实验性糖尿病小鼠的血清氨基酸代谢谱

目的通过测定2型糖尿病小鼠血清氨基酸代谢谱的变化,探讨代谢轮廓分析结合模式识别技术在糖尿病动物模型中的应用。方法 SPF级雄KM小鼠高脂饲料喂养4周后,腹腔注射链脲菌素(streptozotocin,STZ)建立2型糖尿病模型,动态监测空腹血糖(FBG)变化,分别于造模后第4周处死,收集小鼠血清,检测甘油三酯(TG)、总胆固醇(TC)、高密度脂蛋白(HDL)、低密度脂蛋白(LDL)水平。采用高效液相色谱(HPLC)柱前衍生方法检测小鼠血清中氨基酸代谢谱的变化。结果 2型糖尿病小鼠FBG、TG、TC明显升高,差异均有显著性。利用代谢轮廓分析可以对模型组大鼠代谢谱与对照组完全区分。结论小鼠成模后体内氨基酸发生了明显变化。从差异变量中鉴定出4个氨基酸对组间贡献较大(精氨酸、苯丙氨酸、赖氨酸、牛磺酸)。氨基酸的代谢轮廓分析结合模式识别技术可以在一定程度上反映2型糖尿病小鼠的代谢变化。     

2型糖尿病大鼠主动脉硬化模型的构建

目的:建立自发2型糖尿病大鼠主动脉硬化动物模型.方法:用2型糖尿病大鼠主动脉硬化动物模型,44只GK大鼠随机分为正常GK对照组、建模组,每组22只,正常Wistar大鼠组22只.期间观察大鼠血糖、尿糖及一般情况变化,8周后,测定各组动物空腹血糖、总胆固醇(total cholesterol,TC)、甘油三酯(triglycerides,TG)、低密度脂蛋白胆固醇(low density lipoprotein choleste rol,LDL-C),同时光学显微镜观察主动脉结构.结果:模型组大鼠的总胆固醇、甘油三酯、低密度脂蛋白胆固醇明显升高,出现主动脉肥大,病理显示明显的主动脉及动脉内膜病变.结论:通过高脂、一氧化氮合成酶抑制剂,可成功构建自发2型糖尿痛大鼠主动脉病变,用作2型糖尿病大鼠大血管病变研究的动物模型.     

青春双歧杆菌对2型糖尿病模型大鼠肠道菌群和脂质代谢的影响

目的通过观察青春双歧杆菌对2型糖尿病模型大鼠肠道菌群的变化,和血清中总胆固醇（TC）、甘油三酯（TG）、高密度脂蛋白（HDL-C）、超氧化物歧化酶（SOD）和丙二醛（MDA）的水平,探讨青春双歧杆菌对2型糖尿病模型大鼠肠道功能和脂质代谢的影响。方法采用青春双歧杆菌灌胃2型糖尿病模型大鼠,取粪便检查正常菌群,取血和脏器检测TC、TG、HDL-C、SOD和MDA含量。结果青春双歧杆菌导致肠道内双歧杆菌、乳杆菌的数量增加,而肠杆菌、肠球菌数量下降;TC、TG和MDA水平下降,而HDL-C和SOD水平升高。结论青春双歧杆菌具有改善2型糖尿病模型大鼠肠道功能和降血脂作用,与二甲双胍联合应用效果更佳。     

归芪多糖-2A对2型糖尿病大鼠肾保护作用的研究

本文研究了归芪多糖-2A(AAP-2A)对2型糖尿病大鼠肾组织的保护作用。采用高糖高脂饲料与低剂量链脲佐菌素(35 mg/kg)联合诱导的方法建立2型糖尿病大鼠模型,以不同剂量(1、0.5 g/kg/d)的AAP-2A连续灌胃42 d,检测糖尿病大鼠血糖、血脂、胰岛素、肾功能、肾组织氧化应激以及炎症因子等相关指标的变化。结果显示,AAP-2A可不同程度的降低糖尿病大鼠血清FBG、TC、TG、BUN和SCr的水平,提高胰岛素敏感指数(ISI),增强糖尿病大鼠肾脏SOD与GSH-PX活性,降低MDA、NF-κB与ICAM-1的含量。上述结果表明,AAP-2A可有效降低2型糖尿病大鼠的血糖水平,纠正脂代谢紊乱,增强肾组织的抗氧化能力,降低其炎症因子,起到保护糖尿病大鼠肾功能的作用。     

镁补充对2 型糖尿病大鼠糖脂代谢的影响

目的:研究镁补充对2型糖尿病大鼠糖脂代谢的影响。方法:将用高脂饮食联合链脲佐菌素(STZ)方法诱发的2型糖尿病大鼠随机分为四个组,糖尿病对照组喂饲高脂饲料,高、中、低剂量组在高脂饲料中分别加入2000、1000、200 mg/kg的镁(以镁离子计)。自由饮食喂养四周,处死动物。用放射免疫法测血清胰岛素(Ins)水平、用葡萄糖氧化酶法测空腹血浆葡萄糖(fasting plasmaglucose,FPG),并计算胰岛素敏感指数(insulin sensitivity index,ISI)。比色法检测糖化血红蛋白(glycosylated hemoglobin,HbA1c)。用全自动生化分析仪测高密度脂蛋白胆固醇(high-density lipoprotein cholesterol,HDLC)、甘油三酯(triglyceride,TG)、总胆固醇(total cholesterol,TC)。结果:高剂量组的空腹血糖、空腹血清、糖化血红蛋白、甘油三酯、总胆固醇水平均较糖尿病对照组显著性降低(P<0.05),而高密度脂蛋白胆固醇、胰岛素敏感指数较糖尿病对照组显著性升高(P<0.05)。结论:镁补充可以提高2型糖尿病大鼠胰岛素敏感性,改善糖尿病大鼠的糖脂代谢情况。     

高脂喂养合并小剂量链脲佐菌素建立2型糖尿病大鼠模型

目的 观察不同配方的高脂饲料,以及不同周龄的大鼠对于该模型的造模成功率和模型病变特点的影响.方法 将26只3周龄SD大鼠分为正常一组(N1组)、模型一组(M1组)和模型二组(M2组);26只5周龄SD大鼠分为正常二组(N2组)、模型三组(M3组)和模型四组(M4组).M1组和M3组给予高脂饲料配方一喂养,M2组和M4组给予高脂饲料配方二喂养.4周后,各模型组大鼠腹腔注射STZ溶液35 mg/kg.连续观察大鼠的空腹血糖(FBG)、空腹胰岛素(FIN)、总胆固醇(TG)、甘油三酯(TC)水平.结果 5周龄SD大鼠的FBG水平在注射STZ后两周即可达到稳定状态,并维持在较高的水平;高脂饲料配方二使大鼠的进食量和体重增加明显,并且成功诱导出胰岛素抵抗( insulin resistance,IR).结论 选取5周龄SD大鼠作为模型动物,并给予配方二高脂饲料喂养,所建立的大鼠模型具备2型糖尿病的主要特征,是值得推广的2型糖尿病动物模型.     

栀子水提取物对实验性2型糖尿病大鼠血糖及同型半胱氨酸水平的影响

观察栀子提取物对实验性2型糖尿病大鼠血糖、血脂及同型半胱氨酸水平的影响.采用Wistar雄性大鼠70只,随机抽取10只作为正常对照组,喂以普通维持饲料,其余60只高糖高脂饲料喂养4周后,ip链脲佐菌素(STZ)30 mg/kg建立2型糖尿病模型,7d后选取成模大鼠50只随机分为模型对照组(生理盐水)、盐酸二甲双胍对照组、栀子提取物低、中、高剂量组(0.2、0.4、0.6 g/kg),每组10只.连续ig给药4周后,观察各组大鼠血糖、血脂及同型半胱氨酸水平等变化.栀子提取物ig能降低糖尿病大鼠的血糖、甘油三酯(TG)、胆固醇(TC)、低密度脂蛋白(LDLC),同时能升高高密度脂蛋白(HDLC),降低同型半胱氨酸水平.     

瑞舒伐他汀对糖尿病大鼠早期动脉粥样硬化形成的影响

目的:观察他汀类调脂药物瑞舒伐他汀(Rosuvastatin)对2型糖尿病(type2diabetesmellitus,T2DM)大鼠早期动脉粥样硬化形成的影响,并探讨其可能的机制。方法:将45只雄性SD大鼠随机分为正常对照组(NC组)、2型糖尿病组(DM组)、2型糖尿病瑞舒伐他汀治疗组(DR组),每组15只。以喂高糖高脂饮食方法建立SD大鼠糖尿病模型,DM组、DR组给予高糖高脂饮食1个月后腹腔注射25mg/kg链脲佐菌素;NC组给予普通饮食,注射枸橼酸缓冲液作为对照。在此基础上,DR组给予瑞舒伐他汀5mg/(kg.d)灌胃,NC组、DM组给予生理盐水灌胃。16周后测定各组大鼠总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)水平与稳态血糖(BG)、稳态胰岛素(PGI)浓度,用免疫组化法检测主动脉血管壁白细胞分化抗原40(clusterofdifferentiation 40,CD40)及基质金属蛋白酶-2(MMP-2)、激活蛋白-1(activator protein-1,AP-1)的表达水平。结果:DM组、DR组TC、TG、LDL-C与BG水平较NC组均显著升高(F=33.71~426....     

基于肠道菌群和短链脂肪酸代谢探讨不同饮食条件下高脂血症大鼠发病机制

目的 本研究拟对比两种不同高脂饮食方式诱导的高脂血症大鼠肠道菌群变化与短链脂肪酸代谢特征,以宿主-肠道菌群-代谢角度探讨高脂血症可能的微观机制。方法 SPF级SD大鼠分为：正常饮食组(CG组):饲喂大鼠维持饲料;高脂饮食组(HFD1组):每天足量饲喂高脂饲料;限饲高脂饮食组(HFD2组):每天限量饲喂高脂饲料80 g,不限量饲喂维持饲料。8周后检测血清总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)和高密度脂蛋白胆固醇(HDL-C)水平;苏木精-伊红(HE)染色观察大鼠肝组织和肾周脂肪病理学变化;取结肠内容物进行16S rDNA高通量测序,观察肠道菌群结构与功能的变化,并检测结肠内容物中短链脂肪酸的含量。结果 与CG组相比,HFD1组和HFD2组大鼠摄食量下降,体重升高;血清中TC、TG、LDL-C均显著升高;肝组织发生明显脂肪变性,肾周脂肪出现炎性病变;高脂干预后大鼠肠道菌群相对丰度显著变化,其中乳杆菌属相对丰度明显降低,菌群结构和功能变化明显,总短链脂肪酸、乙酸、丁酸、异丁酸下降显著。结论 两种高脂饮食方式均能引起大鼠高脂血症,且发病机制基本一致,均与脂质代谢以...     

链尿佐菌素加高糖高脂饮食复制大鼠2型糖尿病模型

目的链尿佐菌素加高糖高脂饮食诱导大鼠2型糖尿病模型的建立。方法SD雄性大鼠高糖高脂饲料喂养3周后,采血检测空腹血糖及血清胰岛素,按25mg/g体重剂量一次性腹腔内注射链尿佐菌素,3d后,行糖耐量实验,对糖耐量异常大鼠继续喂以高糖高脂饲料,在第2、第4周再两次采血检测糖尿病鼠空腹血糖及血清胰岛素。结果与对照组比较,高糖高脂喂养大鼠血清胰岛素明显上升（P〈0.01）,但血糖无变化（P〉0.05）,糖尿病鼠血糖及血清胰岛素均显著的高于对照组（P〈0.01）。结论高糖高脂喂养能致大鼠明显的高胰岛素血症,辅以小剂量一次性注射链尿佐菌素而造成的糖耐量异常,可成功复制出2型糖尿病大鼠模型。     

骨形态发生蛋白-7及抑制性Smads在糖尿病肾病发生发展中的表达变化

本文采用免疫组化、Western blot及荧光实时定量PCR方法,动态观察链脲佐菌素（streptozocin,STZ）诱导的大鼠糖尿病肾病（diabetic nephropathy,DN）发生早期肾脏骨形态发生蛋白-7（bone morphogenetic protein-7,BMP-7）、Smad6、Smad7蛋白及mRNA表达。结果显示,在正常及DN大鼠肾小管均有BMP-7、Smad6、Smad7蛋白表达,以胞浆表达为主。DN大鼠BMP-7、Smad6蛋白表达较正常大鼠明显增多（P〈0．05）,且BMP-7的mRNA表达呈先增加后降低的状态;而Smad7蛋白和mRNA的表达均呈先增加后降低的状态。转化生长因子-β1（transforming growth factor-β1,TGF-β1）及Ⅰ型胶原（collagen typeⅠ,COL-Ⅰ）mRNA在DN大鼠肾脏表达较正常大鼠明显增多（P〈0．05）,且随着糖尿病进展有逐渐增加的趋势。结果提示,作为TGF-β超家族信号分子的一员,BMP-7信号及抑制性Smad通路在DN肾纤维化发生早期可能起重要的反馈性抑制作用。     

链脲佐菌素制备糖尿病大鼠模型探讨

目的探讨链脲佐菌素(STZ)配合不同饮食建立糖尿病模型的方法,并对模型大鼠学习记忆能力进行考察,为糖尿病的深入研究及药物开发提供可靠的模型。方法雄性SD大鼠70只,随机分为7组,分别为空白对照组(Ⅰ);高糖高脂膳食组(Ⅱ);0周STZ(30 mg/kg)+高糖高脂膳食组(Ⅲ);0周STZ(30 mg/kg)+常规膳食组(Ⅳ);6周STZ(20 mg/kg)+高糖高脂膳食组(Ⅴ);6周STZ(25 mg/kg)+高糖高脂膳食组(Ⅵ);6周STZ(30 mg/kg)+高糖高脂膳食组(Ⅶ)。采用尾静脉注射STZ配合不同饮食制备糖尿病模型,动态监测模型大鼠血糖的变化,生化方法检测大鼠血脂的改变,放免法检测模型大鼠血清胰岛素、胰高血糖素。Morris水迷宫检测不同造模型条件对大鼠空间学习记忆能力的影响。结果与对照组比较,Ⅲ组大鼠于注射72 h后血糖升高明显(P<0.01),至注射第2周血糖升高达顶点(P<0.01),以后逐渐降低,至观察第10周,血糖维持在15 mmol/L(P<0.05)。IV组大鼠于注射72 h后血糖升高,以后迅速降低,至观察第10周,血糖降低至正常水平。Ⅴ、Ⅵ、Ⅶ组大鼠于注射72 h后显著升高,此后呈波浪式变化;随着注射剂量增加,降低程度减慢。高糖高脂饲料喂养10周后,各组大鼠CHO,TG,LDL-C均增加;Ⅲ、Ⅳ、Ⅴ组大鼠血清INS水平较对照组增高,除IV外,各组胰高血糖素均高于对照组。水迷宫试验结果显示,Ⅶ组潜伏期延长,与对照组比较,具有统计学意义。结论 STZ(30 mg/kg)配合高糖高脂膳食能够快速、稳定的建立糖尿病大鼠模型,高糖高脂膳食组6周后尾静脉注射STZ(30 mg/kg)制备模型,血糖升高显著,血清胰岛素水平降低明显,倾向于1型糖尿病模型。     

The effects of streptozotocin induced diabetes mellitus and fish oil compound on gene expression of atrial natriuretic peptide in rat.

1. Adult male Wistar rats were injected with streptozotocin (STZ: 55 mg/kg) for inducing diabetes. Then blood and atria for RNA extraction were withdrawn from rats treated 3 and 11 weeks previously with STZ respectively. Atrial total RNA were extracted with cold phenol method. The ANP mRNA contents were determined using Dot blot hybridization technique with alpha-32-P-labelled r-prepro ANP cDNA probe. 2. Plasma glucose was increased and plasma immunoreactive insulin was lowered in rats at 3 and 11 weeks after injection of STZ. ANP gene expression in diabetic rats was depressed. ANP mRNA contents in rats treated 3 and 11 weeks with STZ were 86.4% and 31.7% of that of control rats. 3. Three weeks after treatment of STZ, the rats were gastrically perfused with FOC (Fish Oil Compound) (0.355 ml/kg) once a day successively until 11 weeks. This treatment induces lower blood pressure in rats. ANP gene expression in FOC group was apparently recovered which had been decreased because of the effect of diabetes mellitus.     

Impairment of transneuronal traffic in Streptozotocin-induced diabetes, a WGA-HRP neurohistochemical study in the rat

Retrograde transport of Wheat germ agglutinin conjugated to Horseradish peroxidase (WGA-HRP) was used in labeling vagal neurons projecting to the stomach from the dorsal motor nucleus of the vagus nerve (DMNV) in Streptozotocin (STZ)-induced diabetic rats. Diabetes was induced in the experimental rats by intraperitoneal injection of buffered STZ. Control rats were injected with an equivalent volume of the citrate buffer not containing STZ. The experimental rats, which became diabetic about 24 h after intraperitoneal injection of STZ, were kept alive for a period of 24 weeks to attain a chronic state of diabetes. Control euglycaemic rats were also kept alive for 24 weeks. At the end of 24 weeks, the two groups of rats were prepared for stomach surgery. Following anaesthesia laparotomy was performed and the stomach exteriorized. The anterior and posterior walls of the stomach were injected with 0.1 ml of 5% WGA-HRP in 0.5 M sodium chloride. Experimental and control rats were sacrificed 48–72 h after tracer injection by transcardial perfusion with normal saline, fixative and buffered sucrose. Transverse serial frozen sections of the brainstem were processed for WGA-HRP neurohistochemistry and analyzed under light and dark-field microscopy. The analyses of the sections taken from the chronic diabetic rats revealed fewer WGA-HRP labeled neurons in the DMNV than sections taken from the control euglycaemic rats. The depletion of labeled neurons in the diabetic rats compared with the euglycaemic rats is indicative of an interference with the mechanism of retrograde neuronal transport of WGA-HRP by chronic diabetic state.     

Early changes in pituitary adenylate cyclase-activating peptide, vasoactive intestinal peptide and related receptors expression in retina of streptozotocin-induced diabetic rats

The retinal expression and distribution of pituitary adenylate cyclase-activating peptide (PACAP) and vasoactive intestinal peptide (VIP) and their receptors was investigated in early streptozotocin (STZ)-induced diabetic rats. Diabetes was induced in rats by STZ injection (60mg/kg i.p.). PACAP, VIP and their receptors in nondiabetic control and diabetic retinas were assayed by quantitative real-time PCR and Western blot 1 and 3 weeks after STZ injection. Effects of intravitreal treatment with PACAP38 on the expression of the two apoptotic-related genes Bcl-2 and p53 were also evaluated. PACAP and VIP, as well as VPAC1 and VPAC2 receptors, but not PAC1 mRNA levels, were transiently induced in retinas 1week following STZ. These findings were confirmed by immunoblot analyses. Three weeks after the induction of diabetes, significant decreases in the expression of peptides and their receptors were observed, Bcl-2 expression decreased and p53 expression increased. Intravitreal injection of PACAP38 restored STZ-induced changes in retinal Bcl-2 and p53 expression to nondiabetic levels. The initial upregulation of PACAP, VIP and related receptors and the subsequent downregulation in retina of diabetic rats along with the protective effects of PACAP38 treatment, suggest a role for both peptides in the pathogenesis of diabetic retinopathy.     

散发性阿尔茨海默病大鼠学习记忆和抗氧化能力的观察

目的:观察散发性阿尔茨海默病动物模型的学习记忆和抗氧化能力,初步探讨该疾病的发生机制。方法:雄性SD大鼠24只,随机分为正常对照组和模型组。模型组大鼠给予侧脑室注射STZ制作散发性阿尔茨海默病动物模型,3周后,通过Morris水迷宫方法进行行为学检测,生物化学方法检测海马超氧化物歧化酶(SOD)活力、丙二醛(MDA)含量的变化。结果:与对照组比较,模型组大鼠潜逃潜伏期延长(P<0.05)、目的象限停留时间显著降低(P<0.05);海马SOD活力降低(P<0.01),MDA含量增加(P<0.01)。结论:散发性阿尔茨海默病大鼠学习记忆能力低,其发生机制可能与大鼠海马的抗氧化能力下降有关。     

Integrin-Linked Kinase Inhibition Attenuates Permeability of the Streptozotocin-Induced Diabetic Rat Retina

Integrin-linked kinase (ILK), as a multi-functional regulator, has been associated with diabetic retinopathy (DR). In this study, we investigated whether inhibition of ILK could result in therapeutic effects. Diabetes mellitus’s rats were induced by streptozotocin (STZ) injection. After 1 weeks induction, rats were injected intraperitoneally daily with ILK inhibitor, QLT0267, at 5 mg/kg. Then, the rats were examined by 4, 8, and 12 weeks after first STZ injection. We found that QLT0267 treatment could not only lower ILK level in retina at as early as 3 weeks after the onset of diabetes but also attenuate retina permeability, which was measured by Evan’s blue. Maximum effect was found in 11 weeks treatment. Meanwhile, QLT0267 did not disturbed blood glucose concentration. Furthermore, QLT0267 inhibited Akt (Ser473) activation and reduced expression of HIF1α and VEGF which were evaluated by western blot, real time PCR, and immunohistochemistry. We conclude that ILK may be a new target for DR.     

Upregulation of small GTPase RhoA in the basilar artery from diabetic (mellitus) rats

The goal of this study was to determine whether RhoA, a small GTPase, might be involved in the development of cerebral pathogenesis in diabetes. Male SD rats (n = 120) were divided into six groups: diabetic for 2, 4, 8 weeks, and an age-matched control group. Diabetes was induced by intravenous injection of streptozotocin (50 mg/kg). RhoA mRNA expression in basilar artery was measured by competitive RT-PCR. RhoA mRNA level was significantly increased in 4 weeks (184.1 +/- 28.5%, n = 7) and 8 weeks (218.7 +/- 24.5%, n = 7) after STZ injection compared to the age matched control basilar arteries (P < 0.05). Western blot was used to measure the membrane binding RhoA level to represent the activity of RhoA. We found that RhoA activity was strikingly increased in the diabetic basilar artery (n = 10 in each groups) compared to control basilar artery after STZ injection. Our data demonstrated that there was an upregulation of RhoA in the basilar artery of STZ induced diabetic rats, suggesting that RhoA might be involved in the cerebral vascular pathogenesis during diabetes mellitus.     

Effects of i.c.v. administration of leptin on copulatory and ingestive behavior in STZ-induced diabetic male rats.

It is well known that circulating leptin concentrations correlate with adiposity in both humans and rodents and decrease after fasting, energy restriction, or weight loss. The goal of the present study was to confirm whether the decreases of copulatory behavior and the increases of ingestive behavior in STZ-induced diabetic male rats could be reversed by i.c.v. administration of leptin. Adult male Wistar-Imamichi rats aged 9 weeks were used for the studies. Males received a single injection of STZ (60 mg/kg, i.p.) and vehicle. During the experiment, individual body weight, and food and water intake were measured. The copulatory and ingestive behaviors in STZ-induced diabetic males were observed at 2 and 4 weeks after STZ. At 6 weeks after STZ, leptin (10 microg/10 microl) or aCSF (artificial cerebrospinal fluid) was injected through a lateral ventricle cannula and the above two behaviors were observed again. The i.c.v. leptin injection to STZ-induced diabetic males resulted in a significant increase of ejaculation frequencies (3.6 +/- 0.26 vs. 2.9 +/- 0.30 times) and a significant decrease in amount of food ingested (36.2 +/- 1.93 vs. 23.2 +/- 3.76 g), compared with the aCSF-injected control (p<0.01). These findings suggest that the copulatory and ingestive behaviors in i.c.v. leptin-injected STZ diabetic males were restored to levels equivalent to those in control males.     

The Chronological Characteristics of SOD1 Activity and Inflammatory Response in the Hippocampi of STZ-Induced Type 1 Diabetic Rats

Because it appears that oxidative stress and inflammation are implicated with disease pathogenesis in the diabetic brain, many researchers have used streptozotocin (STZ)-induced diabetic animals to study superoxide production and the effects of superoxide scavengers like Cu,Zn-superoxide dismutase (SOD1). However, many studies have been conducted without considering temporal changes after STZ injection. Interestingly, though SOD activities were not significantly different among the groups, SOD1 and 4-hydroxy-2-nonenal (4-HNE) immunoreactivities were significantly enhanced at 3 weeks after an STZ injection (STZ3w) versus only marginal levels in sham controls, whereas microglial activity was remarkably reduced in injected rats at this time. However, SOD1 immunoreactivity and microglial activities were only at the sham level at STZ4w. The present study provides important information concerning cell damage by ROS generated by STZ. Microglial response was found to be inactivated at STZ3w and neuronal cells (NeuN) showed a non-significant tendency to be reduced in number at STZ4w except in the dentate gyrus. We speculated that the above oxidative stress-related events should be accomplished at STZ3w in the brains of STZ-induced diabetes animal models. Therefore, the aim of the present study was to investigate chronological changes in SOD1 immunoreactivity associated with lipid peroxidation and inflammatory responses in the hippocampi of STZ-induced type I diabetic rats.