）、葡萄糖酸钙＋1，25（OH）2D3组（CR）。OC组和Calcium组单纯给予葡萄糖酸钙，OCR组和CR组给予葡萄糖酸钙和1，25（OH）2D3。给药8周后测定各实验组的骨代谢生化指标。结果给药8周后，在Ⅰ型骨质疏松模型中，OCR组的血钙、血磷、碱性磷酸酶（ALP）均较OVX组和OC组显著升高（P〈0．05或P〈0．01），OCR组的BGP、尿Ca／Cr较OVX组和OC组明显降低（P〈0．05或P〈0．01）。在Ⅱ型骨质疏松模型中，雌、雄性兔CR组的血钙、BGP、ALP均较Control组和Calcium组有显著性升高（P〈0．05或P〈0．01），尿Ca／Cr较其他两组明显下降（P〈0.05或P〈0．01）。结论1，25（OH）2D3对Ⅰ型骨质疏松症有降低骨转换，促进骨形成，抑制骨吸收的作用；对Ⅱ型骨质疏松症有提高骨转换，促进骨形成，抑制骨吸收的作用。     

Effects of green tea on serum paraoxonase/arylesterase activities in streptozotocin-induced diabetic rats

In recent years, green tea has become a subject of interest because of its beneficial effects on human health. The purpose of this study was to determine the effects of green tea on serum paraoxonase/arylesterase activities and lipoprotein oxidizability in streptozotocin-induced diabetic rats (65 mg/kg [intraperitoneal]). Green tea was given in tap water (2%) for 3 and 6 weeks to control (CGT-3w and CGT-6w) and diabetic (DGT-3w and DGT-6w) rats, and they were compared with the control and diabetic groups (D-3w and D-6w), respectively. Serum insulin level was significantly increased in the DGT-6w group; serum lipid and plasma and tissue malondialdehyde levels were reduced in the DGT-3w and DGT-6w groups. Oxidizability of apolipoprotein B–containing lipoprotein fraction was found to be significantly reduced in the DGT-6w group. Serum total antioxidant capacity showed a significant increase in the CGT-6w and DGT-6w groups. Paraoxonase activity was significantly reduced in the D-3w and D-6w groups and increased in the DGT-6w group. We conclude that green tea might have antihyperlipidemic and antioxidative effects and may slow the progression of atherogenesis by reducing oxidation of lipoproteins and preserving paraoxonase activity.     

Enhanced radiosensitivity in 1,25-dihydroxyvitamin D3 deficient mice

To investigate whether impaired osteogenesis resulting from vitamin D deficiency can influence hematopoiesis recovery after radiation, the 25-hydroxyvitamin D-1α-hydroxylase (1α-hydroxylase) gene knockout (KO) mice and wild type (WT) mice were subjected to different doses of gamma ray. The survival rates, peripheral blood cell counts and bone marrow cellularity were studied after irradiation (IR). The survival rates of the KO mice were significantly lower than that of WT mice after 6 or 8 Gy dose of radiation. The recovery of white blood cells in KO mice was significantly delayed compared with that in WT mice after radiation. The red blood cell number in WT mice was observed to increase more than that in KO mice at days 14 and 28 after radiation. The nadir platelet count in KO mice was nearly half of that in WT mice. Dramatically higher bone marrow cell numbers were found in WT mice compared with KO mice. Our findings demonstrate the enhanced radiosensitivity in 1,25-dihydroxyvitamin D3 (1,25-(OH)(2)D(3)) deficient mice.     

Therapeutic role of low-carbohydrate ketogenic diet in diabetes

IntroductionChanges in dietary habits influence the glycemic level. Preliminary studies using the low-carbohydrate ketogenic diet (LCKD) were found to be quite promising in controlling diabetes mellitus. Therefore, the objectives of this study are to investigate the therapeutic effects of LCKD in experimental diabetic rats following the administration of streptozotocin (STZ).Materials and methodsAdult rats were divided into three groups: normal diet, LCKD, and high-carbohydrate diet. Each group was subdivided into normal, sham, and diabetic groups. Diabetes was induced by a single intraperitoneal injection of STZ (55 mg/kg). Specific diets were given to each group of animals for a period of 8 wk and then the animals were sacrificed. The rats were monitored daily for food and water intake, whereas body weight, urine output, and blood glucose levels were monitored weekly. The histology of the islets of Langerhans was studied by histochemical methods.ResultsThe results showed that LCKD was effective in bringing blood glucose level close to normal (P < 0.01). Food and water intake and urine output were increased in all groups except the LCKD group (P < 0.01). The body weight was significantly reduced in all diabetic animals except in the LCKD group (P < 0.01). Histologic studies showed significant decrease in the islet size and number of β cells in all the diabetic groups.ConclusionThis study indicates that LCKD has a significant beneficial effect in ameliorating the diabetic state and helping to stabilize hyperglycemia.     

Modification of streptozotocin-induced diabetes by protective agents

Streptozotocin is a unique molecule, containing both a methylating agent and a deoxyglucose in its structure. This drug possesses anticancer as well as diabetogenic properties and injection into laboratory animals elicits a cytotoxic response especially evident in the β cells of the islets of Langerhans. The mechanism of action of streptozotocin is associated with a depletion of pancreatic NAD content. This depletion, however, can be prevented by several protective agents, some of which have nutritional importance. This review examines the diet-drug interaction and gives examples of how certain substances can potentiate the beneficial action of streptozotocin while protect against its adverse effects. Use of pharmacologic and nutritional substances in determination of reaction mechanisms is discussed.     

Vanadyl sulfate treatment improves oxidative stress and increases serum paraoxonase activity in streptozotocin-induced diabetic rats

Vanadyl sulfate (VS) may reduce oxidative stress related to its hypoglycemic and hypolipidemic effects in diabetes mellitus; besides, as a catalytic element, it may induce lipid peroxidation. Studies investigating effects of VS on the oxidative-antioxidative systems in diabetes yielded conflicting results, and this study was designed to investigate the effects of VS on the oxidative-antioxidative systems in streptozotocin-induced (65 mg/kg) diabetic rats. Vanadyl sulfate was administered in drinking water 0.75 mg/mL during 5 weeks after the induction of diabetes. Thirty-two male Wistar rats were randomly divided into four groups: control (C), control + vanadyl sulfate (C + VS), diabetes (D), and diabetes + vanadyl sulfate (D + VS). Vanadyl sulfate reduced the enhanced glucose, lipid, and tissue malondialdehyde levels and increased the reduced serum paraoxonase and arylesterase activity in the D + VS group. Plasma malondialdehyde level was significantly increased in the C + VS group, compared with the control group. Erythrocyte glutathione peroxidase activity was significantly higher in the C + VS and D + VS groups, compared with the C and the D groups, respectively.

The results of the present study suggest that (i) VS has antioxidative potential in streptozotocin-treated rats, and it might be used as a supportive therapeutic agent in uncontrolled diabetes; (ii) VS treatment might play a role in the improvement of serum paraoxonase activity and, thus, inhibit the progression of atherosclerosis; (iii) the prooxidant potential of the VS should be taken into account.