Pbx1基因突变对小鼠脊柱形态的影响

目的：研究Pbx1基因突变对小鼠脊柱形态的影响。方法构建含有Pbx1基因突变的载体,通过微注射注入C57BL/6J小鼠胚泡中,获得的嵌合体小鼠中再筛选稳定含有Pbx1突变的生殖细胞,再培育成含有Pbx1突变的成鼠。成年小鼠的骨架用茜素红染色法染色并拍照。妊娠晚期的小鼠胚胎进行软骨阿尔新蓝染色,并拍照。利用Fisher精确概率法检验Pbx1突变对脊柱骨骼数量的影响。结果 Pbx1-/-小鼠与其同窝的Pbx1+/+野生型小鼠比较,中轴骨骼形态有更多的异常(P<0．001),95.0%的Pbx1-/-小鼠呈现出第6腰椎缺失,所有骶椎呈现融合, Pbx1+/-小鼠的表型介于Pbx1-/-和Pbx1+/+野生型小鼠之间。检查Pbx1-/-小鼠的胸椎,显示脊椎背表面第10至第12胸椎的裂缝发生率为66.7%明显高于野生型小鼠的6.7%(P<0．001)。在小鼠胚胎中,Pbx1+/-和Pbx1-/-小鼠表现为后骶椎骨缺失。结论 Pbx1基因影响小鼠脊柱的发育,对维持脊柱骨正常形态具有重要作用。     

高果糖喂养致小鼠脂肪肝与肝脏氧化应激的时程变化

目的：观察高果糖饮食诱导的小鼠脂肪肝和肝脏氧化应激的发生时程变化,并探讨高果糖饮食致小鼠脂肪肝与氧化应激的关系。方法60只雄性C57BL/J6小鼠随机分为对照组、高果糖组,分别在喂养3 d、8周后测定小鼠空腹血糖( FBG)、空腹血清胰岛素( FINS)及肝脏甘油三酯( TG)含量,并测定各组小鼠肝脏氧化应激相关指标即丙二醛( MDA)、超氧化物歧化酶( SOD)、谷胱甘肽过氧化物酶( GSH-Px)及过氧化氢酶( CAT)水平的变化。结果喂养3 d后,与对照组相比,高果糖组小鼠的FBG、FINS无明显变化( P>0．05),而肝脏TG显著增加( P<0．01);喂养8周后,与对照组相比,高果糖组FBG、FINS、TG均显著增加( P<0．01);喂养3 d后,与对照组相比,高果糖组的MDA、SOD、GSH-Px以及CAT水平均无明显变化(P>0．05);喂养8周后,高果糖组的肝内MDA明显增加(P<0．01),SOD、GSH-Px及CAT活性均显著降低(P<0．01)。结论短期和长期高果糖喂养均可引起肝内脂质沉积,但短期高果糖喂养引起的肝脏脂质沉积不伴有氧化应激;长期高果糖喂养引起的肝脏脂质沉积伴有氧化应激,提示氧化应激与高果糖饮食诱导的脂肪肝发生发展有关,但介导机制有待进一步研究。     

双氢青蒿素对小鼠Lewis肺癌移植瘤生长的影响

目的：探讨双氢青蒿素对小鼠Lewis肺癌移植瘤的抑瘤效应及其作用机制。方法：50只C57BL/6J小鼠皮下接种3LL细胞（2×10^6）,随机分为5组,分别为生理盐水组,阳性对照顺铂组,双氢青蒿素高、中、低剂量组（150、100、50mg/kg）,检测各组小鼠的体重变化和抑瘤率,应用流式细胞术进行瘤细胞的DNA倍体分析。结果：双氢青蒿素中、高剂量组体重无生理盐水组增加明显,其抑瘤率分别为53.50%及59.24%;流式细胞术检测双氢青蒿素能诱导肿瘤细胞凋亡,并能影响肿瘤的细胞周期,G0/G期及G2/M期细胞数大量减少,细胞被阻滞在S1期。结论：口服双氢青蒿素对Lewis小鼠肺癌有明显的抑制作用,可促进肿瘤细胞凋亡。     

墨旱莲对高脂喂养小鼠调血脂作用的影响

摘 要 目的：研究墨旱莲对高脂喂养C57BL/6J小鼠调血脂作用的影响。 方法: 选取60只雌性C57BL/6J小鼠,按体质量分为正常对照组、模型组和墨旱莲低（40 mg·kg-1）、中（120 mg·kg-1）、高（360 mg·kg-1）剂量组,每组12只。对照组和模型组分别喂饲基础饲料和高脂饲料并给予1.0%羧甲基纤维素钠溶液灌胃,给药组在喂饲高脂饲料的同时给予1.0%羧甲基纤维素钠溶液溶解的墨旱莲颗粒灌胃,1次/d,连续6周。在第2周和第6周分别测定小鼠体质量、体长、Lee’s指数和体质指数（BMI）;第6周测定小鼠血清丙氨酸氨基转移酶（ALT）、天门冬氨酸氨基转移酶（AST）、葡萄糖（GLU）、总胆固醇（TC）、三酰甘油（TG）含量,于相同部位取肝脏、腹部及肾周脂肪,称质量并计算脏体比及脂体比,解剖分离小鼠的肝脏,制作HE切片。 结果: 给药2周后,模型组与各给药组小鼠体质量、体长、Lee’s指数、BMI值差异无统计学意义（P>0.05）;给药6周后,各给药组小鼠的体质量、Lee’s指数、BMI、脂肪质量、脂体比、TC、TG均显著低于模型组（P＜0.05）,各给药组小鼠的体长、肝质量、肝体比、ALT、AST、GLU与模型组相比均无统计学意义（P>0.05）。模型组可见小鼠肝脏HE切片中有大量脂肪空泡,而高剂量给药组肝细胞脂肪变性明显减少。 结论: 墨旱莲对高脂喂养C57BL/6J小鼠有明显的降血脂作用。     

葡聚糖硫酸钠诱导不同性别溃疡性结肠炎小鼠模型的比较

目的:探讨性别差异对小鼠溃疡性结肠炎(UC)模型成模的影响,为实验造模提供参考依据.方法:将24只C57BL/6J小鼠根据性别随机分为4组,雌性对照组、雄性对照组、雌性DSS组和雄性DSS组,每组6只,对照组正常饮食,雌性或雄性DSS组给予正常饮食+3％葡聚糖硫酸钠(DSS)溶液自由饮用7?d进行造模.每日记录各组小鼠...     

IL-17抗体对DSS诱导小鼠溃疡性结肠炎的影响

目的 探讨腹腔内注射白介素-17A(IL-17A)抗体与IL-17F抗体对葡聚糖硫酸钠(DSS)诱导的溃疡性结肠炎(UC)小鼠的影响.方法 48只小鼠,随机分为正常对照组、模型组、抗IL-17A组、抗IL-17F组,每组12只.除正常对照组外,其余3组小鼠均饲以DSS溶液.抗IL-17A组和抗IL-17F组于实验第2、...     

H102对APP转基因小鼠突触相关蛋白表达的影响

目的:观察H102对APP转基因小鼠脑内超微结构-突触后致密区(PSD-95)和突触素表达的影响.方法:将16只APP转基因小鼠随机分为模型组和给药组,每组8只.并设同月龄同背景C57BL/6J小鼠为正常组.给药组侧脑室注射H102生理盐水溶液,正常组和模型组侧脑室注射等体积生理盐水,3 μL/d,注射30 d后行行为学检测即水迷宫测试,然后取出并固定脑组织,利用免疫组化及Western blot方法测定小鼠脑组织突触素、PSD-95及shank1的表达.结果:定位航行实验给药组APP转基因小鼠逃避潜伏期从第2天较模型组差异有统计学意义(P<0.05),较正常组从第3天差异无统计学意义(P>0.05);空间探索实验第三象限停留时间和跨越平台次数较模型组差异有统计学意义(P<0.05),较正常组差异无统计学意义(P>0.05).模型组皮质和海马出现突触紊、PSD-95及shank1表达减少;注射H102后突触素、PSD-95及shank1表达较正常对照组差异无统计学意义(P>0.05).结论:H102对阿尔茨海默病(AD)治疗有一定的应用价值.     

异长春花碱脂质体的制备及其在小鼠体内的组织分布

目的:制备异长春花碱(VRB)脂质体并考察其在小鼠体内的组织分布情况。方法:采用薄膜分散法制备VRB脂质体;以Lewis肺癌C57BL/6J荷瘤小鼠为模型,分为对照组(VRB注射液)和脂质体组(VRB脂质体),每组24只,分别尾静脉注射10mg·kg-1,于给药后0.5、2.0、12.0h取样,以高效液相色谱法测定各组小鼠不同时间血浆、心、肝、脾、肺、肾、肌肉、大脑、肿瘤中的药物浓度,并计算制剂的靶向性参数。结果:制备的VRB脂质体的平均粒径为158.3nm,脂质体外观圆整、大小均匀,可见明显的双分子层结构;与VRB注射液比较,VRB脂质体在模型小鼠肝、脾、肿瘤中3个时间点的分布均明显增强(P<0.05或P<0.01),其余组织分布无明显变化;VRB脂质体对模型小鼠具有明显的肝、脾、肿瘤靶向性及一定的肺靶向性。结论:所制备的VRB脂质体对肺癌模型小鼠肿瘤组织具有明显靶向性。     

溴氰菊酯对雄性C57BL/6J小鼠的急性毒作用研究CSCD

溴氰菊酯(deltamethrin,DM)是继有机磷和氨基甲酸酯之后快速发展起来的Ⅱ型拟除虫菊酯类农药,有高效、广谱、低毒和生物降解等特点,在农林业和住宅害虫防治(驱蚊剂)应用广泛。然而,环境与农产品DM残留与环境健康问题与日俱增,对环境暴露人群健康和食品安全造成潜在的危险^([1])。     

Voluntary ethanol drinking in C57BL/6J and DBA/2J mice before and after sensitization to the locomotor stimulant effects of ethanol

RATIONALE: Drug-induced sensitization has been associated with enhanced drug self-administration and may contribute to drug addiction. OBJECTIVES: We investigated the possible association between sensitization to the locomotor stimulant effects of ethanol (EtOH) and voluntary EtOH consumption. METHODS: Mice of the EtOH-avoiding DBA/2J (D2) and EtOH-preferring C57BL/6J (B6) inbred strains were offered the choice of an EtOH solution versus tap water (EtOH-experienced) or just water (Na), and voluntary consumption was measured. Mice from each condition then received repeated EtOH or saline injections, and locomotor responses were measured. Subsequently, all mice were offered the choice of EtOH versus water, and voluntary consumption was again measured. A subsequent study examined relative susceptibility of D2 and B6 mice to EtOH-induced locomotor sensitization. RESULTS: Voluntary EtOH consumption induced locomotor sensitization to an EtOH challenge in B6 mice. D2 mice consumed little EtOH, but developed sensitization with repeated EtOH treatments as expected. EtOH consumption was not altered in EtOH-sensitized D2 mice. Unexpectedly, B6 mice developed significant sensitization, and following sensitization, the EtOH-experienced EtOH-sensitized group consumed more EtOH than their EtOH-experienced salinetreated (non-sensitized) counterparts. In an independent study, B6 mice required between three and five EtOH injections to express sensitization, whereas for D2 mice, between one and three EtOH exposures were sufficient. CONCLUSIONS: Development of sensitization to the locomotor stimulant effects of EtOH may be associated with increased EtOH consumption in mice with high initial avidity for EtOH. In the same mice, voluntary EtOH consumption can also produce behavioral sensitization to the effects of EtOH.     

Alteration of voluntary ethanol and saccharin consumption by the neurosteroid allopregnanolone in mice

RATIONALE: The neurosteroid 3 alpha-hydroxy-5 alpha-pregnan-20-one (allopregnanolone, ALLOP) is a positive modulator of gamma-aminobutyric acid type A (GABA(A)) receptors. Recent findings indicate that ethanol (EtOH) and ALLOP share common mechanisms of action and that ALLOP may modulate some of EtOH's abuse-related effects. OBJECTIVES: The present studies investigated whether ALLOP pretreatment altered voluntary EtOH consumption in male and female C57BL/6J mice, and voluntary saccharin and quinine consumption in male C57BL/6J mice. METHODS: Mice had access to two drinking tubes containing water versus 5% or 10% (v/v) EtOH or a tastant for 2 h each day at the beginning of the dark cycle. Following establishment of stable consumption, animals received 2 days of vehicle followed by 3 days of ALLOP injections (0, 3.2, 10, or 17 mg/kg, IP), immediately prior to EtOH or tastant access. RESULTS: Prior to injection, the 2-h baseline dose of the 10% EtOH solution consumed was 1.31 g/kg (expt 1) or 2.46 g/kg (expt 3) for male and 2.21 g/kg (expt 2) for female mice. Baseline intake of the 5% EtOH solution was 0.60 g/kg for males and 0.75 g/kg for females (expt 5). In males, ALLOP administration significantly and dose-dependently increased consumption of both EtOH solutions during the first hour of availability without affecting water intake. In females, ALLOP did not significantly alter EtOH consumption. Lastly, ALLOP significantly increased saccharin, but not quinine, consumption in males (females were not tested). CONCLUSIONS: ALLOP may increase voluntary EtOH consumption in male mice by altering its reinforcing effects. The lack of significant effect on quinine and water consumption suggests that ALLOP does not simply increase consumption of all fluids.     

Effect of the 5-HT3 antagonist ondansetron on voluntary ethanol intake in rats and mice maintained on a limited access procedure

The effect of the 5-HT₃ antagonist ondansetron on ethanol self-administration was examined in a limited access paradigm. Acute administration of ondansetron (0.01 and 0.1 mg/kg) reduced ethanol intake in male Wistar rats by 35%, whilst water intake was unaffected. Both a lower (0.001 mg/kg) and higher dose (1 mg/kg) of ondansetron failed to modify ethanol consumption. Ondansetron did not, however, alter the pharamacokinetic profile of an orally administered dose of ethanol (1 g/kg) over the same dose range. To examine the generality of these findings and to determine if tolerance would develop to the suppressant effects of ondansetron on ethanol intake, male C57BL/6 mice were treated with ondansetron (0.001, 0.01 and 0.1 mg/kg) over 22 days, 30 min prior to scheduled access to ethanol. Both 0.01 and 0.1 mg/kg doses reduced ethanol intake; however, water intake was not altered by either dose. This finding confirms and extends the generality of the effects of 5-HT₃ receptor antagonists on ethanol intake across different species and different paradigms of ethanol consumption. More importantly, the present study shows that the reduction in ethanol intake induced by ondansetron was maintained even after a prolonged period of treatment and is not due to an alteration in the absorption or metabolism of ethanol.     

Effects of naloxone on ethanol induced alterations of locomotor activity in C57BL/6 mice

Ethanol (2 g or 3 g/kg) or water vehicle was injected intraperitoneally into C57BL/6 mice 15 min after injections of naloxone, a narcotic analgesic antagonist, or its saline vehicle. Locomotor activity was monitored for 60 min beginning 30 min (Experiment 1) or immediately (Experiment 2) following the ethanol injection. In both experiments, animals injected with the lower dose of ethanol were more active than controls during the second half of the activity test. Animals injected with the high dose of ethanol were less active than controls during the first half of the activity test but returned to control levels or above during the second half of the test. Naloxone at the doses used injected 45 min prior to the activity test (Experiment 1) did not alter locomotor activity and did not influence ethanol induced activity changes. When injected 15 min prior to testing (Experiment 2), however, naloxone alone produced a transient reduction in activity observed only during the first half of testing. During the second half of testing all animals injected with naloxone had activity levels similar to controls and lower than those of animals injected with ethanol in the absence of naloxone. Hence, it appears that naloxone at a dose and time period which does not alter the locomotor activity of mice is capable of blocking ethanol induced excitatory effects.     

A procedure to produce high alcohol intake in mice

Rationale While prolonged access to ethanol (EtOH), or deprivations, or their combination have occasionally been shown to yield high levels of voluntary self-administration, in almost all cases, rodents do not self-administer alcohol to the degree that they will develop substantial, intoxicating blood alcohol levels and then continue to self-administer at these levels.Objectives The purpose of the present series of experiments was to modify a fluid restriction procedure to demonstrate consistent, high EtOH consumption.Methods Male and female mice from an alcohol preferring inbred strain (C57BL/6J; B6) as well as from a genetically heterogeneous strain (WSC) were given varying periods of access to fluid, ranging from 90 min to 10 h per day, for 12–21 days. Every 3rd or 4th day, separate groups of mice were offered a 5, 7 or 10% EtOH solution for either 10 min or 30 min, followed by water for the remainder of the time.Results In all studies, stable high EtOH doses were consumed by both B6 and WSC mice across the EtOH sessions, exceeding 2 g/kg in a 30-min session. Mean blood EtOH concentration exceeded 1 mg/ml (i.e. 100 mg%), with values in individual animals ranging from 0.6 mg/ml to 3.4 mg/ml. Notably, mice receiving 10 h of fluid/day continued to consume 2 g/kg doses of EtOH. While this procedure did not produce subsequent preference for EtOH in WSC mice, consumption remained high in some animals.Conclusions These data indicate that scheduling fluid intake produces high, stable EtOH consumption and BEC in male and female B6 and WSC mice.     

Acute anorectic effect of single and combined drugs in mice using a non-deprivation protocol

RATIONALE: Studies of the effect of anorectic drugs such as fenfluramine in mice have indicated the desirability of using experimental protocols that do not involve deprivation. OBJECTIVE: We have developed a non-deprivation or "dessert" protocol for use in mice that are maintained in standard housing conditions, and examine the effects of a serotonergic agent dexfenfluramine (DFEN), a dopaminergic agent phentermine (PHEN), and a selective norepinephrine uptake inhibitor thionisoxetine (TNIX) alone and in combination. METHODS: Female C57BL/6J mice were adapted to 30 min daily presentation of a gelatinized form of sweetened milk using a holder that hooks over the side of the cage during tests; food spillage and contamination are minimal. Dose-inhibition curves were determined for DFEN, PHEN, and TNIX alone and for fixed ratio combinations of DFEN with either PHEN or TNIX. RESULTS: Each drug produced a near linear dose-inhibition curve with the 50% inhibitory doses (DI50) of 5.6, 3.2 and 12.2 mg/kg, respectively. By isobolographic analysis, the effects of the drug combinations were strictly additive. CONCLUSION: The procedure described is highly suitable for testing anorectic drugs in mice and is adaptable to a variety of housing conditions and diets. The DFEN+ PHEN combination was additive, which contrasts with its reported supra-additive effect in rats.     

Cadmium‐induced microsatellite instability in the kidneys and leukocytes of C57BL/6J mice

Cadmium is a cytotoxic, carcinogenic, and mutagenic industrial product or byproduct. The correlation between metal exposure and microsatellite instability (MSI) has been reported by several groups. In the present study, 50 C57BL/6J mice at 6 weeks of age were divided into five groups and intraperitoneally injected with 0, 0.25, 0.5, 1, or 2 mg/kg cadmium chloride quaque die alterna for 4 weeks. Then, the liver, kidney, testis, leukocytes, bone marrow, and small intestine were collected from the treated mice and weighed. Portions of these tissues were fixed for further histological analysis, and the remaining tissues were subjected to genomic DNA extraction for the analysis of a panel of 42 microsatellite markers. The liver and testis weight coefficients were significantly changed in the 1 and 2 mg/kg cadmium chloride‐treated groups compared with the control group. Simultaneously, severe histopathologic changes in the liver and kidneys, along with a complete disorganization of testicular structure and obvious severe necrosis in the testes were observed in the cadmium‐treated group. The cadmium accumulated in the liver and kidneys of the mice in all cadmium‐treated groups; the tissue cadmium concentrations were significantly higher than those in the control group. After STR scanning, MSI was found at three loci (D15Mit5, D10Mit266, and DxMit172) in the kidneys and leukocytes of mice in the lower dose groups (0.25 and 0.5 mg/kg). In summary, we have successfully established a sub‐chronic cadmium exposure model and confirmed that cadmium exposure can induce MSI in mice. We also identified two loci that could be regarded as “hotspots” of microsatellite mutation in mice. © 2014 Wiley Periodicals, Inc. Environ Toxicol 30: 683–692, 2015.     

Dietary administration of diquat for 13 weeks does not result in a loss of dopaminergic neurons in the substantia nigra of C57BL/6J mice

Male and female C57BL/6J mice were administered diquat dibromide (DQ∙Br₂) in their diets at concentrations of 0 (control), 12.5 and 62.5 ppm for 13 weeks to assess the potential effects of DQ on the nigrostriatal dopaminergic system. Achieved dose levels at 62.5 ppm were 6.4 and 7.6 mg DQ (ion)/kg bw/day for males and females, respectively. A separate group of mice was administered 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) ip as a positive control. The comparative effects of DQ and MPTP on the substantia nigra pars compacta (SNpc) and/or striatum were assessed using neurochemical, neuropathological and stereological endpoints. Morphological and stereological assessments were performed by investigators who were “blinded” to dose group. DQ had no effect on striatal dopamine concentration or dopamine turnover. There was no evidence of neuronal degeneration, astrocytic or microglial activation, or a reduction in the number of tyrosine hydroxylase positive (TH⁺) neurons in the SNpc or neuronal processes in the striatum of DQ-treated mice. These results are consistent with the rapid clearance of DQ from the brain following a single dose of radiolabeled DQ. In contrast, MPTP-treated mice exhibited decreased striatal dopamine concentration, reduced numbers of TH⁺ neurons in the SNpc, and neuropathological changes, including neuronal necrosis, as well as astrocytic and microglial activation in the striatum and SNpc.     

Phenobarbital during pregnancy alters operant behavior of offspring in C57BL/6J mice.

Offspring of C57BL/6J injected daily with phenobarbital for the last third of pregnancy responded less than control animals when maintained on various fixed ratio schedules of reinforcement. The response decrement became more pronounced as the schedule demands were increased and was noted in offspring of both sexes. The higest dose (80 mg/kg) was less effective than the 2 lower doses (20 mg and 40 mg/kg) in producing the decrement which may reflect a selection factor due to high neonatal mortality previously reported at this dose. The study provides no evidence of the mechanism mediating the long term behavioral abnormality but does clearly extend the finding of such changes to doses which do not produce increased neonatal mortality or noticeable morphological changes.     

不同品系小鼠肥胖模型比较及C57BL/6J小鼠肥胖机制研究

目的建立和比较不同品系小鼠肥胖模型,并研究C57BL/6J小鼠肥胖形成的分子机制。方法选用C57BL/6J、ICR和KM 3个品系♂小鼠,各品系小鼠随机分为正常对照和高脂模型组,分别在饲养4周与8周后测定小鼠体重、脂肪重量、Lee’s指数;脂肪细胞形态学观察和横截面面积计量;酶法检测血脂和LPL活性,应用荧光实时定量PCR技术探讨模型形成分子机制。结果 C57BL/6J小鼠模型组体重、脂肪重量、Lee’s指数、脂肪细胞横截面面积与对照组比较均明显升高,形成良好肥胖模型,而ICR和KM小鼠肥胖指标不如C57BL/6J小鼠变化明显。机制研究表明,C57BL/6J小鼠造模后血清LPL活性升高,肝脏PPARα、脂肪组织PPARγ和DGAT表达上调,脂肪组织HSL、ATGL和TGH表达下调,这些酶、受体的表达变化是形成肥胖的重要机制。结论 C57BL/6J小鼠经高脂饲料诱导4周后可形成良好肥胖模型,PPARα、PPARγ、LPL、DGAT、HSL、ATGL和TGH既是肥胖形成的主要机制,也是减肥药物作用靶点判断的生物标志物。