七氟醚对C57小鼠海马基因表达的影响

目的:通过微阵列分析来研究七氟醚对小鼠海马基因表达的影响。方法:出生后第7天(P7)C57BL/6雄性小鼠12只,随机分为2组(n=6),重复七氟醚组(RS组)和空气对照组(C组),每天暴露于七氟醚(浓度为2.5%)或空气2 h,连续5 d,小鼠处死后提取海马RNA进行基因表达谱分析。结果:与C组相比,RS组共有30个基因发生了显著变化(1.5或1.5倍),其中上调基因16个(P0.05),下调基因14个(P0.05)。这些基因主要参与学习记忆、认知、细胞代谢、信号转导和通讯、结构和囊泡过程、生命物质结合和定位等过程。实验随机选择9个差异基因验证芯片结果,发现3个上调基因(Ppp1r1b、Id1和Txnip)和5个下调基因(Arc、c-Fos、Npas4、Grin2a和Kcnj2)。结论:七氟醚可引起小鼠海马中一些关键基因的改变,这些改变可能与认知功能障碍或其他神经系统疾病有关。     

CCL20增强HBsAg的免疫应答效应

目的为探讨CCL20对HBsAg介导的免疫应答是否具有增强作用,为CCL20这一细胞因子作为新型乙肝制剂的应用研究提供理论依据。方法采用基因重组技术,构建趋化因子CCL20和表面抗原（HBsAg）的真核表达载体,将重组载体用肌肉免疫的方式分别注射正常的C57BL/6小鼠,通过ELISA方法检测C57BL/6小鼠的抗-HBs抗体水平、细胞增殖情况。结果用CCL20/HBsAg真核表达质粒共注射免疫后,100%小鼠能在第4、6周检测到教高效价的抗-HBs抗体,持续时间长达10周;同时,CCL20增强了HBsAg的细胞免疫反应。结论CCL20能增强小鼠针对HBsAg的体液和细胞免疫应答反应,这将为新型乙肝特异性免疫治疗应用研究提供依据。     

The tail pigmentation pattern of C57BL/6J mice affects nociception/pain quantification in the tail flick test

The heat radiant tail flick test is commonly used to quantify nociception and pain levels. Likewise, the C57BL/6J strain of mice is frequently used in pain‐related studies as transgenic mice are often backcrossed onto this background. C57BL/6J mice naturally develop non‐pigmented patches of variable length on the distal part of the tail that could conceivably modify the response latency in tail flick assays. Here we find that these non‐pigmented regions, in a position‐independent manner, significantly increase the response latency in the heat radiant tail flick assay, but not the warm water immersion test. This finding demonstrates that the extent of pigmentation, and not other potential variables between pigmented and non‐pigmented skin, affects radiant heat tail flick latency, and should be considered in the design of pain‐related studies using mice with variable tail pigmentation.     

Intrinsic Activity of C57BL/6 Substrains Associates with High-Fat Diet-Induced Mechanical Sensitivity in Mice

Pain is significantly impacted by the increasing epidemic of obesity and the metabolic syndrome. Our understanding of how these features impact pain is only beginning to be developed. Herein, we have investigated how small genetic differences among C57BL/6 mice from 2 different commercial vendors lead to important differences in the development of high-fat diet-induced mechanical sensitivity. Two substrains of C57BL/6 mice from Jackson Laboratories (Bar Harbor, ME; C57BL/6J and C57BL/6NIH), as well as C57BL/6 from Charles Rivers Laboratories (Wilmington, MA; C57BL/6CR) were placed on high-fat diets and analyzed for changes in metabolic features influenced by high-fat diet and obesity, as well as measures of pain-related behaviors. All 3 substrains responded to the high-fat diet; however, C57BL/6CR mice had the highest weights, fat mass, and impaired glucose tolerance of the 3 substrains. In addition, the C57BL/6CR mice were the only strain to develop significant mechanical sensitivity over the course of 8 weeks. Importantly, the C57BL/6J mice were protected from mechanical sensitivity, which may be based on increased physical activity compared with the other 2 substrains. These findings suggest that activity may play a powerful role in protecting metabolic changes associated with a high-fat diet and that these may also be protective in pain-associated changes as a result of a high-fat diet. These findings also emphasize the importance of selection and transparency in choosing C57BL/6 substrains in pain-related research.

不同浓度顺铂对C57BL/6小鼠卵巢功能的影响

目的:通过研究不同浓度顺铂对C57BL/6小鼠卵巢功能的影响,探讨能够引起C57BL/6小鼠卵巢早衰的最低有效浓度,从而为临床研究提供一种安全、可靠、便捷的早发性卵巢功能不全(POI)模型构建方案。方法:随机选择SPF级雌性C57BL/6小鼠(6~8周)60只,随机分为对照组、剂量1.0组(1 mg/kg)、剂量1.5组(1.5 mg/kg)、剂量2.0组(2 mg/kg),给药组均连续腹腔注射7 d顺铂。结果:1.0组小鼠卵巢受损较轻,卵巢组织形态、卵泡计数及血清激素水平与对照组相比,变化程度较小,无法用于建模;1.5组小鼠卵巢受损较重,体质量下降平稳,一般状态好,死亡率低,动情周期恢复率低,卵巢组织形态、卵泡计数及血清激素水平与对照组差异均有统计学意义(P<0.05),但变化较为平缓,适宜建立POI模型;2.0组小鼠卵巢受损严重,体质量下降明显,全身状况差,出现持续的动情间期,卵巢组织形态、卵泡计数及血清激素水平与对照组差异均有统计学意义(P<0.05),但变化大,不利于实验研究。结论:1.5 mg/kg为建立C57BL/6小鼠POI模型的合适有效浓度,采用该给药方案建立的模型,卵巢组织损伤较为稳定,能够较好地模拟POI患者的激素水平变化,动物耐受性好,有利于治疗研究的开展,适用于POI治疗方案的评价。     

长期小强度跑台运动对C57BL/6J小鼠突触可塑性的影响

目的:本研究观察长期小强度跑台运动对C57BL/6J小鼠突触可塑性的影响,探讨运动提高学习和记忆能力的细胞机制。方法:3月龄雌性C57BL/6J小鼠随机分为运动组(12只)和对照组(12只)。运动组小鼠进行5个月小强度跑台训练,运动训练结束后进行Morris水迷宫检测学习和记忆行为学改变,1周后采用电生理学方法在体记录海马齿状回(DG)的群体峰电位(PS)和场兴奋性突触后电位(f-EPSP)的变化。电生理学测试后制备小鼠脑石蜡切片,采用免疫组织化学方法检测海马DG区突触素(SYP)的蛋白表达情况,并取海马组织利用Western blot方法检测SYP的蛋白表达。结果:电生理学结果显示,高频刺激后运动组小鼠PS幅值和f-EPSP斜率百分数均高于对照组,差异具有显著性(P0.05);运动组小鼠海马组织突触素蛋白表达水平明显高于对照组,差异具有显著性(P0.05);运动组小鼠海马齿状回突触素阳性反应产物的整合光密度值明显高于对照组,差异具有显著性(P0.05)。结论:5个月小强度跑台运动可增强C57BL/6J小鼠的突触结构和功能可塑性。     

双歧杆菌对高脂饮食诱导的C57BL/6小鼠非酒精性脂肪肝的影响

目的 探讨双歧杆菌是否通过改变肠道菌群,减少肠道局部炎症,调节系统性炎症,从而减轻高脂饮食诱导的C57BL/6小鼠的非酒精性脂肪性肝病（non-alcoholic fatty liver disease, NAFLD）。方法 将32只雄性C57BL/6小鼠作为实验动物,分为对照饲料组、对照饲料加双歧杆菌干预组、高脂饲料组和高脂饲料加双歧杆菌干预组,每组分2笼,每笼4只。检测小鼠血清糖脂代谢及肝功能水平。通过油红O染色和苏木精-伊红（H-E）染色评估小鼠肝脏脂肪变性情况。采用实时荧光定量PCR检测小鼠回肠、结肠组织中肿瘤坏死因子-α(TNF-α)、白细胞介素6(IL-6)和肠黏膜闭锁小带蛋白1(zonula occludens 1,ZO-1)、紧密连接蛋白（occludin）的表达。通过Illuminate Miseq平台微生物多样性测序检测小鼠粪便中肠道菌群的结构变化。结果 高脂饲料加双歧杆菌干预组C57BL/6小鼠肝脏脂肪变性程度明显低于高脂饲料组。与高脂肪饲料组相比,高脂饲料加双歧杆菌干预组炎症因子TNF-α、IL-6表达明显下降,肠道炎症减轻。与对照饲料组相比,高脂饲料组肠道菌群...     

Anti-obesity effects of traditional and standardized meju in high-fat diet-induced obese C57BL/6J mice

The aim of the study was to evaluate the anti-obesity effects of two types of meju in diet induced obese C57BL/6J mice. Animals were randomly divided into 4 dietary group (n = 10); normal diet, high fat diet with 30% soybean, high fat diet with 30% traditional meju, high fat diet with 30% standardized meju. After 16 weeks, after animals were sacrificed. It was observed that the high fat diet with 30% traditional meju and high fat diet with 30% standardized meju significantly reduced body weight gain, epididymal fat weight, serum triglyceride along with serum insulin and leptin levels compared to the high fat diet with 30% soybean. And also, the expression levels of hepatic lipid anabolic genes were significantly decreased in the high fat diet with 30% traditional meju and high fat diet with 30% standardized meju compared to the high fat diet with 30% soybean. In conclusion, the assessment of all the obesity markers strongly advocate the anti-obesity effect of traditional as well as standardized meju in diet induce obesity conditions.     

高脂膳食及有氧运动对C57BL/6小鼠骨骼肌基因表达谱的影响

目的:运用基因芯片技术研究高脂膳食及有氧运动因素对C57BL/6小鼠骨骼肌基因表达谱的影响,初步探寻有氧运动改善机体胰岛素抵抗(IR)相关基因的机制。方法:选用C57BL/6雄性小鼠80只,随机分为正常饮食组和IR模型组,分别饲以基础和高脂饲料10周。鉴定高脂膳食组IR小鼠模型建立成功后,将正常饮食组随机分为正常饮食安静组(NC)和正常饮食运动组(NE),IR模型组分为高脂饮食安静组(HC)和高脂饮食运动组(HE)。运动方案采用强度为75%VO2max有氧跑台训练,持续6周。后分离各组小鼠股四头肌,提取总RNA,经荧光标记后进行芯片杂交,利用芯片扫描仪记录荧光信号,并通过相关软件对所得数据进行统计分析。结果:HC/NC共筛选差异表达基因136个;NE/NC筛选差异表达基因74个;筛选HE/HC差异表达基因29个;HE/NC差异表达基因共252个,其中170个基因(HE/NC-DF)的差异表达由高脂膳食和运动因素共同引起;HE/HC中16个基因为与HE/NC-DF共同差异基因。结论:高脂膳食及有氧运动对小鼠骨骼肌基因表达均有显著影响,本研究初步筛选出有氧运动改善IR潜在相关基因,为进一步研究有氧运动改善IR分子机制提供了理论依据。     

Introduction of the human PLTP transgene suppresses the atherogenic diet-induced increase in plasma phospholipid transfer activity in C57BL/6 mice

The human plasma phospholipid transfer protein (PLTP) has been shown to facilitate the transfer of phospholipids between lipoproteins and convert high-density lipoproteins into larger and smaller particles in vitro. To explore the lipid transport function in vivo, transgenic C57BL/6 mice that express the human PLTP gene, driven by its natural promoter, were generated. Little difference in PLTP activity and lipoprotein lipids was observed between transgenic mice and non-transgenic control mice fed the chow diet. In response to an atherogenic high-fat, high-cholesterol, cholic acid containing diet, the PLTP activity increased significantly with time in control mice (62% in males and 34% in females after the high-fat diet for 18 weeks). In contrast, the PLTP activity did not change appreciably in the transgenic mice fed the atherogenic diet. Thus, the introduction of the human transgene suppressed the diet-induced increase in plasma PLTP activity, as evidenced by a decrease in PLTP mRNA in a variety of tissues. High-density lipoprotein levels decreased in mice fed the atherogenic diet, but there was a proportionally greater decrease in transgenic animals than in controls. After 18 weeks on the atherogenic diet, the transgenic animals had high-density lipoprotein-cholesterol and PLTP activity approximately one-half of that of control animals. Non-denaturing gradient gel electrophoresis of plasma indicated that the atherogenic diet decreased the high-density lipoprotein size distribution in control mice. However, high-density lipoprotein particle size distribution of the transgenic mice was shifted to smaller particles compared with control animals (P < 0.001). These findings suggest that PLTP activity can modulate the effects of an atherogenic diet on high-density lipoproteins.     

Relations between open-field, elevated plus-maze, and emergence tests in C57BL/6JIco and BALB/cAnN@Ico mice injected with ethanol

The effects of ethanol were examined on three tests of exploratory activity in two mouse strains. Although ethanol reduced open-field rearing in both strains, it increased ambulation only in the less active BALB/cAnN@Ico strain, not in the C57BL/6JIco strain. Likewise, ethanol increased open and enclosed arm entries in the elevated plus-maze only in the more anxious BALB/cAnN@Ico strain. However, both strains injected with ethanol emerged faster than placebo from a small chamber at doses not affecting behaviors in the other two tests. Significant correlations were found between emergence latencies on one hand and either slow stereotyped movements or open and enclosed arm entries on the other. The strain-specific effects may be attributable to differences in GABA(A) -related receptor binding or catalase activity.     

Long-term sequelae of HFE deletion in C57BL/6 x 129/O1a mice,an animal model for hereditary haemochromatosis

BACKGROUND: HFE knockout mice (C57BL/6 x 129/Ola strain) mimic the functional aberrations of human hereditary haemochromatosis (HH) in short-term experiments. The present study investigates functional and morphological long-term changes. METHODS: HFE(o/o), HFE(+/o) and HFE(+/+) mice were maintained on iron-rich and control diets for 2 weeks, 3, 12 and 18 months. Light microscopic tissue iron distribution, pathomorphological alterations, tissue iron content and oxidative stress were analysed in liver, pancreas, spleen, gastrointestinal tract, kidneys and myocardium. Additionally, duodenal 59Fe absorption and 59Fe whole body loss were measured. RESULTS: Iron distribution between organs and microscopic iron deposition in the tissues resembled the patterns described in HH. After 3 months of iron-rich feeding duodenal 59Fe absorption decreased to approximately 15% of iron-adequate controls but remained about twice as high in HFE(o/o) as in HFE(+/+) mice. Hepatic iron concentrations reached only half the values known to induce hepatic fibrosis in rats and humans, while whole body 59Fe loss was about twice as high. Consequently no hepatic fibrosis developed, although massive hepatocellular iron deposition and indication for oxidative stress were observed. CONCLUSION: C57BL/6 x 129/O1a HFE(o/o) mice mimic HH iron distribution and the regulation of intestinal iron absorption after long-term feeding. However, characteristic morphological late changes in untreated HH are not modelled.     

Evaluation of eXIA 160XL cardiac‐related enhancement in C57BL/6 and BALB/c mice using micro‐CT

Evaluation of cardiovascular function in mice using micro‐CT requires that a contrast agent be administered to differentiate the blood from the myocardium. eXIA 160XL, an aqueous colloidal poly‐disperse contrast agent with a high iodine concentration (160 mg I ml^?1), creates strong contrast between blood and tissue with a low injection volume. In this study, the blood‐pool enhancement time‐course of eXIA 160XL is monitored over a 48 h period to determine its optimal use during cardiac function studies in C57BL/6 and BALB/c mice. Eight‐second scans were performed (80 kV_p, 110 mA) using the GE Locus Ultra micro‐CT scanner. Six C57BL/6 and six BALB/c male mice (22–24 g) were injected via tail vein with 5 µl g^?1 body weight eXIA 160XL. A precontrast scan was performed; following injection, mice were scanned at 5, 15, 30, 45 and 60 min, and 2, 4, 8, 12, 24 and 48 h. Images were reconstructed, and enhancement–time curves were generated for each of the following tissues: left ventricle (LV), myocardium, liver, spleen, renal cortex, bladder and brown adipose tissue. The highest contrast in the LV occurred at 5 min in both strains (~670 HU above precontrast value). Uptake of the contrast agent by the myocardium was also observed: myocardial tissue showed increasing enhancement over a 4 h period in both strains, remaining even once the contrast was eliminated from the vasculature. In both C57BL/6 and BALB/c strains, eXIA 160XL provided high contrast between blood and myocardial tissue for a period of 30 min following injection. Notably, this contrast agent was also taken up by the myocardium and provided continued enhancement when it was eliminated from the blood, making LV wall motion studies possible. In conclusion, eXIA 160XL, with its high iodine concentration and targeted tissue uptake characteristics, is an ideal agent to use when evaluating cardiovascular function in mice. Copyright © 2012 John Wiley & Sons, Ltd.     

Pre-germinated brown rice prevents high-fat diet induced hyperglycemia through elevated insulin secretion and glucose metabolism pathway in C57BL/6J strain mice

This study investigated the effect and mechanism of pre-germinated brown rice (PGBR) prevented hyperglycemia in C57BL/6J mice fed high-fat-diet (HFD). Normal six-week-old mice were randomly divided into three groups. Group 1 was fed standard-regular-diet (SRD) and group 2 was fed HFD for 16 weeks. In group 3, the mice were fed a HFD with its carbohydrate replaced with PGBR for 16 weeks. Comparing the SRD and HFD groups, we found the HFD group had higher blood pressure, higher concentrations of blood glucose and HbA1c. The HFD group had less protein expression of insulin receptor (IR), insulin receptor substrate-1 (IRS-1), phosphatidylinositol-3-kinase (PI3K), glucose transporter-4 (GLUT-4) and glucokinase (GCK) and greater expression of glucogen synthase kinase (GSK) in skeletal muscle. The HFD group also had less expression of IR, serine/threonine kinase PI3K-linked protein kinase B (Akt/PKB), AMP-activated protein kinase (AMPK), GCK and peroxisome proliferator-activated receptor γ (PPARγ) in liver. In the HFD + PGBR group, the PGBR could reverse the disorders of blood pressure, blood glucose, HbA1c and increase insulin concentration. PGBR increased the IR, IRS-1, PI3K, Akt, GLUT-1 and GLUT-4 proteins, and ameliorated AMPK, GCK, GSK and PPARγ proteins. Together, PGBR prevented HFD-induced hyperglycemia through improving insulin levels, insulin receptor, glucose transporters and enhancing glucose metabolism.     

Tumor necrosis factor-α small interfering RNA alveolar epithelial cell-targeting nanoparticles reduce lung injury in C57BL/6J mice with sepsis

BackgroundThe role of tumor necrosis factor (TNF)-α small interfering (si)RNA alveolar epithelial cell (AEC)-targeting nanoparticles in lung injury is unclear.MethodsSixty C57BL/6J mice with sepsis were divided into normal, control, sham, 25 mg/kg, 50 mg/kg, and 100 mg/kg siRNA AEC-targeting nanoparticles groups (n = 10 per group). The wet:dry lung weight ratio, and hematoxylin and eosin staining, western blotting, and enzyme-linked immunosorbent assays for inflammatory factors were conducted to compare differences among groups.ResultsThe wet:dry ratio was significantly lower in control and sham groups than other groups. TNF-α siRNA AEC-targeting nanoparticles significantly reduced the number of eosinophils, with significantly lower numbers in the 50 mg/kg group than in 25 mg/kg and 100 mg/kg groups. The nanoparticles also significantly reduced the expression of TNF-α, B-cell lymphoma-2, caspase 3, interleukin (IL)-1β, and IL-6, with TNF-α expression being significantly lower in the 50 mg/kg group than in 25 mg/kg and 100 mg/kg groups.ConclusionTNF-α siRNA AEC-targeting nanoparticles appear to be effective at improving lung injury-related sepsis, and 50 mg/kg may be a preferred dose option for administration.     

Involvement of cytokines in the modulation and progression of renal fibrosis induced by unilateral ureteral obstruction in C57BL/6 mice: effects of thalidomide and dexamethasone

This study investigated the kinetics of cytokines that are involved in the development of interstitial fibrosis in mice that were subjected to UUO, the interstitial type I and III collagen deposition, and the effects of Thalido and Dexa treatment on these parameters. Inbred C57BL/6 mice were divided into the groups: Normal (not submitted surgery), Sham (sham surgery), Control (UUO treated with 0.5% carboxymethyl cellulose), Thalido (UUO treated with 5 mg/kg thalidomide), and Dexa (UUO treated with 1 mg/kg dexamethasone). The treatments began the day before surgery and were administered once daily by gavage for 1, 7, or 14 days. At the end of each treatment period, blood samples were collected for the determination of creatinine, urea, cytokines. The Control group exhibited a increase in creatinine concentration compared with the Normal and Sham groups within the first 24 h after UUO, which remained high until days 7 and 14. The urea concentration was higher on days 7 and 14 in the Control group compared with the Sham group. In the Thalido and Dexa groups, a reduction of serum creatinine concentration was seen on day 14. Treatment with Dexa reduced the serum concentration of urea on day 7. The serum concentrations of cytokines (TNF‐α, IL‐1β, IL‐6, IL‐10 and IL‐17) and chemokines (KC, MIG, bFGF) increased in UUO mice at all of the sampling times. The Dexa and Thalido groups exhibited alterations in the concentrations of these cytokines, suggesting the involvement of anti‐inflammatory and immunomodulatory mechanisms that may have modified the fibrosis framework.     

Effects of clozapine administration on body weight, glucose tolerance, blood glucose concentrations, plasma lipids, and insulin in male C57BL/6 mice: A parallel controlled study

Background: Clozapine has been associated with metabolic adverse events (AEs) (eg, elevated body weight, blood glucose concentrations, cholesterol, triglycerides [TG]), all of which have deleterious effects on health and medication compliance. However, little focus has been directed toward finding a suitable experimental model to study the metabolic AEs associated with clozapine.Objective: The aim of this study was to assess the effects of clozapine administration for 28 days on body weight, glucose tolerance, blood glucose concentrations, plasma lipids, and insulin in C57BL/6 mice.Methods: C57BL/6 mice were grouped and treated with clozapine 2 or 10 mg/kg or vehicle intraperitoneally QD for 28 days. Body weight was assessed on days 0 (baseline), 7, 14, 21, and 28, and glucose tolerance, blood glucose concentrations, insulin (calculated by insulin resistance index [IRI]), and plasma lipids (including total cholesterol, TG, high-density lipoprotein cholesterol [HDL-C], and low-density lipoprotein cholesterol) were assessed on day 29.Results: Sixty 10-week-old, male C57BL/6 mice were included in the study and were divided into 3 groups (20 mice per group). The body weight significantly decreased in the clozapine 10-mg-treated group on days 14, 21, and 28 compared with the vehicle group (mean [SD] body weight: 21.61 [1.05] vs 22.79 [1.11], 22.53 [1.05] vs 24.17 [1.24], and 22.21 [1.07] vs 24.99 [1.39] g, respectively; all, P < 0.05). In the clozapine 10-mg/kg group, blood glucose concentrations significantly increased 0, 30, 60, and 120 minutes after glucose administration compared with the vehicle group (mean [SD]: 6.67 [1.25], 25.34 [5.85], 12.68 [3.39], and 7.52 [1.45] mmol/L, respectively, vs 4.61 [0.78], 21.54 [6.55], 11.46 [3.46], and 6.55 [1.42] mmol/L, respectively; all P < 0.05). The clozapine 10-mg/kg group also had significant increases in plasma insulin concentrations compared with the vehicle group (12.70 [5.27] vs 7.62 [4.54] μIU/mL; P < 0.05) and IRI (3.01 [1.26] vs 1.51 [0.96]; P < 0.05). Plasma HDL-C concentration also significantly decreased in the clozapine 10-mg/kg group compared with the vehicle group (1.23 [0.25] vs 1.47 [0.16]; P < 0.05).Conclusion: Clozapine 10 mg/kg was associated with significant decreases in body weight and significant increases in fasting blood glucose and glucose tolerance in these male C57BL/6 mice.