酸牦牛乳中乳酸菌降胆固醇作用及胆盐耐受性研究

为了从分离自甘肃酸牦牛乳中的23株乳酸菌中筛选能够同时降低胆固醇并耐受胆盐的乳酸菌,通过邻苯二甲醛法测定降胆固醇能力,并比较各菌株对三种形式的胆盐:牛胆汁、胆酸、甘胆酸钠的耐受性。结果表明,这些菌株在不同条件下的降胆固醇能力差异显著(P<0.05),多数菌株在不含牛胆汁的培养基中培养比添加牛胆汁时有着更好的对胆固醇的去除能力;死菌体对胆固醇的去除能力较弱;对各菌株对不同形式的胆盐耐受能力比较分析得出,各种形式的胆盐对乳酸菌的生长均有抑制作用,抑制顺序由强到弱依次为:甘胆酸钠>胆酸>牛胆汁;各菌株对胆盐的耐受力与降胆固醇能力没有相关性。通过比较选择出H1,I10和W2三株菌,作为功能性菌株为开发应用进行深入研究。     

胆汁酸对大菱鲆幼鱼生长、脂肪代谢酶及血清生化的影响

在基础饲料中分别添加0、0.03%、0.06%、0.09%及0.12%的胆汁酸,配制5组等氮等能的实验饲料(D1、D2、D3、D4、D5),投喂体质量为26.5 g的大菱鲆(Scophthalmus maximus)幼鱼56 d,研究胆汁酸对其生长、体组成、脂肪代谢酶活力及血清生化的影响。结果显示:(1)实验鱼的增重率、特定生长率、蛋白质效率及脂肪效率呈先升后平稳的趋势,均在D3组达到最高值。(2)胆汁酸显著降低了全鱼粗脂肪及粗灰分含量,提高了粗蛋白含量(P0.05);降低了肌肉粗脂肪含量,提高了粗蛋白及粗灰分含量(P0.05)。(3)脂肪酶及脂蛋白脂酶活力呈先升后平稳的趋势;肝脂酶活力显著升高(P0.05)。(4)胆汁酸降低了血清谷丙转氨酶及谷草转氨酶活力,提高了碱性磷酸酶活力(P0.05);总蛋白及白蛋白的含量随胆汁酸含量的增加而升高(P0.05);甘油三酯、总胆固醇及高低密度脂蛋白胆固醇含量随胆汁酸含量的升高而下降(P0.05)。(5)鳗弧菌感染48 h后,D3、D4及D5组的累积死亡率显著低于D1组。以增重率为评价指标,经折线回归分析,体质量26.5 g的大菱鲆幼鱼饲料中胆汁酸的适宜添加量为0.09%。     

Niemann-Pick C1 Like 1 protein is critical for intestinal cholesterol absorption

Dietary cholesterol consumption and intestinal cholesterol absorption contribute to plasma cholesterol levels, a risk factor for coronary heart disease. The molecular mechanism of sterol uptake from the lumen of the small intestine is poorly defined. We show that Niemann-Pick C1 Like 1(NPC1L1) protein plays a critical role in the absorption of intestinal cholesterol. NPC1L1 expression is enriched in the small intestine and is in the brush border membrane of enterocytes. Although otherwise phenotypically normal, NPC1L1-deficient mice exhibit a substantial reduction in absorbed cholesterol, which is unaffected by dietary supplementation of bile acids. Ezetimibe, a drug that inhibits cholesterol absorption, had no effect in NPC1L1 knockout mice, suggesting that NPC1L1 resides in an ezetimibe-sensitive pathway responsible for intestinal cholesterol absorption.     

几种动物胆汁的组分对比及树脂法精制CDCA初探

采用薄层层析法对蟾蜍、兔、鸡、猪及牛胆汁的组分进行了初步分析,结果表明,蟾蜍胆汁中主要是胆酸(CA)和几种不明物质;兔胆汁中主要是去氧胆酸(DCA)和少量的胆酸(CA);鸡胆汁中以鹅去氧胆酸(CDCA)和胆酸(CA)为主;猪胆汁中主要是鹅去氧胆酸(CDCA)、猪去氧胆酸(HDCA)和石胆酸(LCA)为主;牛胆汁中主要是胆酸(CA)、去氧胆酸(DCA)以及少量的鹅去氧胆酸(CDCA).采用紫外扫描皂化胆汁,确定了皂化胆汁的最大吸收波长,并以此为紫外检测波长首次对离子交换树脂法提取CDCA进行了初步研究并得到了高纯度的CDCA精品.     

丹酚酸B调节胆固醇代谢的研究

[目的]研究丹酚酸B对血液胆固醇代谢的调节作用。[方法]选取SD大白鼠,建立高脂模型,进行丹酚酸B干预试验,测定大鼠血液及粪便胆固醇与胆汁酸含量。[结果]丹酚酸B干预的大鼠血液中胆固醇含量显著低于高脂模型组大鼠,粪便中胆固醇及胆汁酸含量显著高于高脂模型组。[结论]丹酚酸B主要通过促进粪便胆固醇与胆汁酸的排泄降低血液中胆固醇。     

降胆固醇乳杆菌的体外评价

对来源于健康青年肠道的15株乳杆菌进行降胆固醇性能体外评价,包括胆盐水解酶(BSH)活性、去除培养基胆固醇能力、胆盐耐受性及酸耐受性4个指标,结果显示:所有菌株都能体外去除胆固醇;2株植物乳杆菌LP25和LP48在12h的去除率达48.41%和47.32%,48h去除率达56.33%和64.85%,其单位质量菌体的胆固醇去除效力也高于其他菌株.LP48同时具有高胆盐水解酶活性及较突出的去胆固醇、耐胆盐、耐酸性能,可作为去除体内胆固醇的潜力菌株进行后续研究.     

Inhibition of cholesterol crystal formation by apolipoproteins in supersaturated model bile

Apolipoproteins A-1 and A-2 were purified from human plasma. At concentrations present in human bile these proteins prolonged the nucleation time of cholesterol monohydrate crystals when added to model systems of supersaturated bile. In contrast, apolipoprotein C-3 and other serum proteins did not have this effect. Also, when human gallbladder bile was fractionated by gel filtration chromatography, apolipoproteins A-1 and A-2 were among the proteins present in a fraction of bile enriched in potent inhibitors of cholesterol crystal nucleation. These findings suggest that apolipoproteins A-1 and A-2 in supersaturated human gallbladder bile could inhibit the rate of formation of solid cholesterol crystals and thus help to prevent spontaneous cholesterol gallstone formation in humans.     

D1 dopamine receptor activation required for postsynaptic expression of D2 agonist effects

D1 and D2 dopamine receptors exert synergistic effects on the firing rates of basal ganglia neurons and on the expression of stereotyped behavior in rats. Moreover, the ability of D2 agonists to induce changes in basal ganglia single unit activity and spontaneous motor activity is dependent upon the presence of endogenous dopamine to stimulate D1 receptors; in rats treated with alpha-methyl-rho-tyrosine to reduce endogenous dopamine levels, the neurophysiological and behavioral effects of the D2 agonist quinpirole are significantly attenuated, while the effects of nonselective agonists like apomorphine, which stimulate both D1 and D2 receptors, or combinations of a D2 agonist and a D1 agonist are not attenuated. Thus, the previously held view that D2 receptors alone are responsible for evoking the changes in behavior and basal ganglia output induced by nonselective dopamine agonists and endogenous dopamine is not supported by these results, which indicate that these phenomena require concurrent stimulation of both dopamine receptor subtypes.     

饲喂益生菌Lactobacillus casei Zhang对高脂日粮大鼠肝脏脂质代谢的作用

【目的】研究不同剂量益生菌L. casei Zhang（2.0×1010 CFU/d、2.0×109 CFU/d和2.0×108 CFU/d）及其发酵乳饮料（2.0×108 CFU/mL/d）对高胆固醇血症大鼠肝脏脂质的治疗作用。【方法】采用高脂饲料诱导高脂血症,采用相应试剂盒测定肝脏总胆固醇水平（TC）和甘油三酯（TG）水平、粪便总胆汁酸水平与胆固醇水平以及血清载脂蛋白ApoAⅠ与ApoB水平。【结果】益生菌各剂量组和发酵饮料组与高脂模型组相比,肝脏总胆固醇水平（TC）和甘油三酯（TG）水平均显著降低(P＜0.05 或P＜0.01)。各试验组均可显著增加高血脂大鼠粪便总胆汁酸水平和血清载脂蛋白ApoAⅠ水平以及显著降低血清载脂蛋白ApoB水平(P＜0.01),但对粪便胆固醇水平影响不明显(P＞0.05)。【结论】益生菌L. casei Zhang主要通过增加总胆汁酸的排出和调节载脂蛋白水平来改善高血脂大鼠肝脏脂质水平。     

类固醇代谢相关基因在大鼠肝再生中表达模式和作用分析

为在基因转录水平了解类固醇代谢相关基因在大鼠肝再生(Liver regeneration,LR)中作用,文章通过搜集网站资料和查阅相关论文等方法获得了参与上述代谢活动的基因,用基因芯片检测了它们在大鼠再生肝中表达情况,初步证实上述基因中83个基因与肝再生相关.肝再生启动(PH后0.5～4 h)、G0/GI过渡(PH后4...     

A G protein couples serotonin and GABAB receptors to the same channels in hippocampus

Both serotonin and the selective gamma-aminobutyric acidB (GABAB) agonist, baclofen, increase potassium (K+) conductance in hippocampal pyramidal cells. Although these agonists act on separate receptors, the potassium currents evoked by the agonists are not additive, indicating that the two receptors share the same potassium channels. Experiments with hydrolysis-resistant guanosine triphosphate (GTP) and guanosine diphosphate analogs and pertussis toxin indicate that the opening of the potassium channels by serotonin and GABAB receptors involves a pertussis toxin-sensitive GTP-binding (G) protein, which may directly couple the two receptors to the potassium channel.     

乳酸菌益生特性及降胆固醇机理的研究

本试验通过对具有良好益生特性乳酸菌的筛选,研究其降胆固醇的机理。我们将分离自内蒙古和新疆地区牧民家庭自制的10份酸马奶中的16株乳酸菌经耐酸、耐胆盐实验,筛选出1株益生特性较好的乳酸菌,为E2301。同时通过胆固醇吸收动力曲线和超声波抗性实验对E2301进行降胆固醇机理研究。结果表明E2301耐受pH3.0人工胃液和0.3%的高胆盐环境的能力分别为57.12%和86.93%。且E2301菌体破碎液中胆固醇含量高达49.96%,说明胆固醇被菌体细胞吸收进入了自身体内。     

猪源降胆固醇肠球菌的分离鉴定

为了筛选益生菌并评价其对血清胆固醇的降解作用,从健康猪胃肠道分离鉴定12株肠球菌,进行体外降胆固醇,对酸和胆盐的耐受性试验,结果表明：分离菌均具有体外降解血清胆固醇的作用,降解率为16．67～48．00％,对pH3．0和0．4％的胆盐具有抵抗力,综合评价E1和E7可以作为降胆固醇的备选益生菌株。     

胆固醇平衡调控中的SREBP途径

胆固醇在生物体内发挥着极其重要的作用。细胞主要通过调节胆固醇的合成、吸收、酯化及外流等途径之间的平衡以维持正常的胆固醇浓度。本文介绍甾醇调控元件结合蛋白(SREBP,Sterolregulatoryelement-bindingproteins)转录因子对胆固醇平衡的调控。SREBP主要调节胆固醇的合成、LDL受体介导的胆固醇的吸收和脂肪酸的合成。SREBP前体是一内质网膜蛋白,SREBP经两次蛋白酶水解后释放出其N端结构域,进入细胞核,激活靶基因的转录。随着对SREBP领域研究的深入,人们对胆固醇平衡调节将认识更多,并有可能开发出更为有效的控制胆固醇的药物。     

Molecular cloning and functional expression of glutamate receptor subunit genes

Three closely related genes, GluR1, GluR2, and GluR3, encode receptor subunits for the excitatory neurotransmitter glutamate. The proteins encoded by the individual genes form homomeric ion channels in Xenopus oocytes that are sensitive to glutamatergic agonists such as kainate and quisqualate but not to N-methyl-D-aspartate, indicating that binding sites for kainate and quisqualate exist on single receptor polypeptides. In addition, kainate-evoked conductances are potentiated in oocytes expressing two or more of the cloned receptor subunits. Electrophysiological responses obtained with certain subunit combinations show agonist profiles and current-voltage relations that are similar to those obtained in vivo. Finally, in situ hybridization histochemistry reveals that these genes are transcribed in shared neuroanatomical loci. Thus, as with gamma-aminobutyric acid, glycine, and nicotinic acetylcholine receptors, native kainate-quisqualate-sensitive glutamate receptors form a family of heteromeric proteins.     

小鼠Lrh-1基因CDS区序列克隆及分析

肝受体类似物-1（liver receptor homolog-1,Lrh-1;NR5A2）是核受体的Ftz-F1亚家族成员,在胚胎发育、分化、胆固醇代谢、胆汁酸的动态平衡以及类固醇激素生成等都具有重要的作用。通过对健康的经产小鼠不同个体间Lrh-1基因CDS（Coding Sequence）特征域区测序及比对分析,结果发现,在LBD（Ligand binding domain）配体结合域区存在较大序列差异,有2种类型,1种与NM₀01159769相似,而另1种则与NG₀12313.1相似,两者序列差异较大,当翻译为多肽链后发现,第2种类型的序列中提前出现终止子,氨基酸数量相对减少83个,但这种缺失未导致该基因功能的丧失,表明该区段与Lrh-1蛋白质功能的不紧密性。     

Nuclear receptor-dependent bile acid signaling is required for normal liver regeneration

Liver mass depends on one or more unidentified humoral signals that drive regeneration when liver functional capacity is diminished. Bile acids are important liver products, and their levels are tightly regulated. Here, we identify a role for nuclear receptor-dependent bile acid signaling in normal liver regeneration. Elevated bile acid levels accelerate regeneration, and decreased levels inhibit liver regrowth, as does the absence of the primary nuclear bile acid receptor FXR. We propose that FXR activation by increased bile acid flux is a signal of decreased functional capacity of the liver. FXR, and possibly other nuclear receptors, may promote homeostasis not only by regulating expression of appropriate metabolic target genes but also by driving homeotrophic liver growth.     

Alteration of lymphocyte trafficking by sphingosine-1-phosphate receptor agonists

Blood lymphocyte numbers, essential for the development of efficient immune responses, are maintained by recirculation through secondary lymphoid organs. We show that lymphocyte trafficking is altered by the lysophospholipid sphingosine-1-phosphate (S1P) and by a phosphoryl metabolite of the immunosuppressive agent FTY720. Both species were high-affinity agonists of at least four of the five S1P receptors. These agonists produce lymphopenia in blood and thoracic duct lymph by sequestration of lymphocytes in lymph nodes, but not spleen. S1P receptor agonists induced emptying of lymphoid sinuses by retention of lymphocytes on the abluminal side of sinus-lining endothelium and inhibition of egress into lymph. Inhibition of lymphocyte recirculation by activation of S1P receptors may result in therapeutically useful immunosuppression.