西布曲明对谷氨酸钠诱导的肥胖动物模型的影响

目的　评价西布曲明 (Sibutramine ,Meridia ,MR)对肥胖动物的减肥作用。方法　取刚出生d 1的大鼠 ,♀♂兼用 ,皮下注射谷氨酸钠 (MSG) 3mg·g-1·d-1,连续 5d ;以诱导动物产生肥胖。在造型后 2 1d ,将肥胖动物按体重随机均分为 5组 ,分别灌胃MR 2 0、4 0和 8 0mg·kg-1·d-1;安菲拉酮 6 0mg·kg-1·d-1,模型组和对照组则均给 0 5 %CMC10ml·kg-1·d-1,连续 2 8d。在实验结束时 ,取样检测各指标。结果　研究显示 ,MR可使MSG诱导的肥胖大鼠体重增加减慢 ,使其脂肪垫重量及其Lees指数减少 ,脂肪细胞直径变小 ,脂肪细胞数 (一个视野内 )增加 ,使MSG大鼠血清甘油三酯降低 ,使其在禁食状态下降低的血糖及胰岛素水平恢复正常。MR对MSG的作用主要是降低其TG水平 ,而对TC无明显作用。结论　试验结果显示MR具有调节和改善脂质代谢及明显的减肥作用     

基于数据挖掘的肥胖动物模型分析

目的 通过研究肥胖动物模型的造模要素及检测指标,为建立简单易行且符合发病机制的动物模型提供参考。方法 通过在中国知网、万方、维普数据库检索2012年1月1日至2022年12月30日收录的肥胖动物实验文献,通过纳入及排除标准整理归纳实验动物种类、造模方式、检测指标、方法等建立数据库,使用Excel进行数据分析。结果 筛选纳入文献共204篇,肥胖动物实验造模多选用SD大鼠;造模方式多为饮食诱导,饮食诱导以高脂饲料为主,化学诱导药物以谷氨酸钠为主;检测指标包括血清生化指标、组织病理学、相关指数等。结论 肥胖动物实验通常选用SD大鼠,饮食诱导以配比不同的高脂饲料为主,化学诱导为谷氨酸钠皮下注射,手术诱导选择双卵巢切除术。     

营养性肥胖动物模型的实验研究

目的　观察高脂饲料配方对制造营养性肥胖动物模型成功率的影响。方法　用改进的高脂饲料喂养大鼠 16wk ,观察体重及肥胖指标 ,并与普食组进行比较。结果　高脂饲料和普通饲料喂养的大鼠体重分别为 (491 6 2± 4 6 89)g、(394 2 0± 5 0 78) g ,Lees指数分别为 319 0 4± 9 4 9、30 4 6 3± 5 99,经统计学处理 ,高脂组优于普食组 (P <0 0 1,P <0 0 5 )。造模成功后 ,高脂组大鼠的附睾脂肪量、肾周脂肪量、心包脂肪量及肝、肾重量均大于普食组 ,两组比较差异有显著性。 (P <0 0 1)。结论　含 12 %猪油、总油脂量为 18%的高脂饲料致肥效果较好 ,配方组成较为合理 ,致肥率达 5 8 9% ,高于以前文献报道     

Studies on the anti -obesity effects of betaphrine in obese animal induced by monosodium -1- glutamate

Aim： To investigate the effect of anti - obesity of Betaphring as a new anti - obesity drug in obese animal models. Methods： Obese rats was induced by SC MSG. Neonatal rats were given MSG 3mg. g^-1 continuously for 5 days from the first birthday. On the 21th day, the MSG rats were divided into six groups and administrated orally Betaphrine10, 30, 90mg. kg^-1. d^-1 or Sibutramine 4 mg. kg^-1. d ^-1 or 0. 9% NS for 28 days respectively. At the end of the experiments, the animal samples were examined. RESULTS： Betaphrine30, 90mg. kg^-1. d^-1 ig for 4wk could decrease body weight, the areas of adipose cell, the total weight of white adipose tissue and brown adipose tissue, and increase the level of serum HDLc and the number of adipose cell in the sample obese rats. But no effect was shown on the level of serum glucose, triglyceride, ins, npy, leptin , Lee＇s index, and the level of ins, npy, leptin in hypothalamus homogenate. CONCLUSION： Betaphrine is an effective agent of anti - obesity effect in MSG obese rats.     

有氧运动对肥胖大鼠心肌细胞凋亡及抗肥胖作用影响的研究

目的揭示肥胖以及有氧运动对大鼠心肌细胞的影响、肥胖大鼠的血清的TG、TC、HDL-c、LDL-c水平的变化。方法通过对大鼠进行肥胖造模、标本采集、指标测定、图像分析、统计处理,观察有氧运动能否降低肥胖大鼠的体质量、减少心肌细胞凋亡、研究其分子生物学机制以及与氧化、抗氧化物、NO水平及TNF-α表达水平,并进行初步的机制的探讨,阐明肥胖者心脏结构和功能受损的发病机制。结果肥胖大鼠发生心肌细胞损害,血清中TG、TC、HDL-C、LDL-C均增高,发生心肌凋亡的比率高,经长期运动干预后,情况改善。结论长期有氧运动可以降低肥胖大鼠与肥胖抵抗大鼠的体质量,减少心肌凋亡。     

肝损伤动物模型研究进展

已知多种致病原因可导致肝损伤 ,如病毒性肝炎、酒精性肝炎和药物性肝炎等。各种有害因素所致的肝损伤可表现为肝坏死、脂肪肝、胆汁郁积、肝纤维化、肝硬化及肝癌等。对肝损伤的防治目前仍是一个全球性的严峻课题。通过建立实验性肝损伤动物模型 ,研究肝病的发生机制 ,筛选保肝药物 ,探索保肝作用原理 ,具有十分重要的现实意义。现将近几年来国内外对实验性肝损伤动物模型分类、造模方法、检测指标及造模剂作用原理等有关方面的研究进展情况作一综述。1　化学性肝损伤动物模型1 1　四氯化碳性肝损伤　四氯化碳 (ＣＣｌ4)溶于精制植物油。急…     

老年性痴呆动物模型研究进展

老年性痴呆 (Alzheimersdisease,AD)是以老年斑和神经纤维缠结为特征的一种进行性、退行性神经系统疾病。AD动物模型的研究可大大促进AD病因、发病机制及药物筛选的研究 ,是深入开展AD研究的必要条件之一。损伤性、自然衰老动物和复合型动物模型能够复制出认知缺损等表现 ,但缺乏AD的特征性病变。SAM P/ 8是相对理想的模型。转基因小鼠是目前研究的热点 ,为在体研究AD的特定发病基因及其代谢产物提供了新的载体。随着AD治疗学由对症治疗转向对因治疗 ,AD模型也应顺应这一发展。     

绿茶提取物AR25（Exolise）的抗肥胖作用

AR25(Exolise)是绿茶的80%乙醇提取物的干浸膏,主要含25%的儿茶素类[以表棓儿茶素棓酸酯(EGCG)计]和5%～10%的咖啡因。每粒 Exolise 胶囊含375mg 的AR25。体外试验显示,AR25完全抑制胃脂酶和胰脂酶的活性,抑制甘油三酯的脂解,降低胃内脂肪酸的释放,并能刺激热产生。作者基于 AR25的上述体外活性又进行了人体研究。10位健康男性随机给予以下3种处理之     

老年性痴呆动物模型研究进展

老年性痴呆 (Alzheimersdisease ,AD )是一种进行性的神经退行性疾病 ,临床主要表现为中枢认知功能障碍 ,老年斑、淀粉样蛋白沉积及神经元纤维缠结 (NFT)是其脑部主要的病理学特征。由于AD的发病机制尚不清楚 ,给AD模型动物的研制带来了很大困难。自然衰老动物模型、损毁模型、脑室注射模型及自身免疫模型虽表现有中枢学习记忆功能的衰退 ,但缺乏AD脑内特征性的病理学变化。转基因模型虽然是十分有希望的模型 ,但目前的转基因模型尚不能全面反映AD的特征。因此 ,迄今为止还没有一个能够准确反应AD特征的理想的动物模型。比较而言 ,SAMP8是一个较好的AD替代模型 ,它既有AD学习记忆功能障碍的特征 ,又有部分AD病理学的特征。目前自身免疫模型和转基因模型已成为AD模型研究的新热点。研究并建立可靠的AD动物模型对于探明AD的发病机制以及防治药物的研究均具有重要的意义     

The utility of animal models to evaluate novel anti-obesity agents

The global incidence of obesity continues to rise and is a major driver of morbidity and mortality through cardiovascular and cerebrovascular diseases. Animal models used in the discovery of novel treatments for obesity range from straightforward measures of food intake in lean rodents to long-term studies in animals exhibiting obesity due to the continuous access to diets high in fat. The utility of these animal models can be extended to determine, for example, that weight loss is due to fat loss and/or assess whether beneficial changes in key plasma parameters (e.g. insulin) are evident. In addition, behavioural models such as the behavioural satiety sequence can be used to confirm that a drug treatment has a selective effect on food intake. Typically, animal models have excellent predictive validity whereby drug-induced weight loss in rodents subsequently translates to weight loss in man. However, despite this, at the time of writing orlistat (Europe; USA) remains the only drug currently marketed for the treatment of obesity, with sibutramine having recently been withdrawn from sale globally due to the increased incidence of serious, non-fatal cardiovascular events. While the utility of rodent models in predicting clinical weight loss is detailed, the review also discusses whether animals can be used to predict adverse events such as those seen with recent anti-obesity drugs in the clinic.     

骨骼肌中脑源性神经营养因子的表达与中枢性肥胖的相关性研究

目的研究小鼠骨骼肌中脑源性神经营养因子(BDNF)与中枢性肥胖的相关性。方法将50只新生健康小鼠随机分为对照组20只和实验组30只。实验组自小鼠出生当天起,按3 mg·g^-1·d^-1的剂量颈部皮下注射10%谷氨酸钠,连续5 d;对照组同法注射等剂量0.9%NaCl。根据实验要求对小鼠进行剔除,最终对照组和实验组各12只小鼠。每2周测定小鼠体重并计算Lee’s指数,每周测定体温。8周末取血,检测血清中血脂含量,分离肾周白色脂肪(WAT)和肩胛间棕色脂肪(BAT)并称重。用Western blotting法检测骨骼肌中BDNF的表达水平。结果6周末,实验组和对照组的体重分别为(39.71±2.55)和(32.83±2.30)g,Lee’s指数分别为(365.02±3.83)和(337.54±4.10)g^1/3·cm^-1,8周末,实验组和对照组的体重分别为(48.12±3.61)和(39.51±3.52)g,Lee’s指数分别为(361.93±7.12)和(325.17±6.87)g^1/3·cm^-1,差异均有统计学意义(P<0.05,P<0.01或P<0.001)。实验组和对照组的6周末体温分别为(36.30±0.07)和(36.67±0.07)℃,7周末体温分别为(36.40±0.08)和(36.79±0.10)℃,8周末体温分别为(36.31±0.09)和(36.80±0.10)℃,差异均有统计学意义(均P<0.05)。8周末,实验组和对照组的总胆固醇分别为(2.91±0.25)和(1.86±0.51)mmol·L^-1,三酰甘油分别为(1.48±0.62)和(0.81±0.23)mmol·L^-1,低密度脂蛋白分别为(0.37±0.06)和(0.29±0.05)mmol·L^-1,WAT分别为(0.75±0.08)和(0.24±0.05)g,BAT分别为(0.31±0.07)和(0.17±0.01)g,BAT/WAT分别为(0.41±0.08)和(0.71±0.12),BDNF相对表达量分别为(0.63±0.07)和(0.98±0.06),差异均有统计学意义(P<0.05,P<0.01或P<0.001)。结论骨骼肌中BDNF表达下调,可能通过影响能量代谢,导致小鼠中枢性肥胖。     

Atorvastatin improves insulin sensitivity in mice with obesity induced by monosodium glutamate

Aim:

To examine the mechanisms underlying the effects of atorvastatin on glucose and lipid metabolism.

Methods:

Mice with insulin resistance and obesity induced by monosodium glutamate (MSG) were used. Atorvastatin (80 mg·kg⁻¹·d⁻¹) or vehicle control treatment was given orally once a day for 30 days. Plasma levels of total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and free fatty acids were monitored. Serum insulin and glucose concentrations were used to calculate the insulin resistance index and insulin sensitivity index using a homeostasis model. Body length, waistline circumference, intraperitoneal adipose tissue mass, and total body mass were measured. Semi-quantitative RT-PCR and Western analysis were used to determine the expression of inflammatory factors and proteins involved in inflammation signaling pathways.

Results:

Atorvastatin improved insulin sensitivity, ameliorated glucose tolerance, and decreased plasma levels of total cholesterol, triglycerides, LDL-C, HDL-C and free fatty acids. Semi-quantitative RT-PCR and Western analysis revealed increased expression of interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) in serum and adipose tissue in MSG obese mice. Atorvastatin treatment decreased expression of IL-6, TNF-α, nuclear factor κB (NF-κB) and I-kappa-B (IκB) kinase-β, but increased the expression of IκB, in adipose tissue.

Conclusion:

Atorvastatin is a potential candidate for the prevention and therapy of diseases associated with insulin resistance such as type 2 diabetes mellitus and cardiovascular disease. One possible mechanism underlying the effects of atorvastatin on glucose and lipid metabolism may be to ameliorate a state of chronic inflammation.     

动物肝硬化模型构建的研究进展

肝硬化是肝纤维化发展的最终病理组织学结果,肝纤维化逐渐形成假小叶,肝脏组织逐渐发生变形和变硬,最终发展为肝硬化。建立合适的肝硬化模型,对于外科治疗经验的积累具有非常重要的作用,然而从目前的动物肝硬化模型构建结果来看,尚未有一种较为适宜的方法。本文总结和讨论了不同肝硬化模型制备方法的优缺点。这一综述将对完善动物肝硬化模型构建和开展肝硬化相关治疗和药物开发都具有一定参考价值。     

心肌缺血模型的制作方法研究进展

心肌缺血(myocardial ischemia)是心脏的血液灌注减少,导致心脏的供氧减少,心肌能量代谢异常,不能支持心脏正常工作的一种病理状态。心血管疾病康复机制研究的关键技术之一是复制心肌缺血动物模型。建立适当的动物模型,不仅为该病的发病机制和病理生理改变提供重要的资料,更重要的是能促进新药的开发,推进临床诊断和各种治疗方法的进步。该文全面总结归纳了急性心肌缺血、慢性心肌缺血、可控性心肌缺血和离体心肌缺血四类心肌缺血模型的制作方法以及各自的特点,为该疾病模型的制作与选择提供参考。     

药物过敏动物模型研究进展

药物过敏是药物临床应用和临床前研究面临的一个严重问题,预测性差,发生机制尚未明确,主要分为系统综合征和药物性皮肤反应2类。目前认为,其发生机制可能是药物通过直接或间接途径引发机体免疫病理反应。制备理想的动物模型是研究其作用机制的关键环节,最常用的模型动物有豚鼠、大鼠、小鼠和兔,在一些特殊药物实验中也使用猫、犬和猪。不同药物过敏动物模型的制备方法不同,评价方法和检测指标也不尽相同。结合相应的超敏反应病理学检测指标,探索建立适当的动物模型和合理评价体系,有助于提高对药物过敏的预测性。     

Laboratory animals as surrogate models of human obesity

Obesity and obesity-related metabolic diseases represent a growing socioeconomic problem throughout the world. Great emphasis has been put on establishing treatments for this condition, including pharmacological intervention. However, there are many obstacles and pitfalls in the development process from pre-clinical research to the pharmacy counter, and there is no certainty that what has been observed pre-clinically will translate into an improvement in human health. Hence, it is important to test potential new drugs in a valid translational model early in their development. In the current mini-review, a number of monogenetic and polygenic models of obesity will be discussed in view of their translational character.     

A brief review on recent developments in animal models of schizophrenia

Number of patients suffering from schizophrenia is increasing daily, subsequently, increasing the need of proper medication to treat the symptoms and eventually improve the patients' condition. However, all the progress for designing or discovering medication comes to a standstill, as the symptomatic treatment can only be done in the patients, but performing clinical trials with all the possible candidate drugs in human beings and patients is unethical. Thus, the need arises for proper animal and non-human primate animal models of the disease, which would not only serve the purpose of understanding the disease in a better physiological setting, but also would allow the scientists to focus on developing a therapeutically effective and potent medication for treating this hazardous disease. This brief review article focuses on a few animal models which are generally used for carrying out studies on schizophrenic symptoms in research labs and industry worldwide. The paper also tries to validate the pre-clinically available models based on certain specified criteria like the predictive constructive and face validity. Thus, the paper gives guidance toward the mechanistic and traditional models of schizophrenia applying some of the newer principles and helps researchers in deciding a particular relevant model for their own purpose.