Comparative study on the difference of obesity model induced by two kinds of high fat diet in Sprague-Dawley rats

Objective: To explore the differences of obese Sprague-Dawley(SD)rats model induced by lard oil high-fat(HF)diet or purified HF diet. Methods: SD weanling rats were randomly divided into three groups: D1 group,where rats were fed by lard oil HF diet;D2 group,where rats were fed by purified HF diet;C group,where rats were fed on chow. After 12 weeks,diet-induced obesity rat(stop 33% based on weight)were selected for further study,and the rest rats from group D1 and D2 were excluded. The food intake and weight were weighted daily and weekly,respectively. The subcutaneous,visceral and total fat contents of rats was measured by 256-row CT scan and the Lee index was calculated accordingly. The kidney,liver,testis,spleen and heart were weighted respectively. Serum leptin and insulin levels were quantified. The pathology in liver and adipose tissues were analyzed by HE staining. Oral glucose tolerance test(OGTT)was used to compare the glucose tolerance ability. Serum total cholestero(lT-CHO),high density lipoprotein(HDL-C),low density lipoprotein(LDL-C),triglyceride(TG)and inflammatory cytokines IL-6,TNF-α were detected as well. Results: After 12 weeks,the body weight,subcutaneous fat,visceral fat,total fat mass,wet weight of liver,kidney and heart,area under blood glucose curve and the levels of serum insulin,leptin,T-CHO,LDL-C,TG,IL-6 and TNF-α in group D2 were significantly increased compared to those of group C and group D1. HDL-C of group D2 was markedly lower than that in group C(P<0. 05). The visceral fat,total fat content and HDL-C in group D1 were significantly different from those of group C(P<0. 05). Steatosis and enlarged adipocyte were found in the livers of rats in group D1 and D2,and the lesions were more significant in group D2. Conclusion: Purified HF diet was more effective in inducing metabolic abnormalities,steatosis,peripheral chronic inflammation in obese SD rat models. But lard oil HF diet was more economical when only inducing visceral steatosis was required.

Effect of Soy Isoflavone Crude Extract Supplementation on High Fat Diet-induced Insulin Resistance in Ovariectomized Rats

Female Wister rats aged 8 weeks were randomly divided into sham operation group, ovariectomized （OVX） control group, and 20VX groups fed with soy isoflavone crude extract supplementation. The rats had free access to high fat diet and water for 9 weeks. No significant difference was found in body weight （BW）, total abdominal fat, food intake and food utilization rate between OVX control group and 20VX groups. However, the fasting blood glucose and blood lipid levels were significantly higher in 20VX groups than in OVX control group （P〈0.05）. Intraperitoneal glucose tolerance test （IGTI＂） showed that the area under AUC was smaller in 20VX groups than in OVX control group （P〈0.05）. These findings showed that soy isoflavone crude extract supplementation can improve glucose tolerance and prevent high fat diet-induced insulin resistance in ovariectomized rats.

Impact of age on host responses to diet-induced obesity:Development of joint damage and metabolic set points

Background:Osteoarthritis is one of the leading causes of pain and disability worldwide,and a large percentage of patients with osteoarthritis are individuals who are also obese.In recent years,a series of animal models have demonstrated that obesity-inducing diets can result in synovial joint damage(both with and without the superimposition of trauma),which may be related to changes in percentage of body fat and a series of low-level systemic inflammatory mediators.Of note,there is a disparity between whether the dietary challenges commence at weaning,representing a weanling onset,or at skeletal maturity,representing an adult onset of obesity.We wished to evaluate the effect ofthe dietary exposure time and the age at which animals are exposed to a high-fat and high-sucrose(HFS) diet to determine whether these factors may result in disparate outcomes,as there is evidence suggesting that these factors result in differential metabolic disturbances.Based on dietary exposure time,we hypothesized that rats fed an HFS diet for 14 weeks from weaning(HFS Weanling) would demonstrate an increase in knee joint damage scores,whereas rats exposed to the HFS diet for 4 weeks,starting at 12 weeks of age(HFS Adult) and rats exposed to a standard chow diet(Chow)would not display an increase in knee joint damage scores.Methods:Male Sprague-Dawley rats were fed either an HFS diet for 14 weeks from weaning(HFS Weanling) or an HFS diet for 4 weeks,starting at 12 weeks of age(HFS Adult).At sacrifice,joints were scored using the modified Mankin Criteria,and serum was analyzed for a defined subset of inflammatory markers(Interleukin-6,leptin,monocyte chemoattractant protein-1,and tumor necrosis factorα).Results:When the HFS Weanling and HFS Adult groups were compared,both groups had a similar percent of body fat,although the HFS Weanling group had a significantly greater body mass than the HFS Adult group.The HFS Weanling and HFS Adult animals had a significant increase in body mass and percentage of body fat when compared to the Chow group.Although knee joint damage scores were low in all 3 groups,we found,contrary to our hypothesis,that the HFS Adult group had statistically significant greater knee joint damage scores than the Chow and HFS Weanling groups.Furthermore,we observed that the HFS Weanling group did not have significant differences in knee joint damage scores relative to the Chow group.Conclusion:These findings indicate that the HFS Weanling animals were better able to cope with the dietary challenge of an HFS diet than the HFS Adult group.Interestingly,when assessing various serum proinflammatory markers,no significant differences were detected between the HTS Adult and HFS Weanling groups.Although details regarding the mechanisms underlying an increase in knee joint damage scores in the HFS Adult group remain to be elucidated,these findings indicate that dietary exposure time maybe less important than the age at which an HFS diet is introduced.Moreover,increases in serum proinflammatory mediators do not appear to be directly linked to knee joint damage scores in the HFS Weanling group animals but may be partially responsible for the observed knee joint damage in the adults over the very short time of exposure to the HFS diet.

Experimental models of non-alcoholic fatty liver disease in rats

Non-alcoholic fatty liver disease(NAFLD)is the most common chronic liver disease in the Western world,and it persists at a high prevalence.NAFLD is characterised by the accumulation of triglycerides in the liver and includes a spectrum of histopathological findings,ranging from simple fatty liver through non-alcoholic steatohepatitis(NASH)to fibrosis and ultimately cirrhosis,which may progress to hepatocellular carcinoma.The pathogenesis of NAFLD is closely related to the metabolic syndrome and insulin resistance.Understanding the pathophysiology and treatment of NAFLD in humans has currently been limited by the lack of satisfactory animal models.The ideal animal model for NAFLD should reflect all aspects of the intricate etiopathogenesis of human NAFLD and the typical histological findings of its different stages.Within the past several years,great emphasis has been placed on the development of an appropriate model for human NASH.This paper reviews the widely used experimental models of NAFLD in rats.We discuss nutritional,genetic and combined models of NAFLD and their pros and cons.The choice of a suitable animal model for this disease while respecting its limitations may help to improve the understanding of its complex pathogenesis and to discover appropriate therapeutic strategies.Considering the legislative,ethical,economical and health factors of NAFLD,animal models are essential tools for the research of this disease.

Apoptosis of Pancreatic Beta Cells in Pregnant Insulin-resistant Rats Fed with High-fat Diet

Objective The aim of this study is by observing the number change of islets beta cells in gestational rats exposed to high fat diet, tofurther reveal the mechanism of gestational diabetes mellitus. Methods Female Wistar rats were exposed to high fat diet for five weeks, and then became pregnant. During pregnancy dynamically detected indicators of glucose and fat. Until the third trimester of pregnancy evaluated the sensitivity of insulin and glucose tolerance. After executed rats, selected pancreatic tail tissue and fixed, further slides were stained with insulin antibody by immunohistochemistry to confirm the location of beta cells. Image analysis system determined mean area stained positive cells in each islet, which stood for total number of beta cells. The apoptotic beta cells in islet were detected and quantified by the Tunel technology to calculate apoptosis ratio. Results The level of free fatty acids in rats exposed to high fat diet was significantly higher than the control groups, and insulin resistance was more serious. Compared mean stained positive area among each group, the largest was gestational rats fed high fat diet, and gestational rats was larger than virgin rats, but the difference had no statistical significance. About apoptoticratio of beta cells was higher in diet intervened rats, gestational rats were higher than virgin rats. The same trend happened in the number of positive cells, but discrepancy was not remarkable. Conclusion Based on insulin resistance, apoptosis of pancreatic beta cellsincreased in gestational ratstaking high fat diet, through changing the number of beta cells to down regulate the pancreas endocrine function. That may be the mechanism of gestational mellitus.

Effect of mango seed kernel extract on the adipogenesis in 3T3-L1 adipocytes and in rats fed a high fat diet

Mangoes (Mangifera indica L.) are one of the most important tropical foods. The seed is one of the main by-products of mango processing. Therefore, it is important to find an economically viable use for this waste (e.g., as a food additive or supplement with high nutraceutical value). We investigated the anti-obesity effects of mango seed kernel extract with hot water (MSKE-W) in 3T3-L1 adipocytes and in a high fat diet (HFD)-induced obesity rat model. MSKE-W caused a significant decrease in the activity of glycerol 2-phosphate dehydrogenase in 3T3-L1 adipocytes without eliciting cell cytotoxicity and inhibited cellular lipid accumulation through down-regulation of transcription factors such as PPARγ and C/EBPα. In the animal model, rats fed an HFD containing 1% MSKE-W gained less weight than rats fed an HFD alone. The visceral fat mass in rats fed an HFD containing 1% MSKE-W tended to be lower than that in rats fed an HFD alone. Furthermore, histological examination of rat livers from an HFD showed steatohepatitis. However, rats on an HFD containning 1% MSKE-W showed no histopathological changes in liver tissue. Our results indicate that MSKE-W influences anti-obesity effects, both in vitro and in vivo, and suggest that MSKE-W provides a novel preventive potential against obesity.

Effects of octreotide on glucose transporter type 2expression in obese rat small intestine

AIM:To investigate the effects of the somatostatin analogue,octreotide,on maltose and sucrase activities and expression of glucose transporter type 2(GLUT2) in obese rat intestinal mucosa.METHODS:We divided 49 Sprague-Dawley rats into a group of 31 high fat diet-induced obese rats and a group of 18 normal controls.The obese rats were separated into an octreotide treated group of 16 rats and an obese group of 15.The intervention group was injected with octreotide at 40μg/kg body weight every 12 h for 8 d.Rat body weight was measured weekly to calculate Lee's index.After euthanization,maltase and sucrase activities in the small intestine were measuredby activity assays,and the fasting plasma glucose level was measured.The expression of GLUT2 in small intestinal mucosa was analyzed by immunohistochem-istry,reverse transcriptase polymerase chain reaction and Western blotting assays.RESULTS:Body weight,Lee's index,fasting plasma glucose level,maltase activity in small intestinal mucosa,mucosa and apical GLUT2,GLUT2 mRNA and protein expression levels were all significantly higher in the obese group than in the normal control group(605.61±141.00 vs 378.54±111.75,337.61 ±10.82 vs 318.73±20.10,8.60±1.38 vs 7.33± 0.70,156.01±58.81 vs 50.43±30.49,390 744.2 ±62 469.21 vs 170 546.50±50 646.14,26 740.18 ±3809.60 vs 354.98±57.19,0.26±0.11 vs 0.07 ±0.02,and 2.08±0.59 vs 1.27±0.38,respectively,all P<0.01).Sucrase activity did not differ between the two groups.Octreotide intervention significantly decreased the body weight and fasting plasma glucose level of obese rats(508.27±94.39 vs 605.61±141.00,7.58±1.51 vs 8.60±1.38,respectively,all P<0.05).The intestinal mucosa and apical GLUT2,expression of GLUT2 mRNA and protein were also significantly lower in the octreotide intervention group than in the obese group(269 975.2 ±53 730.94 vs 390 744.2±62 469.21,3758.06± 364.51 vs 26 740.18±3809.60,0.08±0.02 vs 0.26± 0.11,and 1.31±0.27 vs 2.08±0.59,respectively,all P<0.01).CONCLUSION:High fat dietinduced obesity is associated with elevated intestinal maltase activity,GLUT2 expression,and permanent apical GLUT2 in the small intestinal mucosa of rats.Octreotide can inhibit these effects.

HIGH-FAT-DIET INDUCED OBESITY IN RATS AND EFFECTS OF ENDURANCE TRAINING ON THE BODY FAT CONTENT OF OBESE RATS

To study the high-fat-diet induced rat obesity and the of fect of endurance training on the body fat content of obese rats, we randomly divided 66 male weanling SD rats into control(16 rats) and high fat diet group(50 rats). After 10 weeks, we chose diet-induced obese rats(DIO, 26 rats) and divided them into endurance training group(DIO-T, 8 rats) and DIO groups(DIO, 18 rats) randomly. Aner 8 weeks, endurance training, all rats were killed. The results showed that nosignificant difference was found between groups in body weight, the feed efficiency of DIO groups was higher than control groups, tke carass fat con tent of DIO-T group was significantlylower than DIO group, and plasma insulin concentration of DIO group was higher than control and DIO-T groups. It was suggested that rats’ obesity was induced obesity by high fat diet, dietary obesity had relation to higher eding efficiency and hyperinsulinemia. Endurance training can effectively reduce the body fat content of high-fat-diet induced obese rats by improving its hyper-insulinemia. Plasma TCH and TG of all rats had no significant difference.

不同高脂饲料配方对建立非酒精性脂肪肝大鼠模型的影响

目的:比较3种不同配方高脂饲料构建非酒精性脂肪肝大鼠模型的差异,提高高脂饲料建立非酒精性脂肪肝大鼠模型的成功率,为非酒精性脂肪肝病的研究提供稳定可靠的动物模型。方法:将SPF级雄性SD大鼠随机分为普通饲料对照组、高脂饲料1组(HFD1组)、高脂饲料2组(HFD2组)、高脂饲料3组(HFD3组)。各组大鼠分别给予相应饲料8周。造模期间记录大鼠一般情况、体质量和摄食量。喂养8周后,采用腹部超声、计算机断层扫描(CT)、核磁共振成像(MRI)对大鼠肝脏进行检查。取血和肝脏,检测肝功能指标(丙氨酸氨基转移酶、天门冬氨酸氨基转移酶)、血脂指标(甘油三酯、总胆固醇、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇)和炎症指标(IL-1β、IL-6、TNF-α)的变化。肉眼观察肝脏大体形态,计算其肝指数和Lee’s指数。比较上述指标在各组间的差异,综合评估不同配方高脂饲料对非酒精性脂肪肝大鼠模型的影响。结果:与对照组大鼠相比,HFD1组、HFD2组、HFD3组大鼠精神变差、活动减少、脱毛现象加重、摄食量减少、体质量明显升高,肝指数、Lee’s指数显著提高,肝脏体积增大,边缘较钝,可见脂肪变性和沉积,且以HFD3组大鼠变化最为明显;HFD1组、HFD2组、HFD3组大鼠血清谷丙转氨酶、天门冬氨酸氨基转移酶、甘油三酯、总胆固醇、低密度脂蛋白胆固醇和IL-1β、IL-6、TNF-α水平均显著升高,高密度脂蛋白胆固醇显著降低,且HFD3组更为明显;HFD1组、HFD2组、HFD3组大鼠肝脏肿大,实质回声增强,肝内管状结构显示欠清,肝和脾的CT值比值明显降低,同/反相位图上肝脏实质信号差别明显,且HFD3组对于大鼠影像学变化影响更大。结论:三种高脂饲料喂养SD大鼠8周后,均可建立非酒精性脂肪肝大鼠模型,但HFD3组诱导非酒精性脂肪肝大鼠模型优于其他两组,病变相对严重,预计维持时间也更长,更适于非酒精性脂肪肝病的机制研究和降脂药物的筛选。

高脂饲料诱导的肥胖倾向和肥胖抵抗倾向大鼠内脏脂肪visfatin和AMPK表达及其相互关系

目的:探讨大鼠内脏脂肪组织visfatin和AMPK的表达对肥胖倾向(OP)和肥胖抵抗倾向(ORP)形成的可能作用。方法:20只雄性Wistar大鼠,高脂饲料喂养10周,依据腹脂/体重比值选大鼠进入OP和ORP两组,每组各7只,测定大鼠血脂、血糖、血浆胰岛素和visfatin浓度,肾周脂肪组织中visfatin表达和AMPK活性。结果:与ORP组大鼠相比,OP组大鼠血浆visfatin浓度有升高趋势(P=0.16),肾周脂肪组织visfatin表达显著升高(P<0.05),而AMPK活性显著降低(P<0.05),内脏脂肪visfatin表达与AMPK活性之间存在负相关关系。结论:内脏脂肪组织中visfatin表达升高和AMPK活性降低可能与肥胖倾向有关。Visfatin可能通过负性调节AMPK活化程度影响肥胖倾向的发生。

痰热腑实证大鼠模型建立的条件探索

目的设置不同的高脂饮食模式以建立痰热腑实证大鼠模型,探讨不同造模条件对模型质量的影响。方法随机将36只雄性SD大鼠分为A组、B组、C组,每组12只。A组给予普通维持饲料、B组给予高脂饲料、C组给予普通维持饲料+高脂乳剂灌胃,造模周期28 d;于造模的第26天起给予B、C组大鼠自体粪便混悬液灌胃,连续3 d。比较三组大鼠一般指标、舌象指标、粪便指标和血脂水平。结果与A组比较,B、C组大鼠的日均饮食量和饮水量均较少(均P<0.05);B、C组大鼠日均饮食量和饮水量差异均无统计学意义(均P>0.05)。造模第1、2周,三组大鼠体重差异均无统计学意义(均P>0.05);造模第3周,A、B两组大鼠体重均大于C组大鼠(均P<0.05);造模第4周,B组、A组、C组大鼠体重依次降低(均P<0.05)。造模第1周,C组大鼠体温低于A、B组(均P<0.05);造模第2周,B组大鼠体温高于A、C组大鼠;造模第3周,B、C组大鼠体温均高于A组;造模第4周,B组大鼠体温高于A、C组大鼠(均P<0.05)。末次灌胃后,B、C组大鼠舌象R、G、B值均低于A组大鼠,B、C组大鼠舌下脉络评分均高于A组大鼠(均P<0.05)。与A组比较,B、C两组大鼠粪便粒数、粪便湿重、Bristol分级量表(BSFS)评分均减少/降低(均P<0.05);B、C组大鼠粪便粒数、粪便湿重、BSFS评分差异均无统计学意义(均P>0.05)。粪便灌胃后,与A组比较,B组血清总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)水平均升高(均P<0.05),C组血清TC、LDL-C水平均升高(均P<0.05);B、C组大鼠血清LDL-C、TC、TG、HDL-L水平差异均无统计学意义(均P>0.05)。结论与普通维持饲料+高脂乳剂灌胃+自体粪便混悬液灌胃法相比,高脂饲料喂养+自体粪便混悬液灌胃法造模能复制出体征症候更明显、稳定性更强、齐同性更好的痰热腑实证动物模型。

不同配方高脂饲料诱导建立大鼠高脂血症模型的比较研究

目的应用不同配方的高脂饲料,诱导建立Sprague-Dawley(SD)大鼠高脂血症模型。方法雄性SD大鼠随机分成6组:正常对照组和5个高脂模型组,连续分别饲喂普通饲料和不同配方高脂饲料6周,于诱导1、2、4和6周检测大鼠血脂含量,诱导6周后进行肝脂质含量的检测。结果与正常对照组大鼠相比,造模6周后,模型2和模型3组大鼠血清中总胆固醇(TC)含量显著升高,各模型组大鼠血清中的低密度脂蛋白-胆固醇(LDL-C)含量均显著升高;且与正常组大鼠相比,各模型组大鼠肝中的甘油三酯(TG)和总胆固醇(TC)含量也显著增加。结论通过饲喂高脂饲料6周进行诱导,添加了20%果糖和10%猪油的配方2和配方3高脂饲料能够成功建立大鼠高胆固醇血症模型,为降脂药物的研发提供了一种简单、低成本、稳定的动物模型。

运动强度与高脂饮食模型大鼠脂代谢紊乱和氧化应激的相关性

背景:肥胖是一种多因素的慢性疾病,经常运动可以改善肥胖群体脂代谢紊乱和氧化应激的现象,但不同强度运动对脂肪代谢的具体机制尚不清楚。目的:探讨不同强度运动对肥胖大鼠脂代谢和氧化应激等指标的影响,并进一步阐明过氧化物酶体增殖物激活受体α、肝X受体α及相关通路蛋白与脂代谢指标的相关性及具体作用机制。方法:将大鼠随机分为5组:即正常对照组(n=10)、肥胖模型组(n=10)、小强度运动组(n=10)、中等强度运动组(n=9)和大强度运动组(n=8),正常对照组给予普通饲料,后4组均喂饲高脂饮食,喂养16周制备肥胖大鼠模型,造模成功后各运动组每周运动5 d,每次1 h。运动6周后测试大鼠体质量、肝质量、心脏质量、体脂率、血脂、脂酶和氧化应激指标,脂肪组织病理切片观察脂肪细胞的形态和结构;用Western blot法测定肝脏中载脂蛋白A5、过氧化物酶体增殖物激活受体α、固醇调节元件结合蛋白1c和肝X受体α的蛋白表达水平。结果与结论:①与肥胖模型组相比,中等强度运动显著降低肥胖大鼠三酰甘油、低密度脂蛋白和游离脂肪酸水平(P<0.01),同时显著升高脂蛋白脂酶和肝脂酶活性(P<0.05);②各运动组中血浆丙二醛水平显著降低(P<0.01),而过氧化氢酶活性显著升高(P<0.01);③各运动组载脂蛋白A5蛋白表达水平均显著升高(P<0.05,P<0.01,P<0.01),固醇调节元件结合蛋白1c和肝X受体α的表达均降低(P<0.01),而过氧化物酶体增殖物激活受体α水平仅在中等强度运动组显著升高(P<0.05);④与小强度运动组和大强度运动组相比,中等强度运动组载脂蛋白A5水平显著升高(P<0.01,P<0.05);而与小强度运动组相比,中强度运动组固醇调节元件结合蛋白1c表达水平显著降低(P<0.01);⑤提示不同强度运动对肥胖大鼠脂代谢相关指标和氧化应激指标均有改善,中等强度运动依赖过氧化物酶体增殖物激活受体α和肝X受体α信号通路的双重调节,改善效果更优。

一种快速构建小鼠肥胖模型的方法

采用高脂饮食构建小鼠肥胖模型,发现传统高脂饲料存在适口性差、建模时间长、成模率低等问题。针对这些问题,本文通过改进传统高脂饲料配方,采用间隔喂养的方法构建C57BL/6J小鼠肥胖模型。造模组成模后检测血清生化指标、脂肪质量、肝脏、脂肪、胰腺组织病理学变化。结果表明:1)投喂改进高脂饲料均能缩短造模时间,在间隔喂养方法下仅需6周即可建成小鼠肥胖模型。2)高脂饲料组血清中肝功能、肾功能相关生化指标正常,血脂升高(P<0.01);病理学组织切片显示肝组织存在轻到中度水肿,脂肪细胞体积增大,胰腺组织未见异常。本文的改进高脂饲料适口性好,能在短时间内升高小鼠体质量,比市面上同类型的高脂饲料建模时间更短且具有食品安全性。

荷泽颗粒对高脂饮食诱导的肥胖幼龄大鼠糖脂代谢的影响及机制研究

目的探究荷泽颗粒对高脂饮食诱导的肥胖幼龄大鼠糖脂代谢的影响及机制。方法取刚断乳的3周龄SD雄性大鼠通过高脂饲料喂养建立肥胖模型,随机分成模型组、荷泽颗粒低、中、高剂量组、荷泽颗粒高剂量+LY294002组,每组12只,另选12只刚断乳的3周龄SD雄性健康大鼠通过普通饲料喂养作为对照组,以荷泽颗粒不同剂量和磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B(AKT)信号抑制剂LY294002分组处理后,检测大鼠体质量、脂体比和糖脂代谢;以HE和油红O染色分别检测大鼠肝组织病理损伤及脂肪变性;以ELISA试剂盒检测大鼠血清促炎因子白细胞介素(IL)-18、环氧化酶-2(COX-2)、IL-17水平;以免疫印迹法检测大鼠肝组织PI3K/AKT信号通路相关蛋白表达。结果与对照组比较,模型组大鼠肝组织病理损伤及脂肪变性严重,体质量、脂体比、总胆固醇(TC)及甘油三酯(TG)、低密度脂蛋白胆固醇(LDL)水平、空腹血糖、血清IL-18及COX-2、IL-17水平显著升高(P<0.05),肝组织p-PI3K/PI3K、p-AKT/AKT水平显著降低(P<0.05);与模型组比较,荷泽颗粒低、中、高剂量组大鼠肝组织病理损伤及脂肪变性均减轻,体质量、脂体比、TC及TG、LDL水平、空腹血糖、血清IL-18及COX-2、IL-17水平均降低(P<0.05),肝组织p-PI3K/PI3K、p-AKT/AKT水平均升高(P<0.05),且呈剂量依赖性;与荷泽颗粒高剂量组比较,荷泽颗粒高剂量+LY294002组大鼠肝组织病理损伤及脂肪变性加重,体质量、脂体比、TC及TG、LDL水平、空腹血糖、血清IL-18及COX-2、IL-17水平升高(P<0.05),肝组织p-PI3K/PI3K、p-AKT/AKT水平降低(P<0.05)。结论荷泽颗粒可能通过激活PI3K/AKT信号通路而抑制炎症反应,从而改善高脂饮食诱导的大鼠糖脂代谢,降低其血糖血脂水平,缓解其肥胖症状。

母鼠孕前肥胖和孕期过度增重对子鼠铁相关指标的影响研究

目的 探究母鼠孕前肥胖和孕期过度增重对子鼠离乳后铁相关指标的影响及可能机制。方法 将18只健康的SPF级Wistar雌性大鼠以1∶1∶1比例随机分为对照组(n=6)、孕前肥胖组(n=6)和孕期过度增重组(n=6),对照组全程饲喂标准饲料,孕前肥胖组于孕前6周起饲喂高脂饲料,孕期过度增重组仅于孕前10 d起饲喂高脂饲料、其余时期饲喂标准饲料。所产子鼠于哺乳期第21天离乳,36只子鼠(每组12只)纳入离乳后研究,雌雄各半,饲喂标准饲料;子鼠离乳后第7天、14天和21天检测血清/全血炎性指标和铁相关指标,前者包括白细胞介素-6(IL-6)和铁调素,后者包括铁蛋白、血红蛋白(Hgb)、平均血红蛋白量(Mch)和平均红细胞体积(Mcv)。结果 孕前肥胖组母鼠孕前体重显著高于对照组[(327.7±27.0)g vs.(279.3±14.2)g,P<0.01],孕期过度增重组母鼠孕期增重均值超过对照组24.4%[(108.2±17.9)g vs.(87.0±12.0)g]。与对照组子鼠相比,孕前肥胖组和孕期过度增重组子鼠离乳后第7、14和21天铁蛋白水平显著升高,孕前肥胖组雌性子鼠离乳后第7天Mch水平偏低[(21.2±0.7) pg vs.(22.5±0.7)pg,P<0.05],孕期过度增重组雌性子鼠离乳后第7天Hgb[(96.3±3.9)g/L vs.(103.3±2.7)g/L]和Mch水平[(21.2±1.1) pg vs.(22.5±0.7)pg]偏低(P<0.05);未见孕前肥胖与孕期过度增重对雄性子鼠铁相关指标的显著影响。调整炎性指标后,母鼠孕前肥胖与孕期过度增重对子鼠铁蛋白和Hgb的影响不再具有统计学意义。结论 母鼠孕前肥胖和孕期过度增重影响雌性子鼠离乳后铁相关指标,炎症反应是可能机制之一。

槲皮素改善代谢综合征实验研究

目的:观察槲皮素对高脂肪/高果糖饮食诱导大鼠代谢综合征的干预作用。方法:60只大鼠随机分为正常组、模型组、阳性对照组(二甲双胍100 mg/kg)、槲皮素3个剂量组(50、100、200 mg/kg)各10只,用17%脂肪/17%果糖饲料加20%果糖水每天饲喂构建代谢综合征模型,8周后开始灌胃给药,连续给药8周。末次给药后称量各组体质量、腹部脂肪质量,采血检测空腹血糖水平,取血清检测总胆固醇(total cholesterol,TC)、甘油三酯(triglyceride,TG)、低密度脂蛋白(low-density lipoprotein cholesterol,LDL-C)、高密度脂蛋白(high density lipoprotein cholesterol,HDL-C)、胰岛素水平,计算胰岛素抵抗指数(insulin resistance index,IRI)。结果:高脂肪/高果糖饮食诱导的大鼠代谢综合征模型符合其诊断标准,与模型组比较槲皮素高、中、低剂量组体质量和腹部脂肪质量均降低,血清TC、TG、LDL-C水平降低,HDL-C水平增高,组间差异均有统计学意义(P<0.01)。与模型组比较槲皮素高、中、低剂量组空腹血糖和胰岛素水平降低(P<0.01),高、中剂量组IRI下调(P<0.05)。结论:槲皮素对大鼠代谢综合征具有改善作用,可能与减肥降重、调控糖脂代谢、缓解胰岛素抵抗等环节有关。

不同配方高脂饲料构建SD大鼠肥胖模型的实验研究

目的:研究不同配方高脂饲料对构建SD大鼠肥胖模型成功率的影响。方法:40只5周龄雄性SD大鼠随机分成4组:C组(SPF级繁殖鼠料),H1组(40%自配高脂饲料)、H2组(45%高脂饲料)、H3组(60%高脂饲料),每组10只。每周称量大鼠体重,饲养11周后大鼠麻醉处死,测量每只大鼠的体长、脂肪重量(肾周脂肪和附睾脂肪),计算其脂体比、BMI和Lee’s指数;检测大鼠的血清总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)浓度。分析各组间上述指标的差异性,综合评估不同配方饲料对SD大鼠肥胖的影响。结果:(1)H2组大鼠自第8周体重显著高于对照组(P<0.05),且建模效率最高;(2)45%高脂饲料显著升高大鼠血清TC、TG和LDL-C浓度,而显著降低HDL-C浓度(P<0.05);(3)60%高脂饲料极显著升高大鼠血清TC和TG浓度(P<0.01),显著升高LDL-C浓度(P<0.05),而极显著降低HDL浓度(P<0.01);H2和H3组大鼠肾周脂肪重量、附睾脂肪重量、脂体比和Lee’s指数显著高于对照组。结论:(1)构建SD大鼠肥胖模型成功的判断标准:高脂饲料组体重显著增加,TC、TG、LDL-C显著升高,HDL-C显著降低,脂体比显著增加,Lee’s指数显著升高;且个体体重超过对照组平均体重20%。(2)喂饲6周是利用45%脂供能高脂饲料构建SD大鼠肥胖模型最经济的建模周期。

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% 。

高脂喂养联合链脲佐菌素注射的糖尿病大鼠模型特征

目的观察高脂喂养联合低剂量STZ注射的Sprague Dawley(SD)大鼠2型糖尿病模型的代谢特征、病理学以及胰岛分子生物学变化.方法4周龄雄性SD大鼠36只随机分为三组:(1)正常对照组(Control)9只,普通饲料喂养.(2)高脂组(High Fat chow,HE)9只,高脂饲料喂养,为普通饲料中添加20%脂肪(猪油和蛋黄粉各50%)和20%蔗糖.(3)糖尿病组(DM)18只.喂养4周后腹腔注射STZ(40 mg/kg).所有大鼠做灌胃葡萄糖耐量(OGTY)试验.放免法测定血清胰岛素,免疫组化染色观察胰岛β细胞的形态学特点,彩色图像分析系统测定胰岛素表达量,RT-PCR测定胰腺β细胞胰岛素mRNA表达水平.结果糖尿病大鼠空腹血糖(FBG)、胰岛素水平(FINS)显著高于Control组和HE组大鼠(P＜0.01),空腹血清甘油三酯(TG)和游离脂肪酸(FFA)水平显著高于Control组(P＜0.05);胰岛β细胞吸光度(A)显著低于高脂组大鼠(P＜0.05),降低11.6%.胰岛素免疫反应阳性区占胰岛百分比显著低于Control组和HE组,分别下降31.9%(P＜0.05)和43.1%(P＜0.01).胰岛素mRNA表达水平显著低于HE组(P＜0.05).STZ注射后48 h(基线值)大鼠FBG水平的分布情况为:A组(FBG＜10.0 mmol/L)占7/18;B组(FBG 10～19.9 mmol/L)占5/18;C组(FBG≥20mmol/L)占6/18.STZ注射后9 d的0GTT结果与基线值相比,B组OGTT值总体变化最小,A组FBG的变异最大,达到25%.结论高脂喂养联合低剂量STZ注射的糖尿病大鼠模型模拟2型糖尿病发生的主要病理生理过程,具有高血糖、高胰岛素血症以及血脂异常等基本特征.