Bone marrow suppression is a common side effect of radiotherapy and a major cause of mortality following exposure to medium or high doses of total body irradiation (TBI). In this study, naked mole rats (NMRs) have been demonstrated to exhibit significantly greater tolerance to high-dose TBI than mice. Surviving NMRs maintain red blood cell (RBC) counts and restore the bone marrow microenvironment. A comprehensive single-cell RNA sequencing (scRNA-seq) analysis of NMR bone marrow cells in response identified two TBI-resistant subpopulations of HSPCs (C19 and C24) in NMRs, and C24 increased post-TBI. These subpopulations exhibit unique regulatory mechanisms related to oxidative stress damage, cell cycle regulation, DNA repair, and HSPC proliferation and differentiation. These mechanisms contribute to the enhanced survival of NMRs under high-dose TBI conditions. These findings suggest that NMRs serve as a valuable model for seeking radioprotection mechanisms and potential therapeutic and protective strategies, particularly in the context of long-term or high-dose irradiation therapies.

High doses of radiation can cause irreversible bone marrow hematopoietic damage and even death. No effective strategies have been developed to protect against radiation effects in hematopoietic stem cells (HSCs). A total-body irradiation model was used to determine damage to HSCs. HSCs were sorted for transcriptome sequencing, and gene function analysis showed that Octamer-Binding Transcription Factor 4 (Oct4) increased significantly after irradiation. Oct4 deletion or inhibition of nuclear factor kappa-B (NF-κB) significantly reversed HSC apoptosis, promoted HSC colony formation, reduced cellular DNA damage, and promoted bone marrow regeneration after irradiation. ChIP assays showed that Oct4 binds to the IκB kinase (IKK) promoter region and increases the level of IKK. Overexpression of Oct4 significantly increased the entry of NF-κB into the nucleus after irradiation. NF-κB activators reversed the protective roles of knocking out Oct4. In vivo, the knockout of Oct4 and inhibition of NF-κB significantly improved the survival rate of mice after irradiation. We further found that the expression level of Oct4 decreased significantly in human leukemia cells, while the overexpression of Oct4 significantly increased the level of apoptosis in leukemia cells after irradiation. This study demonstrated a novel role of Oct4 in mediating apoptosis of HSCs after irradiation through the NF-κB pathway, providing an important biomedical strategy for the functional protection of HSCs in bone marrow after irradiation.

Although radiotherapy is the most effective treatment modality for brain tumors, it always injures the central nervous system, leading to potential sequelae such as cognitive dysfunction. Radiation induces molecular, cellular, and functional changes in neuronal and glial cells. The hippocampus plays a critical role in learning and memory; therefore, concerns about radiation-induced injury are widespread. Multiple studies have focused on this complex problem, but the results have not been fully elucidated. Naked mole rat brains were irradiated with 60Co at a dose of 10 Gy. On 7 days, 14 days, and 28 days after irradiation, hippocampi in the control groups were obtained for next-generation sequencing. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were subsequently performed. Venn diagrams revealed 580 differentially expressed genes (DEGs) that were common at different times after irradiation. GO and KEGG analyses revealed that the 580 common DEGs were enriched in molecular transducer activity. In particular, CACNA1B mediated regulatory effects after irradiation. CACNA1B expression increased significantly after irradiation. Downregulation of CACNA1B led to a reduction in apoptosis and reactive oxygen species levels in hippocampal neurons. This was due to the interaction between CACNA1B and Nrf2, which disturbed the normal nuclear localization of Nrf2. In addition, CACNA1B downregulation led to a decrease in the cognitive functions of naked mole rats. These findings reveal the pivotal role of CACNA1B in regulating radiation-induced brain injury and will lead to the development of a novel strategy to prevent brain injury after irradiation.

Objective Mice are routinely utilized as animal models of drug-induced liver injury (DILI), however, there are significant differences in the pathogenesis between mice and humans. This study aimed to compare gene expression between humans and mice in acetaminophen (APAP)-induced liver injury (AILI), and investigate the similarities and differences in biological processes between the two species.Methods A pair of public datasets (GSE218879 and GSE120652) obtained from GEO were analyzed using "Limma" package in R language, and differentially expressed genes (DEGs) were identified, including co-expressed DEGs (co-DEGs) and specific-expressed DEGS (specific-DEGs). Analysis of Gene Set Enrichment Analysis (GSEA), Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed analyses for specific-DEGs and co-DEGs. The co-DEGs were also used to construct transcription factor (TF)-gene network, gene-miRNA interactions network and protein-protein interaction (PPI) network for analyzing hub genes.Results Mouse samples contained 1052 up-regulated genes and 1064 down-regulated genes, while human samples contained 1156 up-regulated genes and 1557 down-regulated genes. After taking the intersection between the DEGs, only 154 co-down-regulated and 89 co-up-regulated DEGs were identified, with a proportion of less than 10%. It was suggested that significant differences in gene expression between mice and humans in drug-induced liver injury. Mouse-specific-DEGs predominantly engaged in processes related to apoptosis and endoplasmic reticulum stress, while human-specific-DEGs were concentrated around catabolic process. Analysis of co-regulated genes reveals showed that they were mainly enriched in biosynthetic and metabolism-related processes. Then a PPI network which contains 189 nodes and 380 edges was constructed from the co-DEGs and two modules were obtained by Mcode. We screened out 10 hub genes by three algorithms of Degree, MCC and MNC, including CYP7A1, LSS, SREBF1, FASN, CD44, SPP1, ITGAV, ANXA5, LGALS3 and PDGFRA. Besides, TFs such as FOXC1, HINFP, NFKB1, miRNAs like mir-744-5p, mir-335-5p, mir-149-3p, mir-218-5p, mir-10a-5p may be the key regulatory factors of hub genes.Conclusions The DEGs of AILI mice models and those of patients were compared, and common biological processes were identified. The signaling pathways and hub genes in co-expression were identified between mice and humans through a series of bioinformatics analyses, which may be more valuable to reveal molecular mechanisms of AILI.

Health and longevity are the dreams of mankind and the main field of the medical community. The naked mole rat (NMR) is a unique murine animal with extremely long lives (exceeding 38 years), revealing little signs of aging such as reproductive decline, neural degenerative diseases, and cancer. They provide us with valuable perspectives on preventing age-related diseases. This review systematically summarized the characters of different systems of naked mole rats in aging resistance, and furtherly exploited the mechanisms for aging resistance form genome, telomeres, protein recycling, metabolism, and oxidative stress attitudes. As a species with a high similarity with human beings, it cannot be ruled out that after reasonable validity, safety and ethical evaluation, the dominant genes of naked mole rats will be developed in medical transformation, to realize the dream of human health and longevity.

目的 建立裸鼹鼠乳鼠心脏成纤维细胞的体外分离、培养及鉴定方法.方法 选取出生1～3 d的裸鼹鼠乳鼠,在冰上分离出乳鼠心脏,用眼科剪将心脏剪成约1 mm×1 mm×1 mm小块,采用胰蛋白酶和Ⅱ型胶原酶先后消化法分离心脏成纤维细胞.在光学显微镜下观察心脏成纤维细胞形态特征变化,CCK-8法检测细胞增殖活性,蛋白质印迹和免疫荧光法检测细胞波形蛋白表达情况.结果 酶消化法分离的心脏成纤维细胞原代培养4 h已经完全贴壁,36 h即可铺满整个35 mm培养皿.传代培养2～3 d时心脏成纤维细胞增殖活力最强,蛋白质印迹和免疫荧光均证实细胞表达波形蛋白.结论 胰蛋白酶和Ⅱ型胶原酶先后消化法分离裸鼹鼠乳鼠心脏成纤维细胞,可获得活力好且纯度高的心脏成纤维细胞.

作为同时具有自然科学和人文科学的一门学科,医学的属性决定了其人文素质教育部分在医学院校中的重要地位.实验动物学因其特有的理论体系及独到的学科特色,在医学院校中的医教研等各个领域发挥着重要的支撑作用.因此,将医学人文素质教育融入实验动物学课程中,有利于培养科学精神与人文精神相统一的高素质医学人才,亦有利于进一步促进和提高实验动物学的学科发展.

药物性肝损伤是临床上最常见的药物不良反应之一,严重可引起急性肝功能衰竭,甚至死亡.临床上,对这类损伤的诊治尚缺乏特异性的诊断和治疗手段.构建相应的动物模型是深入开展机制研究或者筛选有效的诊断、治疗手段的重要支撑条件.目前研究中建立了大量的药物性肝损伤动物模型,其中应用较多的有非甾体类抗炎药、抗菌药、抗癫痫药物、抗甲状腺药物等诱发的肝损伤模型,所选择的动物以小鼠、大鼠居多.本文结合近年来的文献报道,综述了这些类型动物模型的制备方法、成模标准及其特点,以期为相关模型的构建提供参考.

目的 通过选取不同年龄段的裸鼹鼠,比较肝组织在衰老进程中的变化.方法 选取幼年裸鼹鼠(2 年龄)、中年裸鼹鼠(10 年龄)、老年裸鼹鼠(20 年龄),采集血液,分离血清,检测肝功能 4 项.采集肝,测定肝指数.制作石蜡切片,经 HE染色和 Masson染色后,光学显微镜下观察肝组织形态结构.采用动物组织生化检测试剂盒检测肝组织丙二醛(MDA)、总抗氧化能力(T-AOC)和氧化型谷胱甘肽(GSSG)水平.结果 与幼年组裸鼹鼠比较,中年组和老年组裸鼹鼠肝指数、血清天冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)、碱性磷酸酶(ALP)和白蛋白(ALB)水平均无显著差异(P>0.05).HE染色及 Masson染色结果均显示各组裸鼹鼠肝组织结构完整,无病理变化.中年组裸鼹鼠肝组织中的 MDA、T-AOC水平无显著差异(P>0.05),老年组裸鼹鼠肝组织中的 MDA、T-AOC 水平显著升高(P<0.05),两组裸鼹鼠肝组织 GSSG水平均无显著差异(P>0.05).结论 裸鼹鼠肝组织在衰老进程中表现出一定程度的抗衰老能力,具体抗衰老机制有待深一步研究.

在当前高等教育大众化的背景下,高等院校青年教师队伍不断壮大,已经成为高校师资队伍的主要力量.然而,青年教员初为人师,通常缺乏相应的课堂经验与授课技巧,特别是当前多学科融合交叉的大趋势对高校青年教师的任教能力和知识储备提出了更高要求.如何提高青年教师自身任教能力也成为近年来高教界关注的热点之一.文章分析了青年教师在教学中面临的问题,总结了青年教师培训在青年教师成长中的作用,同时对青年教师培训给出了一些思索和建议,对青年教师培训中应该注意的问题进行了探讨,以期为广大青年教师培养和成长提供参考.

Naked mole-rats (NMRs) (Heterocephalus glaber) are highly social and subterranean rodents with large communal colonies in burrows containing low oxygen levels. The inhibition of severe hypoxic conditions is of particular interest to this study. To understand the mechanisms that facilitate neuronal preservation during hypoxia, we investigated the proteins regulating hypoxia tolerance in NMR hippocampal neurons. Caveolin-1 (Cav-1), a transmembrane scaffolding protein, confers prosurvival signalling in the central nervous system. The present study aimed to investigate the role of Cav-1 in hypoxia-induced neuronal injury. Western blotting analysis and immunocytochemistry showed that Cav-1 expression was significantly upregulated in NMR hippocampal neurons under 8% O2 conditions for 8 h. Cav-1 alleviates apoptotic neuronal death from hypoxia. Downregulation of Cav-1 by lentiviral vectors suggested damage to NMR hippocampal neurons under hypoxic conditions in vitro and in vivo. Overexpression of Cav-1 by LV-Cav-1 enhanced hypoxic tolerance of NMR hippocampal neurons in vitro and in vivo. Mechanistically, the levels of hypoxia inducible factor-1α (HIF-1α) are also increased under hypoxic conditions. After inhibiting the binding of HIF-1α to hypoxia response elements in the DNA by echinomycin, Cav-1 levels were downregulated significantly. Furthermore, chromatin immunoprecipitation assays showed the direct role of HIF1α in regulating the expression levels of Cav-1 in NMR hippocampal neurons under hypoxic conditions. These findings suggest that Cav-1 plays a critical role in modulating the apoptosis of NMR hippocampal neurons and warrant further studies targeting Cav-1 to treat hypoxia-associated brain diseases.

实验动物学是医科院校的重要基础课程之一,在生物医学本科生培养中发挥着重要作用.第二课堂作为实验动物学第一课堂的延伸,具有内容丰富、形式多样、针对性强等特点,能够培养学生的科学思维,提高创新能力.文章阐述了实验动物学开展第二课堂的意义和优势,分析了开展第二课堂面临的问题,并进一步提出了医科院校开展实验动物学第二课堂教学的具体措施,以期为广大高校开展实验动物学第二课堂建设提供借鉴和启发.

裸鼹鼠具有抗肿瘤、耐低氧、耐疼痛、寿命长等优势特性,近年来逐渐成为科研界的新星,但是其在神经科学领域的应用尚待进一步深入推广.本文通过对裸鼹鼠脑形态,及大脑结构中控制视觉、听觉、嗅觉、感觉等功能的中枢结构进行系统的描述,系统阐述裸鼹鼠在长期演化过程中对低氧、黑暗等地下环境所做出的的适应性改变.裸鼹鼠这一结构与功能相适应的特征性改变,有望使其成为研究神经系统疾病包括神经退行性病变等方面的优势动物模型,从而进一步推动人类健康医学的发展.

实验动物学是医科院校学生的重要基础课程之一,其蕴含着一定的思想政治教育元素,能够承担和发挥思想政治教育的作用.在当前全面深化“课程思政”的教育改革背景下,深入挖掘实验动物学课程的思政元素与措施具有重要的实践意义.本文基于医科院校学生的专业特点,探讨了实验动物学课程教学中的思政教学案例,并提出了“课程思政”的举措,以期为广大医科院校实验动物学“课程思政”教学改革提供参考.

目的 分离培养裸鼹鼠皮肤成纤维细胞并对其进行鉴定,探讨裸鼹鼠皮肤成纤维细胞是否具有分泌外泌体的能力.方法 无菌取新生裸鼹鼠背部皮肤,剪碎成1～2mm2大小,将组织块平铺于细胞培养皿中,待贴壁后以低糖DMEM(含20％胎牛血清)培养液进行培养,胰酶消化法对传代培养细胞进行纯化;通过细胞免疫荧光、蛋白质印迹法检测波形蛋白表达情况,对成纤维细胞进行鉴定;待细胞生长至融合度约80％时,改换低糖DMEM(含20％去除外泌体的胎牛血清)培养48h后收集上清液,超高速离心法分离外泌体,透射电镜观察形态,纳米流式分析颗粒直径,蛋白质印迹法检测外泌体相关特异性蛋白表达情况,进行外泌体鉴定.结果 新生裸鼹鼠背部皮肤组织块培养30 h后可见少量细胞自组织块游离出,培养5d后可见大量细胞自组织块游离生长,细胞呈细长梭形或不规则多角形,放射状生长.细胞免疫荧光及蛋白质印迹法检测均证实分离细胞表达波形蛋白.超高速离心法离心细胞上清液,透射电镜下可观察到膜状杯托样外泌体,纳米流式分析粒径在46.75～206.75 nm,蛋白质印迹法检测显示其对外泌体特异性蛋白CD63、肿瘤易感基因101(tumor susceptibility gene,TSG101)和热休克蛋白70(heat shock protein 70,Hsp70)具有特异性.结论 分离培养的细胞具有成纤维细胞的形态学特征,并表达成纤维细胞的特征分子波形蛋白.裸鼹鼠皮肤成纤维细胞具有分泌外泌体的能力,为研究裸鼹鼠外泌体所携带的生物活性分子及其生物学功能提供了基础.

目的 观察60Coγ射线辐射后裸鼹鼠肾脏、肺脏和骨骼肌组织形态结构变化和相应组织氧化应激指标变化.方法 裸鼹鼠经全身一次性10 Gy 60Coγ射线辐射,分别于辐射后7d和14d采集裸鼹鼠肾脏、肺脏和腓肠肌,制作石蜡切片,经HE染色后,光学显微镜下观察肾脏、肺脏和骨骼肌形态结构;采用动物组织生化检测试剂盒检测肾脏、肺脏和腓肠肌组织丙二醛(MDA)、总抗氧化能力(T-AOC)、谷胱甘肽(GSH)和氧化型谷胱甘肽(GSSG)等指标.结果 辐射后裸鼹鼠肾脏、肺脏和骨骼肌均无明显病理改变.辐射后肾脏组织中的MDA含量显著升高(P ＜ 0.01),GSH含量先显著升高(P ＜ 0.05),后显著降低(P ＜ 0.05),GSSG和T-AOC未出现显著变化(P ＞ 0.05);肺脏组织MDA含量显著升高(P ＜ 0.05),GSH、GSSG和T-AOC随时间延长先降低后升高(P ＜ 0.05);骨骼肌中MDA的含量显著上升(P ＜ 0.01),而GSH和GSSH的含量随时间的延长先降低后升高(P ＜ 0.01),T-AOC在辐射后7d出现明显下降(P ＜0.01),14 d时仍然维持7d水平.结论 裸鼹鼠肾脏、肺脏和骨骼肌在高剂量60Coγ射线辐射后表现出一定程度的耐受能力,具体耐受机制有待深入研究.

在统计《实验动物科学》2007-2019年刊载的78期1477篇论文有关数据的基础上,对刊发论文基本情况(包括载文量,基金项目论文,论文的作者、单位分布、地区分布、合作度和合著率等)和论文内容(研究方向和研究热点)进行定量分析,以期探索本刊在实验动物学科发展中的作用,了解和把握学科发展趋势,为科技工作者搭建更好的学术交流与对话平台提供参考.

目的 观察60Coγ射线辐射后裸鼹鼠脾脏免疫系统及组织生物化学指标的变化,初步了解裸鼹鼠脾脏辐射耐受特性.方法 用辐照剂量率为1.163 Gy/min,总剂量为10 Gy的60Coγ射线对裸鼹鼠全身一次性辐射.采集正常对照及辐照后7 d、14 d和21 d的裸鼹鼠脾脏,流式细胞术检测脾脏B淋巴细胞和巨噬细胞比例.采用动物组织生化检测试剂盒检测脾脏组织丙二醛(MDA)、总抗氧化能力(T-AOC)、谷胱甘肽(GSH)和氧化型谷胱甘肽(GSSG)等指标.结果 流式细胞术检测结果显示,辐照后B淋巴细胞比例及巨噬细胞比例均明显升高(P ＜ 0.01).生化检测结果显示,辐照后脾脏MDA水平明显升高(P ＜ 0.05);GSH和GSSH逐渐明显降低(P ＜ 0.05);辐照后T-AOC水平明显降低(P ＜ 0.01),但辐照后21 d有所上升,明显高于辐照后7d和14d(均P ＜ 0.01).结论 裸鼹鼠脾脏对60Coγ射线具有一定程度的耐受能力,但其耐受机制尚未明确.

目的 建立一种裸鼹鼠海马神经元的纯化培养方法,并初步探讨其低氧耐受特性.方法 收集妊娠60～65 d裸鼹鼠胚胎海马组织内的细胞,利用含有Neurobasal+2％B27+10 μtmol/L5-氟尿嘧啶的培养基进行神经元纯化,海马神经元维持培养基为含有体积分数2％B27的Neurobasal培养基.体外贴壁培养6～7d,采用倒置显微镜观察细胞的生长状态,利用神经元特异核蛋白(NeuN)抗体进行鉴定.利用CCK8试剂盒进行海马神经元低氧耐受功能的研究(低氧浓度为8％).利用QPCR检测海马神经元中缺氧诱导因子-1α(HIF-1α)在低氧情况下的表达水平.结果 通过本方法获得的海马神经元具有典型的神经元形态特征,免疫细胞化学染色显示纯化所得的细胞均呈NeuN阳性,低氧条件下细胞存活率、轴突长度显著大于常氧情况下的数值,低氧情况下裸鼹鼠海马神经元中HIF1α显著高于常氧情况,上述结果差异均具有统计学意义(P＜0.05).结论 建立了一种简单实用的体外分离培养裸鼹鼠海马神经元的方法,初步揭示了裸鼹鼠海马神经元低氧耐受特性,并且该特性与裸鼹鼠海马神经元于低氧情况下高表达HIF1α有关.