剃毛和增加胎仔数对KM 小鼠哺乳期能量收支的影响

为探讨最大持续能量收支限制的因素和生理机理,本文测定了增加胎仔数和背部剃毛的KM 小鼠的哺乳
期摄食量和繁殖输出。基础代谢率(BMR)以封闭式流体压力呼吸计测定。结果发现,增加胎仔数对哺乳期体
重、摄食量、热传导率、BMR 和胎仔重的影响不显著;与非剃毛对照组相比,剃毛使哺乳高峰期日平均摄食量
增加了13.8% (P<0.001)、BMR 增加了18.1% (P< 0.01)、热传导增加了30.8% (P< 0.01),但剃毛对体
重、胎仔数和胎仔重的影响不显著;胎仔数与断乳时胎仔重显著正相关,与幼体平均体重显著负相关。BMR 与
母体体重和胎仔重显著正相关。这些结果表明,KM 小鼠哺乳期能量收支受到了限制,剃毛显著增强了KM 小鼠
的散热能力,但未影响繁殖输出;支持“外周限制假说”,不符合“热耗散限制假说”。     

开心散与去茯苓开心散改善拟AD动物学习记忆作用比较

目的比较开心散和去茯苓开心散对AD动物模型学习记忆的改善作用,了解茯苓在开心散复方中的作用。方法连续皮下注射D-半乳糖12周,第9周同时给予中药,第12周开始行为学检测。比较开心散及去茯苓开心散对拟AD动物学习记忆的改善作用;检测脑组织皮层区乙酰胆碱酯酶（AchE）、超氧化物歧化酶（SOD）的活力以及丙二醛（MDA）的含量。结果开心散能显著改善模型动物学习记忆能力;降低模型动物脑组织皮层区乙酰胆碱酯酶活力,升高超氧化物歧化酶活力,降低丙二醛含量;而去除茯苓的开心散对模型动物的学习记忆能力没有改善作用或作用减弱。结论开心散复方具有改善拟AD动物模型学习记忆障碍的作用,而茯苓是开心散复方中起重要作用的成分。     

儿童单纯性肥胖小鼠模型的制作

目的通过调整窝仔数的方法建立幼儿单纯性肥胖模型,并与高脂饲料制备模型进行比较。方法48只雌性KM小鼠产仔鼠后,一半仔鼠数目为14～16只,一半仔鼠调整为6只（雌雄各3只）。仔鼠离乳时或第9周时仔鼠分别饲喂普通饲料或高脂饲料。仔鼠在15周后处死,称重,测量体长、腰围,生殖器重、脂肪重（肾周和生殖器周脂肪）,计算体脂比。结果①BD2组常规饲料饲喂至15周结束后,无论雌雄仔鼠,其体重与BDl组比较差异均有显著性（P〈0．05）,且BD2组体重超过BD1组体重雌性为26．3％,雄性为20．0％。同一处理方式,雌性仔鼠体脂比均高于雄性。②不同时间饲喂高脂饲料,无论调整窝仔数与否,高脂饲料各组仔鼠,无论雌雄,其各组仔鼠体重均比BD1组高（P均〈0．05）;HFD4组雌性和雄性仔鼠体重与BD2组相比差异均存在显著性（P〈0．05）。结论通过调整窝仔数的方法可以成功制备儿童单纯性肥胖模型。在儿童早期肥胖的情况下,成年后过度高脂饮食会导致机体储存更多的脂肪。     

两个封闭群SPF级昆明小鼠遗传背景调查

目的：比较两个封闭群SPF级昆明（ KM）小鼠的遗传差异,调查引进的SPF级KM小鼠封闭繁殖6年后,其遗传构成是否发生变化。方法应用微卫星DNA标记方法对18个位点在两个群体中的遗传差异进行分析,主要包括观察等位基因数（ Na）、有效等位基因数（ Ne）、观察杂合度（ Ho）、期望杂合度（ He）、多态信息含量（PIC ）、Shan-non信息指数、遗传分化系数（ F st）、遗传距离等遗传参数。结果两个封闭群SPF 级KM小鼠在18个微卫星位点共发现67个等位基因,Na为2～8个,平均3．7222个;Ne为1．9459～6．5442,平均2．7966个;Ho为0．4225～1．0000,平均0．8823;He为0．4892～0．8527,平均0．6162;Shannon信息指数0．6792～1．9526,平均1．0598;PIC为0．3680～0．8301,平均0．5317;Fst平均值为0．0159,表明群体间的遗传差异仅1．59％,二者间的遗传距离（DA）为0．0499。结论两个封闭群SPF级KM小鼠遗传结构相似度极高,它们与原引进群体的分化差异极小。     

随机饥饿和重喂食对小鼠能量代谢和行为的影响

为阐明能量代谢和行为的可塑性对动物适应食物资源变化的意义,将成年雄性KM 小鼠随机饥饿驯化4
周,再重喂食驯化4 周。采用食物平衡法测定摄食量、封闭式流体压力呼吸计测定基础代谢率(BMR) 和非颤
抖性产热(NST)、观察法测定行为。随机饥饿使摄食量、消化道重量显著增加,BMR 和NST 显著降低。与对照
组相比,饥饿组休息行为显著增加,活动显著降低。重喂食后,上述指标均恢复到对照组水平,表现出显著的
可塑性。研究结果表明,动物适应难以预测的食物资源短缺的主要策略包括:增加自由取食期间的摄食量;降
低BMR、NST 和活动行为,从而保存身体贮存的能量。能量代谢和活动行为在较短的时间尺度内表现出显著的
可塑性对小鼠适应不可预测的食物资源短缺的应激环境具有重要意义。     

Brain tissue characterisation by infrared imaging in a rat glioma model

Pathological changes associated with the development of brain tumor were investigated by Fourier transform infrared microspectroscopy (FT-IRM) with high spatial resolution. Using multivariate statistical analysis and imaging, all normal brain structures were discriminated from tumor and surrounding tumor tissues. These structural changes were mainly related to qualitative and quantitative changes in lipids (tumors contain little fat) and were correlated to the degree of myelination, an important factor in several neurodegenerative disorders. Lipid concentration and composition may thus be used as spectroscopic markers to discriminate between healthy and tumor tissues. Additionally, we have identified one peculiar structure all around the tumor. This structure could be attributed to infiltrative events, such as peritumoral oedema observed during tumor development. Our results highlight the ability of FT-IRM to identify the molecular origin that gave rise to the specific changes between healthy and diseased states. Comparison between pseudo-FT-IRM maps and histological examinations (Luxol fast blue, Luxol fast blue-cresyl violet staining) showed the complementarities of both techniques for early detection of tissue abnormalities.     

Detection of a gem-diamine and a stable quinonoid intermediate in the reaction catalyzed by serine–glyoxylate aminotransferase from Hyphomicrobium methylovorum

Background

The enzyme l-serine–glyoxylate aminotransferase (SGAT) from Hyphomicrobium methylovorum is a PLP-containing enzyme that catalyzes the conversion of l-serine and glyoxylate to hydroxypyruvate and glycine. The cloned enzyme expressed in Escherichia coli is isolated as a mixture of the E:PLP and E:PMP forms. The PLP form of the enzyme has a maximum absorbance at 413 nm.

Methods

Uv–visible spectra of SGAT were obtained using an HP-8453 diode array spectrophotometer in the absence and presence of substrates and substrate analogs. Pre-steady state kinetic studies were carried out using an OLIS rapid scanning spectrophotometer in the rapid scanning mode.

Results

Incubation of the enzyme with a saturating concentration D-serine leads to a shift in the 413 nm peak to 421 nm that is ascribed to the external aldimine. The reverse stereochemistry of D-serine does not allow for abstraction of the Cα proton by the ε-amine of the active site lysine residue leading to an abortive external aldimine intermediate. Pre-steady state studies pushing SGAT against d-serine leads to a rapid decrease in the 413 nm peak and an increase at ∼ 330 nm with an associated rate constant of 47 s^− 1 at pH 7.6. This is followed by a slower decrease (0.26 s^− 1) at 330 nm and an increase and shift of the 413 nm peak to 421 nm. The intermediate species that absorbs at ∼ 330 nm is attributed to the gem-diamine intermediate. The rate of the fast phase increases with pH and increase in rate is likely due to the deprotonation of an enzymatic group that accepts a proton from the α-amine of d-serine. In the presence of hydroxypyruvate and ammonia the enzyme spectra display an increase in absorbance at 521 nm that occurs on the order of minutes. The shape and position of the 521 nm species is consistent with a quinonoid intermediate.

General significance

The data suggest a non-enzymatic reaction between hydroxypyruvate and ammonia to form an imine which will be in equilibrium with the enamine. A mechanism is proposed by which the enamine reacts with the PLP form of SGAT to generate the stable highly conjugated quinonoid intermediate.     

中国昆明(KM)小鼠线粒体DNA限制性内切酶图谱的研究

线粒体DNA的限制性内切酶图谱在不同的种系及亚种间存在多态性。我们分别用五种限制性内切酶BamHⅠ、EcoRⅡ、HidⅢ、PstⅠ、MspⅠ对60只中国KM小鼠(雌雄各半)的线粒体DNA进行了酶切电泳分析,结果未发现多态性,且这五种限制性内切酶图谱均与BALB/c小鼠相同。这表明中国KM小鼠与绝大多数实验小鼠一样,均起源于欧州的野鼠M.m.domesticu。未见到KM小鼠经其它亚种野鼠母系遗传污染的迹象。     

Evaluation of astatine-211-labeled octreotide as a potential radiotherapeutic agent for NSCLC treatment

Octreotide is a somatostatin (SST) analogue currently used in the treatment of neuroendocrine tumors (NETs) with high binding affinity for the somatostatin receptor-2 (SSTR2) that is also overexpressed in non-small cell lung cancer cell (NSCLC). Alpha-particle-emitting astatine-211 (²¹¹At) is a promising radionuclide with appropriate physical and chemical properties for use in targeted anticancer therapies. To obtain an additional pharmacological agent for the treatment of NSCLC, we present the first investigation of the possible use of ²¹¹At-labeled octreotide as a potential alpha-radionuclide therapeutic agent for NSCLC treatment. ²¹¹At-SPC-octreotide exhibited observable higher uptake in lung, spleen, stomach and intestines than in other tissues. Through histological examination, ²¹¹At-SPC-octreotide demonstrated much more lethal effect than control groups (PBS, octreotide and free ²¹¹At). These promising preclinical results suggested that ²¹¹At labeled octreotide deserved to be further developed as a new anticancer agent for NSCLC.     

昆明小鼠4个可能近交系的基因分型验证

在我国,昆明小鼠作为一种实验动物广泛应用于药理和遗传学相关的研究领域。但由于昆明小鼠属于远交群,而且不同地区的种群间已经出现了严重分化,缺乏具有显著特征的近交系,这使得它在生物学上的应用受到了很大的限制。研究人员已经以昆明小鼠为背景培育出了几个可能的近交系,但由于缺乏可靠的遗传检测,至今未得到广泛的认可和应用。文章收集昆明小鼠的4个已经60代以上兄妹交配繁殖的可能近交系,并以两个标准近交系BALB/c和C57BL/6为参照,利用30个微卫星标记对每个品系的5只小鼠进行了微卫星基因分型,进而分析其遗传纯度。结果发现,品系A1和品系N4在本研究所用的30个位点均呈纯合状态;而T2和N2均在D15Mit16位点呈杂合状态。本研究第一次为我国昆明小鼠近交系的遗传学纯度提供了可靠的分子水平证据。今后应当加强昆明小鼠近交系的标准化,以扩大其在遗传学方面的应用。