多形拟杆菌对糖尿病模型小鼠的影响

目的研究多形拟杆菌(BT)干预糖尿病模型小鼠后对血糖、体重和C肽的影响。方法 (1)用四氧嘧啶(200 mg/kg腹腔注射)制备糖尿病模型小鼠,并分成四组:空白组(n=10)、空白给菌组(n=10)、四氧嘧啶糖尿病模型组(n=11)和模型给菌组(n=11),15 d。(2)BHI血琼脂培养基培养ATCC 29148标准菌株,比浊法测定混悬菌液数量。(3)用多形拟杆菌菌液干预空白给菌组和模型给菌组小鼠,观察15 d中四组小鼠的体重、空腹血糖水平的变化;实时荧光定量PCR测定小鼠肠道内多形拟杆菌的数量;运用酶联免疫法(ELISA)测定血清中C肽的水平。结果 (1)给予菌悬液后,空白给菌组与空白组相比,BT在第3天就可以定植并维持到第15天。与模型组相比,模型给菌组在第15天时可以定植;(2)线性回归相关性分析显示,肠道内多形拟杆菌与体重呈负性相关(r=-0.70,P0.05);与空腹血糖(FPG)呈正性相关(r=0.71,P0.05);与C肽呈负性相关(r=-0.62,P0.05);与胰岛素抵抗指数(HOMA-IR)呈正性相关(r=0.55,P0.05);与胰岛素分泌指数(HOMA-IS)呈负性相关(r=-0.43,P0.05)。结论 (1)外源性灌胃给予多形拟杆菌可以在肠道内定植。(2)肠道内多形拟杆菌的数量变化与糖尿病有相关性。     

多形拟杆菌对肥胖大鼠减肥影响的初步研究及毒性实验

目的研究人体肠道内的多形拟杆菌对肥胖大鼠的减肥作用。方法从人体肠道中提取、分离和鉴定1株多形拟杆菌。建立高能饲料诱发的大鼠肥胖模型,给大鼠灌胃多形拟杆菌菌液,25 d后观察大鼠体重及肠道内多形拟杆菌的数量变化。结果灌胃多形拟杆菌菌液的给药组的大鼠体重与灌胃生理盐水的模型组相比,增长慢（P〈0.05）,差异有显著性,且体内拟杆菌数量多于模型组,差异有显著性（P〈0.05）。结论提示多形拟杆菌菌液对肥胖大鼠有一定的减肥作用。     

维吾尔族新发2型糖尿病患者肠道 乳杆菌属和多形拟杆菌的定量研究

目的定量研究维吾尔族新发2型糖尿病(T2DM)患者和糖耐量正常(NGT)人群肠道中乳杆菌属(Lactobacillus genus)和多形拟杆菌(Bacteroides thetaiotaomicron)的相对水平。方法严格按照纳入标准、排除标准收集维吾尔族新发T2DM患者96例,NGT 98例。提取所有研究对象的粪便细菌总DNA后,采用16SrDNA基因实时荧光定量PCR(Real-time PCR)对乳杆菌属和多形拟杆菌的水平进行定量检测;运用Pearson相关性分析乳杆菌属与研究对象的BMI、腰围、臀围、收缩压(SBP)、舒张压(DBP)、空腹血糖(FBG)、甘油三酯(TG)、总胆固醇(TC)、高密度脂蛋白(HDL-C)和低密度脂蛋白(LDL-C)的相关性。结果 16SrDNA基因Real-time PCR结果显示:(1)与新疆维吾尔族NGT组相比,乳杆菌属水平在新发T2DM中较低,差异有统计学意义(t=8.557,P=0.000)。但是多形拟杆菌在两组差异无统计学意义(t=0.524,P=0.601);(2)新疆维吾尔族上述人群肠道中乳杆菌属水平与FBG呈负相关(r=-0.334,P=0.000),腰围呈负相关(r=-0.170,P=0.018),TC呈负相关(r=-0.178,P=0.013),TG呈负相关(r=-0.157,P=0.030),收缩压呈负相关(r=-0.255,P=0.000)。结论 Lactobacillus genus水平在肠道中降低可能与2型糖尿病的发病,血糖和血脂代谢有关,其机制需进一步研究探讨。     

新疆维吾尔族、哈萨克族2型糖尿患者群肠道菌群中直肠真杆菌与多形拟杆菌的定量研究

目的分析新疆维吾尔族、哈萨克族正常糖耐量人群和2型糖尿患者群肠道菌群中直肠真杆菌与多形拟杆菌的量变差异,探讨肠道菌群与2型糖尿病（T2DM）的相关性。方法采用16S rDNA实时荧光定量RT-PCR技术相对定量法。结果分别比较4组人群肠道菌群中直肠真杆菌与多形拟杆菌数量的对数值,与维吾尔族正常组比较,该民族T2DM组中直肠真杆菌的量差异有统计学意义（P=0.0125）,与哈萨克族正常组比较,该民族T2DM组中直肠真杆菌的量差异有统计学意义（P=0.0261）,两民族正常组、T2DM组之间直肠真杆菌的量差异均未见统计学意义;与维吾尔族正常组比较,该民族T2DM组中多形拟杆菌的量差异有统计学意义（P=0.0003）,哈萨克族T2DM组与正常组中多形拟杆菌的量差异有统计学意义（P=0.0055）,两民族正常组之间多形拟杆菌的量差异有统计学意义（P=0.0154）,两民族T2DM组之间多形拟杆菌的量差异未见统计学意义。结论直肠真杆菌与多形拟杆菌数量的变化,与新疆维吾尔族、哈萨克族2型糖尿病的发生（可能）相关,需要进一步深入探讨。     

多形拟杆菌肝素酶I的SUMO融合表达及酶学特性分析

[目的]克隆多形拟杆菌（Bacteroides thetaiotaomicron）Heparinase I基因,在大肠杆菌（Escherichia coli）中进行基因工程表达获得重组酶SUMO-Bt-HepI和Bt-HepI,并研究其酶学特性。[方法]对B.thetaiotaomicron肝素酶I（Bt-HepI）的基因序列进行密码子优化,PCR扩增得到目的基因,构建表达载体pET-28a-Bt-HepI和pE-SUMO-Bt-HepI,并转化至E. coli Rosetta（DE3）进行表达,分别得到重组产物Bt-HepI和SUMO-Bt-HepI,以肝素钠为底物研究两者的酶学性质。[结果]SDS-PAGE检测显示Bt-HepI和SUMO-Bt-HepI的分子量大小分别约为42.5 kDa和55 kDa。与Bt-HepI相比,融合SUMO-Tag后的肝素酶I比酶活提高了48.9%。酶学性质表明：Bt-HepI和SUMO-Bt-HepI的最适pH和温度均为pH 9、45℃,二者在pH 5-9都具有很好的稳定性,但pH<5时,SUMO-Bt-HepI的耐酸性明显高于Bt-HepI。同时,在温度低于50℃时,SUMO-Bt-HepI的比酶活高于Bt-HepI。此外,Ca²⁺和Mg²⁺对重组肝素酶I具有明显的促进作用,而Cu²⁺、Mn²⁺、Zn²⁺则表现出一定的抑制作用,提示在多形拟杆菌肝素酶I的结构中除了存在已知的Ca²⁺结合位点外,可能还存在Mg²⁺的结合位点。[结论]本研究首次将多形拟杆菌来源的肝素酶I和SUMO-Tag进行了融合表达,使其比酶活得到了显著的提高,为其生产应用奠定了基础。     

多形拟杆菌肝素酶Ⅰ的SUMO融合表达及酶学特性分析

【目的】克隆多形拟杆菌(Bacteroides thetaiotaomicron) Heparinase I基因,在大肠杆菌(Escherichiac。")中进行基因工程表达获得重组酶SUMO-Bt-HepI和Bt-HepI,并研究其酶学特性。【方法】对B.thetaiotaomicron肝素酶I (Bt-HepI)的基因序列进行密码子优化,PCR扩增得到目的基因,构建表达载体pET-28a-Bt-HepI和pE-SUMO-Bt-HepI,并转化至E. colt Rosetta (DE3)进行表达,分别得到重组产物Bt-HepI和SUMO-Bt-HepI,以肝素钠为底物研究两者的酶学性质。【结果】SDS-PAGE检测显示Bt-HepI和SUMO-Bt-HepI的分子量大小分别约为42.5 kDa和55 kDa。与Bt-HepI相比,融合SUMO-Tag后的肝素酶I比酶活提高了 48.9%。酶学性质表明:Bt-HepI和SUMO-Bt-HepI的最适pH和温度均为pH 9、45℃,二者在pH 5-9都具有很好的稳定性,但pH<5时,SUMO-Bt-HepI的耐酸性明显高于Bt-HepI0同时,在温度低于50 ℃时,SUMO-Bt-HepI的比酶活高于Bt-Hepl。此外,Ca^2+和Mg^2+对重组肝素酶I具有明显的促进作用,而CU^2+、Mr^2+、Zt^2+则表现出一定的抑制作用,提示在多形拟杆菌肝素酶I的结构中除了存在已知的Ca2+结合位点外,可能还存在Mg2+的结合位点。【结论】本研究首次将多形拟杆菌来源的肝素酶I和SUMO-Tag进行了融合表达,使其比酶活得到了显著的提高,为其生产应用奠定了基础。     

双歧杆菌对小鼠溃疡性结肠炎模型的影响

目的：研究双歧杆菌对小鼠急性溃疡性结肠炎模型的影响。方法：葡聚糖硫酸钠（DSS）制备小鼠溃疡性结肠炎模型。应用实体显微镜观察整段大肠的粘膜改变情况;普通粪便涂片观察小鼠粪便中细菌的变化,梯度稀释法行粪便菌群分析,了解几种代表性的菌群的改变;一般病理切片,行HE染色,观察镜下病理变化,结果：双歧杆菌 DSS组相比,血便不明显,镜下组织病理改变轻微,肠道菌群无明显紊乱。结论：双歧杆菌对溃疡性结肠炎发生有预防作用,并能减轻症状和病变。     

凝结芽胞杆菌活菌片对实验性腹泻小鼠的治疗作用

目的 观察凝结芽胞杆菌活菌片对氨苄青霉素钠诱发的小鼠腹泻的治疗作用。方法利用氨苄青霉素钠口服诱发小鼠实验性腹泻和肠道菌群失调,然后用凝结芽胞杆菌活菌片,口服,每天2次,共4d,观察治疗后的小鼠排便和肠道菌群变化。结果在各给药组中,治疗第1天有70％～85％的小鼠排正常便,生理盐水组只有10％排正常便（P〈0．01）;治疗第2天给药组中有80％～90％的小鼠排正常便,生理盐水组仅为50％（P〈0．01）。肠道菌群分析结果表明,凝结芽胞杆菌在治疗第2天开始定植,停药第7天后逐渐消失,定植期为10d左右。在各给药组中,治疗第2天肠道菌群开始恢复,第4天均升高到正常,而生理盐水组的恢复比各给药组显著的慢（P〈0．01）。结论 凝结芽胞杆菌活菌片对小鼠实验性腹泻有明显的止泻作用,并能加速肠道菌群的恢复。     

利用雌激素构建小鼠淋病奈瑟菌感染模型

目的探讨用雌激素构建淋病奈瑟菌感染小鼠模型的方法。方法淋病奈瑟菌WHO-A接种经皮下注射苯甲酸雌二醇和真皮下埋植尼尔雌醇片（雌三醇）预处理的雌性ICR小鼠,小鼠阴道拭子接种T-M选择培养基培养分离淋病奈瑟菌,取小鼠阴道分泌物涂片染色观察淋病奈瑟菌感染情况,比较两种雌激素对小鼠淋病奈瑟菌感染的差异。结果与对照组相比,苯甲酸雌二醇小鼠体内淋病奈瑟菌有短时间的定植,而尼尔雌醇组与对照组无差异。结论雌激素（尤其是雌二醇）有利于淋病奈瑟菌在小鼠阴道内的定植。     

马尾松人工林Sloboda多形地位指数模型的研究

将德国生物统计学家Sloboda B的树高生长模型应用于马尾松人工林优势高生长模型模拟中。结果表明,用Sloboda树高生长方程拟合马尾松人工林多形地位指数曲线能获得良好效果,且优于Richards多形地位指数曲线。     

A mathematical model to study the effects of drugs administration on tumor growth dynamics

A mathematical model for describing the cancer growth dynamics in response to anticancer agents administration in xenograft models is discussed. The model consists of a system of ordinary differential equations involving five parameters (three for describing the untreated growth and two for describing the drug action). Tumor growth in untreated animals is modelled by an exponential growth followed by a linear growth. In treated animals, tumor growth rate is decreased by an additional factor proportional to both drug concentration and proliferating cells. The mathematical analysis conducted in this paper highlights several interesting properties of this tumor growth model. It suggests also effective strategies to design in vivo experiments in animals with potential saving of time and resources. For example, the drug concentration threshold for the tumor eradication, the delay between drug administration and tumor regression, and a time index that measures the efficacy of a treatment are derived and discussed. The model has already been employed in several drug discovery projects. Its application on a data set coming from one of these projects is discussed in this paper.     

几种重金属离子对光合细菌生长的抑制效应

光合细菌因其在自然生态系统中的意义与较大的应用价值 ,一直受到国内外科学工作者的重视 ,无论基础研究 ,还是应用研究 ,都取得了重大的进展。其应用研究主要为 3方面 :①用于高负荷有机废水处理 ;②用于水产养殖。它具有作为养殖水质净化剂、用于鱼虾贝幼体培育、作为动物性生物饵料的饵料、作为成鱼成虾的饲料添加剂、防治病等方面作用[6] ;③在农业上的应用。在光照嫌气条件下 ,大多数细菌能有效地固定Ｎ2 ,故在淹水的耕作土壤(如水稻田 )里 ,它能提高土壤Ｎ素水平 ,从而提高土壤肥力 ,光合细菌还能氧化或分解土壤中Ｈ2 Ｓ和胺等有毒化…     

Treatment of potato tubers with a growth promotingPseudomonas sp.: Plant growth responses and bacterium distribution in the rhizosphere

Rifampicin-nalidixic acid resistant mutants of a plant growth promotingPseudomonas sp., strain PsJN, were evaluated for their ability to stimulate in vitro growth of potato. Two mutant strains, MFE (a consistent growth promoter), and IIM15 (an inconsistent growth promoter), were selected for root colonization study. Root colonization of potato plants was consistently greater with MFE than with IIM15. The population density of indigenous bacteria on the root surface of potato plants inoculated with strain MFE was significantly lower as compared to non-bacterized controls and to the plants bacterized with strain IIM15. Soil sterilization did not affect plant growth in any of the treatments. Bacterization of seed tubers with strain MFE stimulated plant emergence and root development in the field, during the first two weeks after planting. Bacterized plants also formed stolons and tubers earlier and had increased yields of commercial size tubers (55 mm) as compared to non-bacterized controls. Root colonization by strain MFE was positively correlated with plant growth stimulation.     

小鼠脑缺血再灌注模型的构建及条件优化

目的:构建小鼠的脑缺血再灌注模型,并对其进行优化。方法:通过对线栓法缺血再灌注脑损伤模型的各个因素的对比实验,在线拴位置、线径、进线深度、小鼠种类等方面对该方法进行了优化改进。结果:造模后的脑片经TTC染色,梗死区域清晰;神经功能评分的体征明显。现有条件下构建的小鼠MCAO模型,成功率可以达到80%以上,成活率可以达到90%以上。与对照组相比,小鼠MCAO模型组血清SOD活性及MDA水平有显著变化(P0.01)。结论:经改进和优化,小鼠脑缺血再灌注模型的成功率和成活率大大提高且症状明显,对缺血缺氧性神经损伤研究具有一定的参考价值。     

The effects of selection for different combinations of weights at two ages on the growth curve of mice

Summary The weights of mice in lines selected for different combinations of high and low body weights at 5 and at 10 weeks of age were recorded from 3 to 21 weeks of age. The average growth curve for each line was computed using the Gompertz function. The growth curves of lines selected for high or low weight at a single age (ST lines) showed large differences in estimates of mature size and small differences in estimates of maturing rate, i.e. of the relative rate of growth to maturity. The growth curves of lines selected by independent culling for divergent combinations of deviations of opposite sign in 5- and 10-week weights (ICL lines) showed little difference in estimates of mature size and a large difference in estimates of maturing rate. The growth curves of lines selected by index for divergence in 5-week weight with no change in 10-week-weight or for divergence in 10-week-weight with no change in 5-week weight showed large differences in estimates of mature size and large differences in estimates of the maturing rate. The relationship between mature size and maturing rate was affected in different ways by the three types of selection.     

Influence of salts and pH on the growth as well as NADH oxidase of the halotolerant bacterium A505

Growth yield of the halotolerant bacterium A505 was increased by the supplement of Na⁺, K⁺, or Rb⁺ into the culture media with pH 7.5, and inhibited by Li⁺ or Cs⁺. In the presence of less than 0.1 M NaCl or KCl alkaline growth media, pH 9.2 to 9.7, afforded optimal growth of this strain. Intracellular ion content of this microbe changed reflecting on the Na⁺ or K⁺ concentration in the media, although it tended to accumulate K⁺ and extrude Na⁺ in the media without NaCl supplemented. A 1.2 to 1.4-fold stimulation of in vitro NADH oxidase activity was obtained by supplement of salts, except for LiCl. The rate of NADH oxidation in the absence of salts correlated with the pH and showed clear maxima at pH about 8, irrespective of growth conditions. In the presence of 0.5 M NaCl or KCl, on the other hand, pH dependence was less significant and showed only a flat maximum at pH around 7. Effects of anions on NADH oxidase were realized following the lyotropic series: SO ₄ ^2- >F^->CH₃COO^->Cl^->I^->SCN^-, aside from NO ₃ ^- , which exhibited the largest stimulation on enzyme activity in all the anions examined.Abbreviations HEPES 4-(2-hydroxyethyl)-1-piperazine-ethanesulfonic acid - HQNO 2-heptyl-4-hydroxyquinoline-N-oxide - MES 4-morpholineethanesulfonic acid - Tris tris(hydroxy-methyl)methylamine     

Tadalafil alleviates preeclampsia and fetal growth restriction in RUPP model of preeclampsia in mice

Background– Tadalafil, a long-acting phosphodiesterase 5 (PDE5) inhibitor, alleviates preeclampsia (PE), and decreases the fetal and infant deaths associated with fetal growth restriction (FGR) in phase II clinical trial. Recently, we demonstrated that tadalafil alleviates FGR and hypertension in the dams with PE induced by l-NAME.Objective–The aim of present study was to clarify the effect of tadalafil in another mouse model of PE, murine reduced uterine perfusion pressure (RUPP) model we have recently developed.Methods–At 14.5 dpc we performed RUPP operation in mice to induce PE, administered the animals with tadalafil or vehicle in the drinking water daily from 15.5 dpc, and sacrificed them at 18.5 dpc for analyses.Results–Tadalafil improved maternal hypertension and glomerular endotheliosis in RUPP mice. Moreover, tadalafil prolonged pregnancy period, and improved survival and growth of the embryos. RUPP increased content of sFlt-1 protein in the placenta, and tadalafil corrected it back to control levels.Conclusion– Tadalafil alleviates PE-like phenotype and FGR in RUPP murine model. RUPP model could help understand the mechanism of how tadalafil works on PE and FGR.     

Primer effects by conspecific odors in house mice: a new perspective in the study of primer effects on reproductive activities

Half a century has passed since the first report of the influence of odors on mice. Odors are known to influence behavior (signaling effect) and affect the physiology (primer effect) of mice. This review focuses on summarizing the primer effects found so far in female and male mice. Odors from conspecifics of the opposite sex had the tendency to enhance reproductive activities, whereas odors from conspecifics of the same sex diminish them. Only 2,5-dimethylpyrazine, one of the odor components identified in group-housed females, has been reported to have a suppressive influence on both males and females by lowering reproductive activities. Studies showed progress from the discovery of phenomena to the identification of odor components that cause such changes in reproductive organs and related neuroendocrinological changes. Compared to studies on the mechanisms of primer effects in females, the mechanisms in males are not yet clarified, and detailed studies on effects on the reproductive organs are still in primitive stages especially for males. Hypotheses on the influence of changes in the concentration of testosterone, estrogen, and prolactin on spermatogenesis and sperm maturation after exposure to odors are discussed.     

CCK-8 induces fever-like regulated hyperthermia and symptoms of sickness behavior in mice: A biotelemetric study

In earlier studies it has been found that rats respond to intracerebroventricular (i.c.v.) injection of cholecystokinin-octapeptide (CCK-8) with a febrile response characterized by rises of heat production and core temperature together with tail-skin vasoconstriction mediated by CCK2 receptors. Biotelemetric investigations of the same species have additionally shown that CCK-induced fever is accompanied by decreased locomotor activity. Similar data for mice have not been reported so far. In the present studies C57BL/6 mice were infused i.c.v. for 3 days with CCK-8 to see effects on body core temperature, locomotor activity, food intake and body weight. Biotelemetric monitoring disclosed a rise in daylight core temperature and a fall of night-time locomotor activity both lasting beyond the time of i.c.v. infusions. Food intake was suppressed only during infusion, while a significant decrease of body weight was sustained after the end of CCK-8 infusion. It is concluded that similar to rats mice also respond to i.c.v. infusion of CCK-8 with a fever-like (regulated) hyperthermia and some components of sickness behavior as measured by biotelemetry, and thus a CCK-mediated mechanism may contribute to fever genesis also in mice.