亚磁场引起小鼠昼夜节律改变和热痛觉敏感增加（英文）

地外空间的亚磁场环境是影响宇航员健康的一种潜在风险因素.动物和人体实验表明,亚磁场显著影响个体行为和神经系统功能.但是,目前尚缺乏亚磁场对动物行为和生理等多方面影响的系统检测数据.本文构建了一个适用于动物饲养的亚磁场环境(500 n T),并系统检测了30天亚磁场处理对成年雄鼠(C57BL/6,4~6周龄,(20±2)g)的昼夜周期、痛觉、情绪及激素水平的影响.实验结果表明,对比地磁场中饲喂对照组,亚磁场中小鼠的昼夜饮水节律改变、热敏痛觉耐受能力和整体活动水平降低,但是没有发生焦虑或抑郁情绪.亚磁场处理后,小鼠血清去甲肾上腺素水平显著下降.这些结果说明一个月连续亚磁场处理扰乱动物的昼夜活动节律和内分泌,随后可能导致其感知觉能力的变化和运动机能的下降.     

亚磁场引起小鼠昼夜节律改变和热痛觉敏感增加

地外空间的亚磁场环境是影响宇航员健康的一种潜在风险因素．动物和人体实验表明,亚磁场显著影响个体行为和神经系统功能．但是,目前尚缺乏亚磁场对动物行为和生理等多方面影响的系统检测数据．本文构建了一个适用于动物饲养的亚磁场环境(< 500 nT),并系统检测了30天亚磁场处理对成年雄鼠(C57BL/6,4～6周龄,(20 ± 2) g)的昼夜周期、痛觉、情绪及激素水平的影响．实验结果表明,对比地磁场中饲喂对照组,亚磁场中小鼠的昼夜饮水节律改变、热敏痛觉耐受能力和整体活动水平降低,但是没有发生焦虑或抑郁情绪．亚磁场处理后,小鼠血清去甲肾上腺素水平显著下降． 这些结果说明一个月连续亚磁场处理扰乱动物的昼夜活动节律和内分泌,随后可能导致其感知觉能力的变化和运动机能的下降．     

长期亚磁场处理降低成年雄性小鼠肌肉组织的线粒体功能和运动能力（英文）

亚磁场是深空载人航天任务中的一个关键风险因素.研究表明,亚磁场影响动物多种运动相关行为,但长期亚磁场处理对成年个体运动能力的影响还需要进一步的研究,以评估深空飞行任务中亚磁场的潜在风险.本研究利用三轴亥姆霍兹线圈系统模拟的亚磁环境,长期(一个月)曝露处理成年雄性C57BL/6小鼠,并从行为、组织、细胞、分子水平研究其对小鼠运动能力的影响.相比于地磁组对照,亚磁组小鼠的耐力显著下降.并且,其骨骼肌中柠檬酸水平和肌膜下线粒体数量的下降,以及骨骼肌线粒体形态的变化,表明亚磁场诱导了肌肉线粒体功能抑制,并可能导致其与耐力密切相关的能量代谢的下降.我们的研究结果为线粒体直接响应亚磁场提供了体内证据,并且提示线粒体相关指标可能用于亚磁场效应的风险评估和干预药物的开发.     

长期亚磁场处理降低成年雄性小鼠肌肉组织的线粒体功能和运动能力*

亚磁场是深空载人航天任务中的一个关键风险因素。研究表明,亚磁场影响动物多种运动相关行为,但长期亚磁场处理对成年个体运动能力的影响还需要进一步的研究,以评估深空飞行任务中亚磁场的潜在风险。本研究利用三轴亥姆霍兹线圈系统模拟的亚磁环境,长期（一个月）曝露处理成年雄性C57BL/6小鼠,并从行为,组织,细胞,分子水平研究其对小鼠运动能力的影响。相比于地磁组对照,亚磁组小鼠的耐力显著下降。并且,其骨骼肌中柠檬酸水平和肌膜下线粒体数量的下降,以及骨骼肌线粒体形态的变化,表明亚磁场诱导了肌肉线粒体功能抑制,并可能导致其与耐力密切相关的能量代谢的下降。我们的研究结果为线粒体直接响应亚磁场提供了体内证据,并且提示线粒体相关指标可能用于亚磁场效应的风险评估和干预药物的开发。     

夹竹桃麻素对双酚a诱导的成年雄性小鼠精子损伤作用的实验研究

目的:研究NADPH氧化酶抑制剂夹竹桃麻素(Apocynin)对双酚a(Bisphenol a,BPA)诱导的成年雄性小鼠精子损伤过程中的作用。方法:成年雄性小鼠给以BPA刺激,给以Apocynin(1 mg/kg/day和10 mg/kg/day,分别处理7 day)进行治疗,观察其对BPA诱导的成年雄性小鼠精子损伤的作用。结果:BPA处理组小鼠附睾精子数目和活力明显降低,血清中睾酮和黄体生成素水平明显减少;Apocynin治疗明显增加BPA处理组小鼠附睾中精子数目和活力,但是对血清中睾酮和黄体生成素水平没有明显影响。另外,BPA处理组小鼠睾丸中丙二醛(Malonaldehyde,MDA)水平明显增加;Apocynin治疗明显抑制了BPA处理组小鼠睾丸中MDA水平。结论:NADPH氧化酶抑制剂Apocynin减轻BPA诱导的成年雄性小鼠精子损伤。     

侵袭性肺曲霉菌患者血清半乳甘露聚糖动态变化及与CT影像学关系

目的观察侵袭性肺曲霉菌感染患者抗真菌治疗前后肺泡灌洗液及血清中半乳甘露聚糖(GM)的水平变化、CT影像学特征及血清中性粒细胞数与GM试验阳性率之间的关系,患者血清中性粒细胞值与GM试验阳性率之间的关系。方法连续性纳入60例确诊侵袭性肺曲霉菌感染患者,观察抗真菌治疗前后肺泡灌洗液和血清GM试验动态水平变化。单因素Logistic回归分析CT侵犯肺叶数、空气新月征、晕轮征、血清中性粒细胞值与GM的关系。结果抗真菌治疗前患者肺泡灌洗液GM平均值均高于血清GM平均值(0.62±0.08mg/L,60.0%;0.51±0.07mg/L,31.6%)。同抗真菌治疗前比,患者抗真菌治疗后1个月、2个月、3个月、6个月肺泡灌洗液GM值快速降低(P0.05),而血清GM数值缓慢降低,仅在第3个月、第6个月降低(P0.05)。患者CT侵犯肺叶数、晕轮征与肺泡灌洗液、血清中性粒细胞值GM试验阳性率显著相关。结论肺泡灌洗液及血清GM试验可作为IFD疾病诊断及治疗的重要辅助指标。CT影像学特征、血清中性粒细胞值与GM试验阳性率显著相关。     

裂殖壶藻藻油DHA对高脂饮食诱导肥胖小鼠的影响

【目的】肥胖症是一种慢性代谢类疾病,具有较高的发病率和高危后果。研究表明,n-3多不饱和脂肪酸(n-3 Polyunsaturated fatty acids,n-3 PUFAs),特别是二十二碳六烯酸(Docosahexaenoic acid,DHA)对与肥胖症相关疾病有较好的防治效果,对体内脂质代谢有重要的调节作用。探讨裂殖壶藻(Schizochytrium sp.)藻油DHA对高脂饮食诱导肥胖小鼠体重、脂肪组织重量、血脂、肝和脂肪组织病理形态和脂质代谢相关基因表达的影响。【方法】通过高脂饮食建立小鼠肥胖模型,以体重增幅15%为标准分出肥胖小鼠。试验共分五组:(1)低脂对照组;(2)高脂模型组;(3)高脂+低剂量藻油组(50 mg DHA/kg);(4)高脂+中剂量藻油组(100 mg DHA/kg);(5)高脂+高剂量藻油组(200 mg DHA/kg)。其中,藻油处理组灌服相应剂量藻油,低脂对照组和高脂模型组灌胃同等体积玉米油。处理9周后,腹腔麻醉,摘眼球取血并分离血清,测血清中甘油三酯、胆固醇和高密度脂蛋白含量;之后处死小鼠,分离附睾、肾周和肠系膜脂肪组织及肝脏,称湿重;附睾脂肪和肝组织切片进行HE染色,观察病理变化情况;利用RT-PCR检测附睾脂肪组织中激素敏感脂酶(Hormone sensitive lipase,HSL)基因的m RNA表达情况。【结果】藻油处理组小鼠体重没有显著下降,但是腹部脂肪重量显著降低、脂肪细胞体积明显小于高脂模型组;同时血清中甘油三酯、胆固醇含量显著降低,肝组织异位脂肪堆积明显减少;脂肪组织中HSL基因的表达水平显著提高。【结论】裂殖壶藻藻油DHA处理能显著降低高脂饮食导致的小鼠腹部脂肪积累并改善血脂,可能有利于肥胖症的防治。     

运动预处理部分抵抗小鼠长期高脂饮食喂养引起的脂代谢紊乱

已有研究表明运动具有广泛的健康效应,其能够通过改善机体代谢等机制防治慢性疾病。新近研究表明运动预处理(即在疾病发生、发展之前给予运动干预)具有一定的心脏保护效应,但其能否抵抗高脂饮食诱导的肥胖和代谢紊乱尚不清楚。本研究旨在明确运动预处理对长期高脂饮食喂养小鼠的体重和代谢的影响,并探讨其可能机制。C57BL/6小鼠(4周龄)在经过3个月的游泳训练或安静对照后,给予正常饮食(normal diet, ND)或高脂饮食(high fat diet, HFD)喂养4个月。结果显示：3个月的游泳训练能够显著降低小鼠血糖、提高葡萄糖耐量和增加抓力。运动预处理不能改善由于HFD喂养引起的体重增加,但能够改善由于HFD喂养引起的糖耐量异常。运动预处理对ND和HFD喂养小鼠的运动能力和运动节律均无明显影响。HFD喂养后小鼠血清总胆固醇、低密度脂蛋白水平增加,皮下脂肪和附睾脂肪含量增加。运动预处理能够显著降低ND喂养小鼠循环游离脂肪酸和低密度脂蛋白水平。运动预处理能够增加HFD喂养小鼠的循环高密度脂蛋白水平,降低循环低密度脂蛋白水平,但不影响皮下脂肪和附睾脂肪的重量。HFD喂养增加肝脏重量,提高肝脏总胆固...     

大蒜油诱发小鼠中性粒细胞的抗肿瘤活性

大蒜油诱发的小鼠腹腔中性粒细胞具有活跃的形态学特征,显示出强阳性的过氧化氢酶反应。与酵母聚糖(zymosan A)共同孵育,CeCl_3电镜细胞化学沉淀技术显示,中性粒细胞吞噬zymosan A后呈现强烈的H_2O_2生成反应。大蒜油诱发的大鼠腹腔中性粒细胞与~(51)Cr标记的S180肿瘤细胞共同孵育,它与肿瘤细胞的结合能力以及对肿瘤细胞的杀伤能力都高于糖原诱发的小鼠腹腔中性粒细胞。     

亚磁场对雄性小鼠神经递质、 激素和血常规的影响

本研究主要是探讨连续亚磁场环境暴露对C57BL/6雄性小鼠（Mus musculus domesticus）神经递质、激素含量和血常规参数的影响。实验组为亚磁场暴露组（1.1 ± 0.5）μT,对照组为地磁场组（53.3 ± 0.2）μT。实验对象分别为3周龄幼年小鼠和8周龄成年小鼠。幼年小鼠随机分为实验组与对照组,每组42 只;成年小鼠也随机分为实验组与对照组,每组36只。幼年小鼠在两种磁场环境中的暴露时间为1 ~ 5周,成年小鼠的暴露时间为1、3、6、9、12周。采用液相色谱-质谱联用法（LC-MS）检测小鼠脑组织及血清中的神经递质含量,包括5-羟色胺（5-HT）、多巴胺（DA）、乙酰胆碱（Ach）、去甲肾上腺素（NA）、γ-氨基丁酸（GABA）;用 ELISA 方法检测小鼠血清中的激素含量,包括甲状腺素（T4）、生长激素（GH）、去甲肾上腺素（NA）;血常规在北京大学医学部检测。采用独立样本 t 检验对实验组与对照组的检测结果进行差异分析。与地磁场组相比,亚磁场组幼年小鼠脑组织多巴胺（DA）含量在第5周有显著降低（P < 0.05）,血清中的甲状腺素（T4）含量在第 2和5 周有显著降低（P < 0.05）,去甲肾上腺素（NA）含量在第4周出现显著性降低（P < 0.01）;与地磁场组相比,成年小鼠脑组织5-羟色胺（5-HT）、去甲肾上腺素（NA）含量在处理1周时均出现显著性降低（P < 0.05）,血清中5-羟色胺（5-HT）含量在第3周也出现显著性降低（P < 0.01）,甲状腺素（T4）含量在第 3、6、12 周出现显著性降低（P < 0.05）。血常规结果显示,成年和幼年小鼠的白细胞（WBC）在暴露早期第1周和第2周分别出现显著性增多（P < 0.01）,其他参数基本无变化。本研究发现,两个年龄段的小鼠对亚磁场响应的指标不完全一致,仅甲状腺素（T4）在两个年龄段小鼠的体内都出现显著性降低。通过本研究说明,甲状腺素（T4）、5-羟色胺（5-HT）、去甲肾上腺素（NA）、多巴胺（DA）和白细胞（WBC）可能是不同年龄段小鼠对亚磁场环境暴露较为敏感的生理指标,可在今后的亚磁场生物效应研究中重点关注。     

Elimination of the geomagnetic field stimulates the proliferation of mouse neural progenitor and stem cells

Living organisms are exposed to the geomagnetic field (GMF) throughout their lifespan. Elimination of the GMF, resulting in a hypogeomagnetic field (HMF), leads to central nervous system dysfunction and abnormal development in animals. However, the cellular mechanisms underlying these effects have not been identified so far. Here, we show that exposure to an HMF (<200 nT), produced by a magnetic field shielding chamber, promotes the proliferation of neural progenitor/stem cells (NPCs/NSCs) from C57BL/6 mice. Following seven-day HMF-exposure, the primary neurospheres (NSs) were significantly larger in size, and twice more NPCs/NSCs were harvested from neonatal NSs, when compared to the GMF controls. The self-renewal capacity and multipotency of the NSs were maintained, as HMF-exposed NSs were positive for NSC markers (Nestin and Sox2), and could differentiate into neurons and astrocyte/glial cells and be passaged continuously. In addition, adult mice exposed to the HMF for one month were observed to have a greater number of proliferative cells in the subventricular zone. These findings indicate that continuous HMF-exposure increases the proliferation of NPCs/NSCs,in vitro and in vivo. HMF-disturbed NPCs/ NSCs production probably Affects brain development and function, which provides a novel clue for elucidating the cellular mechanisms of the bio-HMF response.     

Magnetic Shielding Accelerates the Proliferation of Human Neuroblastoma Cell by Promoting G1-Phase Progression

Organisms have been exposed to the geomagnetic field (GMF) throughout evolutionary history. Exposure to the hypomagnetic field (HMF) by deep magnetic shielding has recently been suggested to have a negative effect on the structure and function of the central nervous system, particularly during early development. Although changes in cell growth and differentiation have been observed in the HMF, the effects of the HMF on cell cycle progression still remain unclear. Here we show that continuous HMF exposure significantly increases the proliferation of human neuroblastoma (SH-SY5Y) cells. The acceleration of proliferation results from a forward shift of the cell cycle in G1-phase. The G2/M-phase progression is not affected in the HMF. Our data is the first to demonstrate that the HMF can stimulate the proliferation of SH-SY5Y cells by promoting cell cycle progression in the G1-phase. This provides a novel way to study the mechanism of cells in response to changes of environmental magnetic field including the GMF.     

Effect of liposomal muramyl tripeptide phosphatidylethanolamine and indomethacin on hematopoietic recovery in irradiated mice

The effects of liposomal muramyl tripeptide phosphatidylethanolamine (MTP-PE/MLV, radioprotective immunomodulator; 10 mg/kg) and indomethacin (INDO, inhibitor of prostaglandin production; 2 mg/kg) on post-irradiation recovery of hematopoietic functions in mice were investigated. Two agents with distinct radioprotective mechanisms were administered alone or in combination 24 h and 3 h before exposure to 7 Gy (60)Co radiation. In the post-irradiation period (3-14 days) combined pre-treatment of mice accelerated recovery of bone marrow cellularity, weight of spleen and myelopoietic and erythropoietic activity in both hematopoietic organs, compared to treatment with MTP-PE/MLV or indomethacin alone. In the peripheral blood, improved radioprotective effects of combined drug administration were found in the recovery of reticulocytes and platelet count. No further significant differences in the recovery of leukocyte count were observed in the examined groups until post-irradiation day 14. Within the first 3-6 post-irradiation days, the bone marrow and peripheral blood smears of mice pre-treated with indomethacin alone or its combination with MTP-PE/MLV more frequently featured blast cells and large cells with abundant cytoplasm which could be considered the hematopoietic stem cells.     

Suppression of nonspecific resistance of the body under the effect of extremely high frequency electromagnetic radiation of low intensity

The dynamics of leukocyte number and functional activity of peripheral blood neutrophils under whole-body exposure of healthy mice to low-intensity extremely-high-frequency electromagnetic radiation (EHF EMR, 42.0 GHz, 0.15 mW/cm2, 20 min daily) was studied. It was shown that the phagocytic activity of peripheral blood neutrophils was suppressed by about 50% (p < 0.01 as compared with the sham-exposed control) in 2-3 h after the single exposure to EHF EMR. The effect persisted for 1 day after the exposure, and then the phagocytic activity of neutrophils returned to the norm within 3 days. A significant modification of the leukocyte blood profile in mice exposed to EHF EMR for 5 days was observed after the cessation of exposures: the number of leukocytes increased by 44% (p < 0.05 as compared with sham-exposed animals), mostly due to an increase in the lymphocyte content. The supposition was made that EHF EMR effects can be mediated via the metabolic systems of arachidonic acid and the stimulation of adenylate cyclase activity, with subsequent increase in the intracellular cAMP level. The results indicated that the whole-body exposure of healthy mice to low-intensity EHF EMR has a profound effect on the indices of nonspecific immunity.     

恒定磁场对小鼠空间记忆形成的影响

目的探讨不同照射时间的恒定磁场作用对小鼠空间记忆形成的影响。方法应用水迷宫学习模型测定并对比4小时恒定磁场照射组、3小时恒定磁场照射组、2小时恒定磁场照射组和无磁场照射的正常对照组动物的空间记忆能力。结果水迷宫学习训练的实验表明第一个训练日中,4小时磁场处理组动物与正常对照组比较,动物到达水下平台所需时间延长,且具有显著性差异(P<0.05);3小时磁场处理组与正常对照组比较,动物到达水下平台所需时间缩短,且具有显著性差异(P<0.05);第二个训练日中,2小时或3小时磁场处理组与正常对照组比较,动物到达水下平台所需时间延长,且均具有显著性差异(P<0.05)。第三、四、五连续3个训练日中,3组磁场处理组动物到达水下平台所需的时间与正常对照组相比较均不具有显著性差异(P>0.05)。结论一定时间的磁场处理对小鼠空间记忆的形成有促进或损伤作用,究竟是促进还是损伤有可能取决于一个作用“窗口”问题。     

磁场作用对小鼠抗应激能力的影响

目的 :探讨磁场作用对小鼠抗应激能力的影响。方法 :对磁场处理 30分钟和 1 5分钟的两组实验组与非磁场处理的正常对照组进行游泳耐疲劳运动时间的比较。结果 :游泳耐疲劳运动实验表明 30分钟磁场处理组与正常对照组比较 ,动物游泳耐疲劳运动时间延长 ,且具有显著性差异 (p <0 .0 5 ) ;1 5分钟磁场处理组与正常对照组比较 ,动物游泳耐疲劳运动时间无明显差异 (p >0 .0 5 ) ;30分钟磁场处理组与 1 5分钟磁场处理组比较 ,动物游泳耐疲劳运动时间延长 ,且具有显著性差异 (p <0 .0 5 )。结论 :在一段时间( 30天 )内 ,每天给予小鼠 30分钟的磁场处理明显提高了小鼠的抗应激能力 ,而磁场处理 1 5分钟对小鼠的抗应激能力不产生影响。     

Microenvironmental Scenario of the Bone Marrow of Inorganic Arsenic-Exposed Experimental Mice

Exposure to arsenic on a regular basis, mainly through drinking water, agricultural pesticide, and sometimes therapeutic dose, results in various diseases of different tissues including the bone marrow hematopoietic system. Hematopoiesis is a dynamic process by which bone marrow (BM) hematopoietic stem/progenitor cells (HSPCs) generate a relatively constant pool of functionally mature blood cells by the support of microenvironmental components. The present study has been aimed to understand stem cell microenvironmental status during arsenic toxicity and the consequent reflection of dysregulation involving the hematopoietic machinery in experimental mice. Swiss albino mice were experimentally exposed to 10 μg arsenic trioxide/g body weight through oral gavage and 5 μg arsenic trioxide/g body weight intraperitoneally for a period of 30 days. Altered hemogram values in peripheral blood reflected the impaired hematopoiesis which was further validated by the reduced BM cellularity along with the deviated BM cell morphology as observed by scanning electron microscopy post arsenic exposure. The stromal cells were unable to establish a healthy matrix and the sustainability of hematopoietic progenitors was drastically affected in arsenic-exposed mouse groups, as observed in in vitro explant culture. The inability of stromal cells to establish supportive matrix was also explained by the decreased adherent colony formation in treated animals. Furthermore, the flow cytometric characterization of CXCR4⁺ and Sca-1⁺ CD44⁺ receptor expressions confirmed the dysregulation in the hematopoietic microenvironment. Thus, considering the importance of microenvironment in the maintenance of HSPC, it can be concluded that arsenic toxicity causes microenvironmental damage, leading to niche derangement and impaired hematopoiesis.     

磁场作用对小鼠学习记忆的影响

目的 :探讨磁场作用对小鼠学习记忆能力的影响。方法 :应用水迷宫学习模型测定并对比 30分钟磁场处理组、1 5分钟磁场处理组和非磁场处理的正常对照组动物的空间学习记忆能力。结果 :水迷宫学习训练的实验表明 30分钟磁场处理组与正常对照组比较 ,动物到达水下平台的时间延长 ;游程增加 ;平均游速减慢 ,且均具有显著性差异 (p <0 .0 5)。 1 5分钟磁场处理组与正常对照组比较 ,动物到达水下平台的时间延长 ,且具有显著性差异 (p <0 .0 5) ;游程和平均速度与正常对照组相比无显著性差异 (p >0 .0 5)。结论 :磁场处理 30分钟或 1 5分钟损伤小鼠的空间学习记忆能力 ,且以 30分钟的磁场处理作用较强