烟酰水杨酸对鹌鹑实验性动脉粥样硬化的预防作用

目的探讨烟酰水杨酸(N icotinylsalicylic ac id,NSA)对高脂饲料诱导的鹌鹑实验性动脉粥样硬化的预防作用。方法91只♂朝鲜种鹌鹑,随机分为6组,组1:普通饲料组(对照组)、组2:高脂饲料组(造模组)、组3:高脂饲料+NSA150 mg.kg-1.d-1、组4:高脂饲料+NSA 300 mg.kg-1.d-1、组5:高脂饲料+烟酸75 mg.kg-1.d-1+乙酰水杨酸75 mg.kg-1.d-1、组6:高脂饲料+烟酸150 mg.kg-1.d-1。动态监测(0、4和8 wk)其血浆总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)和丙二醛(MDA),8 wk末处死动物,观察主动脉及左、右头臂动脉病理变化和TC、TG含量;观察心脏病理变化。结果高脂饲料可使鹌鹑血脂发生紊乱,血浆TC、TG水平增加,LDL-C、MDA明显升高,HDL-C水平下降;主动脉及左、右头臂动脉壁TC、TG含量升高,并有明显的动脉粥样硬化斑块形成。NSA可降低高脂饲料喂养的鹌鹑血浆TC、TG、LDL-C、MDA水平,升高HDL-C水平,动脉壁TC、TG含量降低,主动脉及左、右头臂动脉的AS斑块形成减轻。结论NSA对高脂饲料诱导的鹌鹑实验性动脉粥样硬化有预防作用。     

花椒籽油对大鼠动脉粥样硬化的作用研究

目的探究花椒籽油对大鼠脂质代谢的影响,从而探讨其对动脉粥样硬化的作用。方法 24只健康SD大鼠随机分为3组:对照组、高脂组、花椒籽油组,对照组普通饲料喂养,其余两组均高脂饲料喂养,花椒籽油组同时给予花椒籽油灌胃,8周后腹主动脉采血,测定其TC、TG、HDL-C的含量。结果与高脂组相比,花椒籽油组血清TC、TG显著降低(P<0.01,P<0.05),HDL-C显著升高(P<0.01)。结论花椒籽油可有效降低高脂大鼠的TC、TG含量,升高HDL-C含量,对大鼠的动脉粥样硬化形成有一定的防治作用。     

烟酸对幼年肥胖大鼠血脂及血管内皮粘附功能的影响

目的研究烟酸对幼年肥胖大鼠血脂及血管内皮粘附功能的影响,探讨烟酸防治动脉粥样硬化(AS)的作用机制。方法Wistar大鼠随机分为对照组和试验组,分别饲予基础饲料和高脂饲料,8周后肥胖大鼠造模成功。肥胖大鼠再随机分为3组:A组:单纯控制食谱,B组:控制食谱+烟酸,F组:继续高脂饮食。原对照组继续饲予基础饲料,为N组。干预12周后,处死全部大鼠,测定血脂指标:总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白(HDL)、低密度脂蛋白(LDL)、计算动脉粥样硬化指数(AI);血管内皮粘附因子:血清可溶性细胞间粘附分子1(sICAM-1),免疫组化法检测腹主动脉ICAM-1蛋白的表达,RT-PCR法检测腹主动脉ICAM-1mRNA的表达。结果与F组比较,B组的TC、TG、LDL、AI、sICAM-1、ICAM-1蛋白和mRNA表达水平显著降低,HDL显著升高,且均与N组无显著差异。结论控制食谱联合烟酸可以改善血脂、血管内皮粘附功能,因此调节血脂紊乱和血管内皮粘附功能障碍是烟酸类药物改善AS预后的可能机制。     

西红花酸对动脉粥样硬化大鼠血脂及LOX-1表达的影响

目的研究西红花酸对动脉粥样硬化大鼠血脂及LOX-1表达的影响。方法健康SD雄性大鼠,随机分为4组:空白对照组、模型组、西红花酸高剂量组、西红花酸低剂量组。高脂饲料建立大鼠实验性动脉粥样硬化模型,测定大鼠血清总胆固醇、甘油三酯、低密度脂蛋白、高密度脂蛋白。同时取主动脉做病理切片检查。RT-PCR、Westernblotting技术检测主动脉LOX-1的基因与蛋白表达水平,观察西红花酸对其血管平滑肌细胞LOX-1表达的影响。结果高、低剂量的西红花酸能显著降低动脉粥样硬化大鼠血清TC、TG和LDL-C含量;明显降低主动脉LOX-1的表达。结论西红花酸可明显下调动脉粥样硬化大鼠LOX-1的表达。     

瑞舒伐他汀与普罗布考抗大鼠动脉粥样硬化机制研究

目的 探讨选择性HMG-COA还原酶抑制剂瑞舒伐他汀(Rosuvastatin)与抗氧化剂普罗布考(Probucol)对大鼠动脉粥样硬化形成的影响,并研究其机制。方法 60只Wistar雄性大鼠,随机分5组,正常饮食组(A组),高脂饮食组(B组),瑞舒伐他汀组(C组),普罗布考组(D组),瑞舒伐他汀联合普罗布考组(E组),每组12只。以高脂饲料喂养加腹腔注射VD₃建立大鼠动脉粥样硬化(AS)模型。第9周,C、D、E组大鼠在高脂喂养基础上给予药物干预。16周末处死各组大鼠,采血检测血脂,酶联免疫吸附法检测血浆氧化低密度脂蛋白(OX-LDL),血清丙二醛(MDA)、超氧化物歧化酶(SOD)、血管内皮细胞钙黏蛋白(VE-cadherin);免疫组织化学法检测主动脉血小板内皮细胞黏附分子1(PECAM-1)的表达;光镜下观察主动脉血管壁病理组织学改变。结果 与A组比较,B、C、D、E组大鼠血清总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白(LDL-C)显著增高(P<0.01),高密度脂蛋白(HDL)降低(P<0.01),OX-LDL、VE-cadherin、MDA升高(P<0.01),而SOD降低(P<0.01),光镜下观察主动脉内膜厚度增加,内膜损害严重,动脉血管PECAM-1表达升高(P<0.01)。与B组比较,C、D、E组大鼠血清TC、LDL-C含量降低(P<0.01),OX-LDL、VE-cadherin、MDA明显下降(P<0.01),SOD升高(P<0.05),光镜下血管内膜较B组薄,内膜损害减轻,PECAM-1表达降低(P<0.01)。与C组比较,D组和E组OX-LDL、MDA降低(P<0.05),SOD升高(P<0.05)。结论 普罗布考降低TC、LDL-C作用,以及抗炎效用与瑞舒伐他汀疗效相似,普罗布考有显著的抗氧化作用,抗氧化疗效优于瑞舒伐他汀,两药合用可减缓AS进展。     

氢化可的松与辛伐他汀对高脂饮食大鼠动脉NF κB与ICAM 1含量的影响

目的观察氢化可的松与辛伐他汀对高脂血症模型大鼠动脉核转录因子 κB (NF κB) 、血管细胞间粘附因子 1(ICAM 1)含量的影响，探讨其防治动脉粥样硬化(AS)的机制。方法将普通级SD大鼠随机分为空白组，高脂组，氢化可的松高、低剂量组和辛伐他汀组。空白组饲喂基础饲料，其他组饲喂造模饲料并给予相应药物， 16周后采用放射免疫法检测血清中三酰甘油（TG）、总胆固醇（TC）、低密度脂蛋白胆固醇(LDL C)含量；制作主动脉常规及免疫组化切片，观察内膜、肌层厚度及NF κB 、ICAM 1阳性细胞比例。结果氢化可的松高、低剂量组，辛伐他汀组主动脉内膜及肌层厚度明显薄于高脂组，厚于空白组，其NF κB 、ICAM 1阳性细胞率显著低于高脂组，高于空白组。结论氢化可的松、辛伐他汀有抗AS作用,其机制可能通过抑制NF κB激活和降低ICAM 1分泌有关。     

吡格列酮对高脂饮食大鼠胸主动脉PPARγ-核因子-κB途径的影响

目的观察吡格列酮对高脂饮食大鼠胸主动壁脉过氧化物酶增殖体激活受体(PPAR)γ mRNA表达及核因子(NF)-κB活性影响。方法雄性SD大鼠24只,随机分为3组:基础组(C)、高脂组(HL)、吡格列酮组(PI),每组8只。基础组饲基础饲料,其他两组饲高脂饲料。在饲喂饲料的同时,各组灌胃给相应干预剂。在0、3、6周尾静脉采血,测甘油三酯(TG)、胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)水平。6周末留取胸主动脉组织。酶法测TG、TC、HDL-C水平,反转录聚合酶链反应(RT-PCR)测PPARγ mRNA表达,电泳迁移率变动分析(EMSA)测NF-κB活性。结果①HL组与C组相比,血清TG、TC含量明显升高(P<0.05),PI组较HL组明显降低(P<0.05),PI组与C组间差异无统计学意义。②HL组胸主动脉壁PPARγ mRNA表达较C组降低(P<0.05),NF-κB活性明显升高。③PI组主动脉壁PPARγ mRNA表达较HL组明显升高(P<0.05),NF-κB活性明显降低。结论吡格列酮具有降低血清TG、TC的作用;吡格列酮能通过上调高脂状态下大鼠胸主动脉壁PPARγ mRNA表达,抑制NF-κB激活。     

益生菌对大鼠血脂和免疫功能影响的实验研究

目的 研究益生菌对大鼠血脂和免疫功能的影响.方法 用高脂饲料喂养大鼠,以洛伐他汀阳性对照物,以不同种益生菌喂养实验组大鼠,在实验开始前和实验开始后30 d时检测各组大鼠血清TC、TG和免疫指标,与对照组比较.结果 益生菌喂养组大鼠与对照组大鼠比较,益生菌喂养组大鼠血中TC及TG均明显低于对照组(P＜0.01),免疫指标明显高于对照组(P＜0.05).结论 益生菌明显降低益生菌喂养组大鼠血中的TC、TG,而且提高益生菌喂养组大鼠的免疫功能.     

普罗布考对动脉粥样硬化大鼠血管活性物质的影响

目的 探讨普罗布考对动脉粥样硬化(AS)大鼠血管活性物质的影响.方法 60只SD大鼠随机均分为对照组(A组)、高脂饲料+维生素D3(VitD3)组(B组)、高脂饲料组(C组)、高脂饲料+普罗布考+VitD3组(D组)、高脂饲料+普罗布考组(E组).第12周时对大鼠取血检测血清甘油三酯(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、空腹血糖(FBG)、空腹胰岛素(FIns)、一氧化氮(NO)、一氧化氮合酶(NOS)、超氧阴离子(O2-)和超氧化物歧化酶(SOD);并计算胰岛素抵抗指数(HOMA-IR),免疫组化法检测基质金属蛋白酶9(MMP-9)表达.结果 与A组相比,B、C组TG、TC、LDL-C、NO、NOS、O2-、FBG、FIns、HOMA-IR水平以及MMP-9表达增加(P＜0.01),HDL-C水平降低(P＜0.01);而普罗布考干预后NO、NOS水平升高(P＜0.05),TC、HDL-C、LDL-C、O2-水平以及MMP-9表达减少(P＜0.05),TG、SOD、FBG、FIns、HOMA-IR水平无统计学差异(P＞0.05).结论 普罗布考通过抑制炎症反应,减少活性氧簇的生成,进而改善AS大鼠的血管内皮功能.     

Quantitative in vivo and in vitro sex differences in artemisinin metabolism in rat

1. The pharmacokinetics of the antimalarial compound artemisinin were compared in the male and female Sprague-Dawley rat after single dose i.v. (20 mg.kg) or i.p. (50 mg.kg) administration of an emulsion formulation. 2. Plasma clearance of artemisinin was 12.0 (95% confidence interval: 10.4, 13.0) l.h. kg in the male rat and 10.6 (95% CI: 7.5, 15.0) l.h. kg in the female rat suggesting high hepatic extraction in combination with erythrocyte uptake or clearance. Artemisinin half-life was 0.5 h after both routes of administration in both sexes. Values for plasma clearance and half-lives did not statistically differ between the sexes. 3. After i.p. administration artemisinin AUCs were 2-fold higher in the female compared with male rat (p 0.001). Artemisinin disappearance was 3.9-fold greater in microsomes from male compared with female livers and it was inhibited in male microsomes by goat or rabbit serum containing antibodies against CYP2C11 and CYP3A2 but not CYP2B1 or CYP2E1. 4. The unbound fraction of artemisinin in plasma was lower (p 0.001) in plasma obtained from the male (8.8 2.0%) compared with the female rat (11.7 2.2%). 5. The possibility of a marked sex difference, dependent on the route of administration, has to be taken into account in the design and interpretation of toxicological studies of artemisinin in this species.     

Quantitative in vivo and in vitro sex differences in artemisinin metabolism in rat

1. The pharmacokinetics of the antimalarial compound artemisinin were compared in the male and female Sprague-Dawley rat after single dose i.v. (20 mg x kg(-1)) or i.p. (50 mg x kg(-1)) administration of an emulsion formulation. 2. Plasma clearance of artemisinin was 12.0 (95% confidence interval: 10.4, 13.0) 1 x h(-1) x kg(-1) in the male rat and 10.6 (95% CI: 7.5, 15.0) 1 x h(-1) x kg(-1) in the female rat suggesting high hepatic extraction in combination with erythrocyte uptake or clearance. Artemisinin half-life was approximately 0.5 h after both routes of administration in both sexes. Values for plasma clearance and half-lives did not statistically differ between the sexes. 3. After i.p. administration artemisinin AUCs were 2-fold higher in the female compared with male rat (p < 0.001). Artemisinin disappearance was 3.9-fold greater in microsomes from male compared with female livers and it was inhibited in male microsomes by goat or rabbit serum containing antibodies against CYP2C11 and CYP3A2 but not CYP2B1 or CYP2E1. 4. The unbound fraction of artemisinin in plasma was lower (p < 0.001) in plasma obtained from the male (8.8 +/- 2.0%) compared with the female rat (11.7 +/- 2.2%). 5. The possibility of a marked sex difference, dependent on the route of administration, has to be taken into account in the design and interpretation of toxicological studies of artemisinin in this species.     

Interindividual variability in metabolic activation in humans in vivo

In assessing interindividual variability in metabolic activation, the toxic metabolite is often too unstable for conventional analysis. Possible alternatives include a stable product of the reactive metabolite e.g. cysteinyl derivatives of N-acetyl-4-benzoquinoneimine, the toxic metabolite of paracetamol, adducts with DNA or protein, and indirect measurement of the activity of the enzyme(s) producing the active metabolite. An example of the last approach is the use of furafylline, a highly specific inhibitor of human CYP1A2, to determine the extent of the metabolic activation of the cooked food mutagens PhIP and MeIQx. The extent of inhibition, determined from levels of unchanged amine in urine, is an indirect measure of the activity of the activation pathway. Further refinement of this approach, allied to improved measures of the biological process of interest should prove of value in evaluating interindividual variability and its role in the risk assessment process.     

Theophylline kinetics in peripheral tissues in vivo in humans

Several biochemical and cellular effects have been described for methylxanthines under in vitro conditions. However, it is unknown, whether threshold concentrations required to exert these effects are attained in target tissues in vivo. We therefore employed the microdialysis technique for measuring theophylline concentrations in peripheral tissues under in vivo conditions.Following in vitro and in vivo calibration, microdialysis probes were inserted into the medial vastus muscle and into the periumbilical subcutaneous adipose layer of healthy volunteers. Following single oral dose administration of 300 mg or i.v. infusion of 240 mg theophylline, in vivo time courses of theophylline concentrations were monitored in tissues and plasma. Major pharmacokinetic parameters (c_max, t_max, AUC) were calculated for plasma and tissue time courses. The mean AUC_tissue /AUC_plasma-ratio was 0.56 (p.o.) and 0.55 (i.v.) for muscle and 0.55 (p.o.) and 0.72 (i.v.) for subcutaneous adipose tissue.We conclude that microdialysis provides important information on the distribution and the tissue pharmacokinetics of theophylline.Abbreviations FPIA Fluorescence polarisation immuno assay - AUC Area under the curve - t_max Time to peak concentration - c_max Peak concentration     

休克时血中氧自由基的变化

本实验测定10名休克患者血浆和红细胞的丙二醛(MDA)、血浆总抗的氧化活性(AOA)的含量。结果表明:休克病人红细胞膜和血浆 MDA 含量(4.298±0.722;5.348±0.834)与对照组(3.235±0.682;4.356±1.081)比较明显增高(P<0.05);血浆 AOA(39.65±7.858)与对照组(48.21±10.81)比较明显降低(P<0.01)。提示:休克时,患者机体内自由基反应增强是引起组织细胞损伤的原因之一。     

Changes in angiopoietin expression in glomeruli involved in glomerulosclerosis in rats with daunorubicin-induced nephrosis

AIM: To study the potential pathological role of endogenous angiopoietins in daunorubicin-induced progressive glomerulosclerosis in rats. METHODS: Seventy male Wistar rats were allocated randomly into a daunorubicin group (DRB; n=40) or a control group (n=30). The rats in the DRB group were injected with DRB (15 mg/kg), in their tails. Subsequently, at intervals of 1, 2, 4, 6, 8, and 12 weeks, 5 male Wistar rats in each group were chosen randomly for 24 h urinary protein quantitative measurements (24 h UPQM), and determination of plasma tumor necrosis factor alpha (TNF-alpha), angiopoietin-1 (Ang1), and angiopoietin-2 (Ang2) levels. Kidney sections were examined by electron microscopy, Periodic Acid Schiff (PAS) staining, immunohistochemical staining and in situ hybridization histochemistry. RESULTS: As glomerulosclerosis progressed in the DRB group, expression of Ang1 mRNA and protein in glomeruli decreased and expression of TNF-alpha protein, Ang2 mRNA and protein in glomeruli increased. Expression of Ang1 mRNA and protein in glomeruli were negatively correlated with 24 h UPQM, Fn protein expression, and mean area of extracellular matrix (MAECM). In comparison, expression of Ang2 mRNA and protein in glomeruli were positively correlated with 24 h UPQM, Fn protein expression and MAECM; furthermore, there was a positive correlation between plasma Ang2 and 24 h UPQM. Plasma TNF-alpha and expression of TNF-alpha in glomeruli were positively correlated with expression of Ang2 mRNA and protein in glomeruli. There was a negative correlation between Ang1 protein expression and Ang2 protein expression in glomeruli. CONCLUSION: During DRB-induced glomerulosclerosis, podocyte injury led to a shift in the balance of Ang1 and Ang2 in glomeruli. Increased TNF-alpha in plasma and glomeruli may upregulate Ang2 expression in glomeruli. Elevated Ang2 in both plasma and glomeruli may mediate protein permeability through the glomerular filtration barrier. Moreover, local expression of Ang2 may facilitate the progress of glomerulosclerosis by upregulating a component expression of extracellular matrix.     

Trichinellosis in immigrants in Switzerland

We describe a case of trichinellosis diagnosed at the Division of Infectious Diseases, Hospital of Lugano, in January 2009. This case was associated with a cluster of cases and was traced to the consumption of contaminated meat after a wild boar hunt in Bosnia.