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])。     

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。     

姜黄素通过调节组织蛋白酶K改善高脂诱导C57BL/6J小鼠骨结构和骨质量的实验研究

目的探讨姜黄素对高脂诱导的C57BL/6J小鼠骨结构和骨质量的影响及其与组织蛋白酶K(cathepsin K)表达的相关性。方法用姜黄素(50 mg·kg~(-1))干预高脂饲料诱导的C57BL/6J小鼠骨质疏松模型12周后,取小鼠股骨和胫骨,分别用HE染色、茜素红染色和番红O/固绿染色观察骨组织微结构变化、骨代谢以及骨发育情况;用免疫组化法和Western blot法检测小鼠骨组织中组织蛋白酶K蛋白的表达。结果病理形态学结果显示,姜黄素能明显改善高脂诱导的C57BL/6J小鼠的骨组织微结构,促进软骨发育和改善骨钙化程度;骨生物力学结果表明,姜黄素能明显提高高脂诱导C57BL/6J小鼠的骨强度;免疫组化和Western blot检测结果显示,姜黄素能够明显抑制小鼠骨组织中的组织蛋白酶K表达。结论姜黄素能提高高脂诱导C57BL/6J小鼠的骨强度,改善骨微结构,其发挥骨保护作用机制之一可能与抑制组织蛋白酶K的表达相关。     

C57/BL6小鼠急性心肌梗死模型制备方法的总结与改良

目的对C57/BL6小鼠急性心肌梗死模型建立方法进行总结和改良,以提高建模可靠性、稳定性及可重复性,减少死亡率。方法40只C57/BL6小鼠,腹腔内注射苯巴比妥钠全身麻醉后气管切开并插管,小动物呼吸机辅助呼吸。常规消毒铺巾后,切开左胸前区皮肤,经左侧第3、4肋间进入胸腔暴露心脏,左前降支冠状动脉结扎造成急性心肌梗死。对围手术期可导致失败和死亡的原因如麻醉、人工辅助呼吸、开胸过程及结扎冠状动脉位置等进行分析和改进。结果成功建立了C57/BL6小鼠急性心肌梗死模型。术后24hC57/BL6小鼠存活率为95%,4周时存活率为92.5%。结论通过方法改进,能快速有效地建立C57/BL6小鼠急性心肌梗死模型,并降低建模过程中C57/BL6小鼠的死亡率。     

(C57BL/6×615)F1代小鼠L615白血病模型的建立

目的　了解 L6 15白血病细胞株能否在 (C5 7BL/ 6× 6 15 ) F1小鼠体内建立白血病模型。方法　雄性 6 15小鼠与雌性 C5 7BL / 6小鼠采用长期同居法培育 (C5 7BL / 6× 6 15 ) F1小鼠 ,6 15、F1小鼠分别经腹腔接种不同数量 L 6 15白血病细胞株 ,观察其白血病发病情况 ;取发病濒死 F1小鼠脾脏 ,制备脾细胞悬液 ,按不同数量经腹腔注射分别接种予 F1小鼠 ,观察白血病发病情况。结果　 (C5 7BL/ 6× 6 15 ) F1小鼠接种 L6 15白血病细胞后 10 0 %发病 ,L6 15白血病细胞可在 (C5 7BL/ 6× 6 15 ) F1小鼠体内传代。结论　 L6 15白血病细胞株能在 (C5 7BL/ 6× 6 15 ) F1小鼠体内成功接种并传代     

建立小鼠2型糖尿病模型时链脲佐菌素剂量的研究

目的：研究链脲佐菌素（STZ）注射剂量对建立2型糖尿病小鼠模型的影响。方法：不同文献中STZ的注射剂量不一致。本文以存活率和成模率两个因素为指标,采用高脂饲料喂养加不同浓度梯度的链脲佐菌素（STZ）注射建立2型糖尿病模型。结果：50mg/Kg剂量组小鼠虽然全部存活,成模率为0;100mg/Kg剂量组全部存活,成模率20%;150mg/Kg剂量组死亡率达70%,但存活下来的30%全部成模;200mg/Kg剂量组的小鼠全部死亡。结论：125mg/Kg是此方法中的STZ最佳剂量。     

Behavioral study of an aging model induced by different doses of D-galactose in C57BL／6J mice

Rodents chronically injected with D-galactose (D-gal have been used as an animal model for brain aging or antiaging pharmacology research. However, the dose of D-gal used to induce behavioral impairment has been reported in a wide range. Besides, very few studies used the C57BL inbred mouse strain to construct this model, which is one of the most     

川芎提取物及复合配方对睾酮诱导脱发的C57BL/6小鼠的治疗效果和机制研究

目的 观察中药川芎提取物和复合配方(含川芎,生姜,侧柏叶,人参,丹参,何首乌)局部外用对C57BL/6雄激素性脱发模型小鼠的治疗效果以及机制初探。方法 采用背部施加睾酮溶液连续21 d的方法诱导C57BL/6小鼠雄激素性脱发模型,肉眼观察涂抹不同浓度川芎提取物及复合配方物后小鼠背部皮肤的颜色变化及毛发的恢复生长情况;测定给药后小鼠新生毛发的长度、覆盖率评价对毛发生长的影响;通过皮肤测试仪测定小鼠皮肤水分、油分和温度变化情况;通过皮肤病理切片观察各组小鼠皮肤厚度,毛囊形态、大小等组织学变化;ELISA法检测给药后小鼠皮肤中α-MSN、TGF-β1、VEGF的水平。结果 川芎醇提取物能够促进脱发小鼠的毛发生长,低剂量组效果会优于高剂量组及复合配方组;水分、油分和温度值结果显示模型鼠皮肤的水分减少,油分升高,温度略微升高,而经治疗后,小鼠水分、油分和温度恢复到正常值;组织学结果显示川芎和其复合配方能够增加小鼠皮肤厚度、生长期毛囊的数量;川芎高低剂量和复合配方均能不同程度增加小鼠皮肤α-MSN、TGF-β1、VEGF的含量。结论 中药川芎局部应用可以通过恢复脱发模型小鼠的水分,油分和温度、增加...     

链脲佐菌素诱导1型糖尿病小鼠模型的研究

目的 探讨多次小剂量链脲佐菌素(MLD-STZ)诱导的1型糖尿病小鼠模型特点.方法 腹腔注射40 mg/kg体质量的STZ,每天1次连续5 d,观察小鼠血糖、尿糖及胰岛病理组织学改变.结果 模型制备成功率为65%,与正常对照组相比造模成功小鼠血糖、尿糖明显升高,有明显胰岛炎改变,且血糖自STZ末次注射后第4周至第8周一直维持在较高水平.结论 MLD-STZ腹腔注射能成功诱导1型糖尿病小鼠模型,且该模型血糖稳定时间较长.     

扩增活化的淋巴细胞EAL在C57BL/6小鼠中的重复给药毒性研究

目的 对小鼠重复给予扩增活化的淋巴细胞EAL,考察其毒性反应,为临床应用提供安全性依据。方法 采用C57BL/6小鼠,设A、B两大项目组,每个大项目组均设置阴性对照组、溶媒对照组、低剂量（1.5×10⁶/只）及高剂量（1×10⁷/只）组。A项每组36只,进行常规毒性检测、血清生化测定、血液学测定、外周血T淋巴细胞亚群分布测定、大体病理学及组织病理学检查;B项每组24只,进行免疫学测定,包括γ-干扰素（IFN-γ）水平和外周血T淋巴细胞亚群分布测定。所有组别均雌雄各半,静脉注射给药,每周1次,共17次,恢复期为28 d。结果 重复给予EAL可能会使C57BL/6小鼠体质量和摄食量增加（P<0.05）。IFN-γ检测结果显示给药组动物个别时间点IFN-γ水平升高。组织病理学检查结果显示给予供试品会加重低剂量组、高剂量组动物脾脏生发中心明显及易染体巨噬细胞增多的病变程度和/或病变频度。供试品未对其他评价指标产生明显影响。结论 C57BL/6小鼠重复给予EAL,可能会引起动物体质量、摄食量的增加以及脾脏生发中心明显和易染体巨噬细胞增多,未见其他相关的毒理学反应。该结果为EAL进入临床试验奠定了基础。     

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.     

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.     

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.     

Genetic differences in intravenous cocaine self-administration between C57BL/6J and DBA/2J mice

In experiment 1, two different strains of mice [C57BL/6J (B6) and DBA/2J (D2)] were allowed to nosepoke for 5 µl intravenous (IV) infusions during 2-h daily sessions. Two nosepoke holes were available, only one of which was reinforced on an FR-3 schedule with a 10-s time-out indicated by a light inside the reinforced nosepoke hole. During the first nine sessions, infusions were saline. On subsequent sessions, mice acquired nosepoking for 0.5 mg/kg cocaine. Finally, all mice were extinguished by again receiving only saline infusions. Cocaine acted as a reinforcer in both strains. In experiment 2, different mice from the same two strains were allowed to acquire nosepoking for IV cocaine at one of three unit doses (0.5, 1.0, or 2.0 mg/kg). Although there were no effects of unit dose on rate of acquisition, B6 mice were faster in acquiring self-administration behavior than were D2 mice. Experiment 3 assessed behavior in the same mice, after acquisition had occurred. D2 mice nosepoked at a lower rate at asymptote than did B6 mice, but with a higher preference for the cocaine reinforced hole. Unit doses of cocaine were then manipulated within subjects, from 0.125 to 2.0 mg/kg per infusion. Higher doses yielded lower response rates than lower doses, both between and within subjects. Behavior in D2 mice relative to B6 mice also appeared to be shifted to the left of the dose-response curve measured within-subjects. Together, these findings indicate that although cocaine serves as a reinforcer in both strains, there are genetic differences in the pattern of cocaine self-administration between these two mouse strains.     

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。     

Verticalization of behavior elicited by dopaminergic mobilization is qualitatively different between C57BL/6J and DBA/2J mice

Behavioral effects of dopaminergic stimulation were evaluated in C57BL/6J mice and compared to the effects occurring in DBA/2J mice, an inbred strain with reduced densities of striatal dopamine receptors. Effects of apomorphine (0.5–64 mg/kg) alone and in combination with cocaine (30 mg/kg) were assessed using a time-sampling technique that classified climbing and leaning in separate categories. Locomotion was also assessed in a separate experiment. Climbing occurred in DBA/2J mice only at doses of apomorphine that were 16 times higher than the smallest effective dose in C57BL/6J mice; nevertheless, relative to baseline values, effects were fairly comparable. By contrast, whereas DBA/2J mice showed dose-dependent leaning under apomorphine, C57BL/6J mice exhibited little leaning even at doses not producing climbing, and only after the highest apomorphine dose was leaning significantly increased. Apomorphine was equipotent in inducing gnawing across strains, although somewhat less efficacious in DBA/2J mice. When given alone, cocaine produced significant climbing, but not leaning or gnawing, in either strain. Whereas cocaine potentiated apomorphine-induced climbing and gnawing in both strains, apomorphine-induced leaning was not consistently changed by cocaine in either strain. These effects were not indirectly due to hyperkinesia, since neither apomorphine alone nor apomorphine and cocaine in combination was stimulant; apomorphine alone reduced locomotor activity and attenuated cocaine-induced hyperkinesia. The present data do not support a unitary, purely quantitative, account of insensitivity to dopaminergic stimulation based upon low densities of striatal dopamine receptors in DBA/2J mice. Rather, this constellation of results is suggestive of qualitative interstrain dissimilarities in dopaminergic responsiveness that could reflect organizational differences in receptor populations.The facilities in which the mice were maintained are fully accredited by the American Association for the Accreditation of Laboratory Animal Care (AAALAC), and the studies described here were conducted in accordance with the Guide for Care and Use of Laboratory Animals provided by the NIH and adopted by NIDA.     

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.     

Audiogenic seizures and brain extracts: Enhancement by extracts from C57BL/6J mice subjected to audiogenic priming

Donor C57BL/6J mice were given audiogenic priming (AP) by exposure to noise at 16 days of age (T_o) and sacrified at intervals from 1 hr to 18 days thereafter. Brains from AP and littermate non-AP mice were extracted in 1 M acetic acid, and passed through a filter with a nominal mol. wt. cutoff of 10,000 daltons. The filtrates were lyophilized and resuspended in H₂O (0.1 ml/brain). Recipient C57BL/6J mice were also exposed to 30 sec of 127 ± 2 dBA at 16 days of age, and injected IP with one brain-equivalent of extracts from either AP or non-AP donors immediately thereafter. All recipients were tested for convulsability at 18 days of age. There were no differences in audiogenic convulsion rates between groups given AP or non-AP extracts from donors sacrificed 1 to 4 hr after T_o. Recipient convulsion rates were higher in AP relative to non-AP extract-injected mice when AP donors were sacrificed 1 to 18 days after T_o. The extract taken from donors 1 day after T_o appears more potent than extract taken either before or later.     

Differential responsiveness to cocaine in C57BL/6J and DBA/2J mice

 The present study compared cocaine-induced hyperlocomotion and cocaine IV self-administration in DBA/2J and C57BL/6J mice. In the locomotor activity experiment, these strains were tested for hyperlocomotion after IP cocaine injection (0–60.0 mg/kg), using a Digiscan Animal Activity Monitoring System. In the cocaine IV self-administration experiment, they were compared for their ability to acquire and maintain cocaine self-administration in operant chambers with levers as the manipulanda. Animals were first trained to respond for food as a reinforcer (condensed milk solution); they were then submitted to surgical IV insertion of an indwelling catheter, and required to respond for IV cocaine (0.25–4.0 mg/kg per injection) as a reinforcer. DBA/2J mice showed significantly higher maximal cocaine-induced hyperlocomotion, more rapid acquisition of cocaine self-administration, and significantly lower rates of cocaine self-administration. Cocaine concentration in the brains of DBA/2J and C57BL/6J mice failed to differ following IP injection, suggesting that distribution factors were not involved in the differential responses to cocaine. Although not conclusive, this pattern of effects may suggest that cocaine has greater reinforcing efficacy in DBA/2J mice, confirming genetic make-up as a determinant factor in cocaine taking behavior. Received: 6 October 1997 / Final version: 4 January 1998