昆布多糖对大鼠减肥及降血脂作用的实验研究

目的研究昆布多糖(Thallus laminariae polysaccharides,TLP)对大鼠减肥、降血脂的作用及其机制。方法制作肥胖大鼠模型,随机分成六组,分别以蒸馏水、TLP(100,200,300mg·kg^-1·d^-1)、奥利司他(orlistat,赛尼可,60mg·kg^-1·d^-1)和洛伐他汀(lovastatin,10mg·kg^-1·d^-1)灌胃,为期40d,在实验过程中,按时检测相关指标。结果TLP能明显降低肥胖大鼠的体重、减少大鼠腹腔、肾、生殖器周围脂肪、降低Lee’s指数和肝、肾重量(P<0.05),而且其作用与减肥药赛尼可在统计学上无显著性差异(P>0.05)。TLP能明显降低肥胖大鼠血清三酰甘油(TG)、胆固醇(TC)、提高高密度脂蛋白胆固醇(HDL-C)水平(P<0.05),而在实验期内低密度脂蛋白胆固醇(LDL-C)变化不明显(P>0.05),而且其作用与降脂药洛伐他汀比较无显著性差异(P>0.05)。TLP能明显改善肥胖大鼠血清卵磷脂胆固醇脂酰基转移酶(LCAT)、脂蛋白脂酶(LPL)和胰脂肪酶(PL)活性(P<0.05),而对肝脂肪酶(HL)活性在实验期间影响不明显(P>0.05)。结论TLP对肥胖大鼠具有明显的减肥作用,该作用与常用的减肥药赛尼可比较无显著性差异。TLP同时能降低血清甘油三酯和总胆固醇、改善血清HDL-C水平,而且该作用与降脂药洛伐他汀比较无显著差异。其作用机制可能与增强LCAT、LPL、PL酶活性有关。     

多廿醇对高脂血症大鼠脂蛋白代谢关键酶活性的影响

目的:研究多廿醇的降胆固醇作用及其酶学机制。方法:将大鼠随机分为对照组、多廿醇(4.0mg·kg-1·d-1)预防组、多廿醇低、中、高剂量(4.0、6.0、8.0mg·kg-1·d-1)组、阳性药洛伐他汀组和高脂模型组(后5组先行高脂造模4周),灌胃给药6周后采集血液,测定血清中总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)含量;称量大鼠体质量、肝重,计算肝脏系数;测定血清卵磷脂胆固醇酰基转移酶(LCAT)、肝脏脂蛋白脂酶(LPL)和肝脂酶(HL)活性。结果:多廿醇各组能明显降低高脂模型大鼠TC39.1%～43.3%(P<0.01)、LDL-C66.6%～80.7%(P<0.01)、肝脏系数11.1%～11.8%(P<0.01);高剂量组升高HDL-C14.0%(P<0.05),中、高剂量组LCAT活性分别升高41.9%、44.3%(P<0.01),HL活性分别升高20.0%(P<0.05)、28.0%(P<0.01)。结论:多廿醇对高脂模型大鼠具有明显降胆固醇作用,其作用可能与升高脂蛋白代谢关键酶的活性有关。     

加味苓桂术甘汤对奥氮平诱导肥胖大鼠的减肥作用

目的:探讨加味苓桂术甘汤(LGSG)对抗精神病药奥氮平(olanzapine)诱导肥胖大鼠的减肥作用。方法:SD雌性大鼠70只,按体质量随机分为正常对照组10只,其余60只灌胃给予奥氮平(1.2mg.kg-1.d-1)2周。将造模成功的40只肥胖大鼠随机分为模型组、盐酸西布曲明组(2.5mg.kg-1.d-1)、加味苓桂术甘汤低(4.5g.kg-1.d-1)、高(9.0g.kg-1.d-1)剂量组,每组10只。动物继续给予奥氮平处理,同时灌胃给予上述药物处理5周,并于药物处理结束时测定大鼠体质量、Lee’s指数、肾和子宫周围脂肪垫湿重、脂肪系数、血脂的变化。结果:加味苓桂术甘汤处理肥胖大鼠5周后,饮食量和体质量明显低于模型组大鼠,脂肪湿重和脂肪系数明显减少(P<0.05或P<0.01),血清游离脂肪酸(FFA)明显减少(P<0.05或P<0.01),高密度脂蛋白胆固醇(HDL-C)明显增加(P<0.05或P<0.01),其中加味苓桂术甘汤高剂量还能明显降低肥胖大鼠的Lee’s指数(P<0.05)。结论:加味苓桂术甘汤对奥氮平诱导的肥胖大鼠具有降低体质量,抑制肥胖,调节血脂的作用,其作用可能与减少动物摄食,增加...     

玉米须总皂苷对肥胖大鼠脂肪组织中过氧化物酶体增殖物激活受体γ和细胞死亡诱导DFFA样效应蛋白A表达的影响

目的探讨分析玉米须总皂苷对高脂饮食诱导的肥胖大鼠血脂是否有调节作用,并研究其脂肪组织中过氧化物酶体增殖物激活受体(PPAR)γ和细胞死亡诱导DFFA样效应蛋白A(CIDEA)的表达特点。方法将40只SPF级SD雄性大鼠按随机数字表法分为正常对照组(正常饮食+1mL·kg-1·d-10.9%氯化钠注射液灌胃)、模型对照组(高脂饮食+1mL·kg-1·d-1 0.9%氯化钠注射液灌胃)、玉米须总皂苷低剂量治疗组(高脂饮食+100mg·kg-1·d-1玉米须总皂苷灌胃)和玉米须总皂苷高剂量(高脂饮食+200mg·kg-1·d-1玉米须总皂苷灌胃),高脂饮食12周造模,治疗12周后,称量大鼠体质量,检测血清总胆固醇、甘油三酯、低密度脂蛋白胆固醇(LDL-C)和高密度脂蛋白胆固醇(HDL-C)的变化特点,苏木精-伊红(HE)染色观察脂肪细胞病理学,实时荧光定量聚合酶链反应和蛋白质印迹法检测脂肪组织中PPARγ和CIDEA的表达特点。结果在整个治疗期间,各组大鼠精神活动和日常情况并没有明显差异;从治疗开始,模型对照组大鼠体质量就明显高于正常对照组(P<0.05),玉米须总皂苷治疗4周后开始逐渐降低,直到治疗12周后玉米须总皂苷低剂量和高剂量组则明显低于模型对照组(P<0.05);与正常对照组相比,模型对照组甘油三酯、总胆固醇和HDL-C明显升高(P<0.05),LDL-C明显降低(P<0.05);与模型对照组相比,玉米须总皂苷治疗后甘油三酯、总胆固醇和HDL-C明显降低(P<0.05),而LDL-C则明显升高(P<0.05);HE染色正常组脂肪细胞大小均一,模型组脂肪细胞明显膨胀,而玉米须总皂苷治疗后,脂肪颗粒明显缩小;与正常对照组相比,模型对照组大鼠脂肪组织中PPARγ和CIDEA蛋白和mRNA表达明显降低(P<0.05),与模型对照组相比,玉米须总皂苷治疗后PPARγ和CIDEA明显升高(P<0.05)。结论玉米须总皂苷对高脂饮食诱导的肥胖大鼠体质量具有明显的降低作用,其作用机制可能是通过提高脂肪组织中PPARγ和CIDEA的表达实现的。     

三氧化二砷对大鼠睾丸细胞酶的作用

目的:探讨药理浓度的三氧化二砷(As2O3)对雄性大鼠血清睾丸酶及精子生成的影响.方法:不同剂量的As2O3(2mg·kg-1·d-1,4 mg·kg-1·d-1和8 mg·kg-1·d-1)给予大鼠腹腔内注射,2周后检测大鼠血清睾丸酶的含量,同时,测定大鼠血清砷的含量、睾丸脏器系数、睾丸精子头计数,并计算每日精子生成量.结果:中剂量组各种酶都有所下降,G-6-PD、LDH及LDH-X的减少有统计学意义(P＜0.01,P＜0.01和P＜0.05);大剂量组ACP、ALP、G-6-PD、LDH及LDH-X均明显下降(P＜0.01).随着给大鼠腹腔注射的As2O3浓度增加,血中砷浓度明显增加(P＜0.01).3种剂量组的睾丸脏器系数与对照组差异均无显著性(P＞0.05),大剂量组睾丸精子头数和每克睾丸每日精子生成量与对照组比较减少明显(P＜0.01),血清砷含量与大鼠精子头数之间呈直线负相关(r=-0.515,P＜0.01).结论:As2O3对睾丸酶的抑制,影响了睾丸精子的生成而导致雄性生殖毒性.     

苯妥英锌对家兔血清高密度脂蛋白胆固醇的影响

目的:研究家免口服苯妥英锌(PHTZ)对血清高密度脂蛋白胆固醇(HDL-C)的影响.方法:家兔分别口服PHTZ和苯妥英钠(PHTS)30d(剂量分别为:6,12,24mg·kg-1·d-1),用酶法测定血清中总胆固醇(TC)和三酰甘油(TG)的含量,HDL-C的测定采用磷钨酸镁盐沉淀后同TC测定法,低密度脂蛋白胆固醇(LDL-C)用费氏(Friedeuald)公式计算.用原子吸收分光光度法测定服药前后血清及服药后肝中Zn和Cu浓度.结果:PHTZ高、中剂量组分别使血清HDL-C升高76.0%(P＜0.01)和52.1%(P＜0.01),LDL-C分别降低19.7%(P＞0.05)和16.6%(P＞0.05),对TC和TG无显著影响.PHTZ使血清HDL-C升高的ED50为12.7mg·kg-1,PHTS使血清HDL-C提高的ED50为23.7mg·kg-1.PHTZ中剂量组使血清Zn浓度下降29.2%,与血清HDL-C上升的百分数呈负相关(r=-0.303 5,P＞0.05),使肝脏Zn浓度上升56.2%,与血清HDL-C上升的百分数呈正相关(r=0.726 3,P＜0.05),血清和肝脏中Cu无显著变化.结论:PHTZ使家兔血清HDL-C升高比PHTS更明显,ED50比PHTS低,可能与分子结构中的Zn有关.     

高胆固醇血症患者服用他汀类药物后血清触珠蛋白水平变化的初步研究

目的:分析高胆固醇血症患者服用他汀类调脂药前后血清触珠蛋白(haptoglobin,Hp)水平的变化,探讨其与他汀类药物治疗的关系和临床意义。方法:入组原发性高胆固醇血症患者32例,分别服用洛伐他汀/烟酸缓释片(10 mg/500 mg.d-1)和匹伐他汀(2 mg.d-1),治疗8周后,观察药前、药后血清Hp水平的变化。结果:高胆固醇血症患者分别服用2种他汀类调脂药物后,两组Hp水平均高于治疗前(P<0.05)。其中,服用洛伐他汀/烟酸缓释片的患者,Hp增加了17.87%;服用匹伐他汀的患者,Hp增加了19%。结论:服用他汀药物后,高胆固醇血症患者的血清Hp水平增加。     

西布曲明对谷氨酸钠诱导的肥胖动物模型的影响

目的　评价西布曲明 (Sibutramine ,Meridia ,MR)对肥胖动物的减肥作用。方法　取刚出生d 1的大鼠 ,♀♂兼用 ,皮下注射谷氨酸钠 (MSG) 3mg·g-1·d-1,连续 5d ;以诱导动物产生肥胖。在造型后 2 1d ,将肥胖动物按体重随机均分为 5组 ,分别灌胃MR 2 0、4 0和 8 0mg·kg-1·d-1;安菲拉酮 6 0mg·kg-1·d-1,模型组和对照组则均给 0 5 %CMC10ml·kg-1·d-1,连续 2 8d。在实验结束时 ,取样检测各指标。结果　研究显示 ,MR可使MSG诱导的肥胖大鼠体重增加减慢 ,使其脂肪垫重量及其Lees指数减少 ,脂肪细胞直径变小 ,脂肪细胞数 (一个视野内 )增加 ,使MSG大鼠血清甘油三酯降低 ,使其在禁食状态下降低的血糖及胰岛素水平恢复正常。MR对MSG的作用主要是降低其TG水平 ,而对TC无明显作用。结论　试验结果显示MR具有调节和改善脂质代谢及明显的减肥作用     

荷丹片对动脉粥样硬化大鼠氧化应激的影响

目的:观察不同剂量荷丹片对动脉粥样硬化大鼠氧化应激的影响。方法:48只雄性SD大鼠随机分为正常组,模型组,荷丹片高(3g·kg-1·d-1)、中(1.5g·kg-1·d-1)、低(0.5g·kg-1·d-1)剂量组及辛伐他汀组,每组8只。正常组给予普通鼠饲料喂养,其余各组使用高脂饲料造模。12周后取各组大鼠腹主动脉电子显微镜下观察主动脉形态学变化;腹静脉取血测定各组大鼠超氧化物歧化酶(SOD)、丙二醛(MDA)及NO含量。结果:高剂量荷丹片可以升高血清SOD、NO水平,降低血清MDA水平,与模型组相比差异有统计学意义(P0.05)。荷丹片高剂量组与辛伐他汀组比较差异无统计学意义(P0.05)。荷丹片组镜下表现主动脉粥样硬化组织损伤明显减轻。结论:高剂量荷丹片通过减轻AS大鼠氧化应激发挥其抗动脉粥样硬化的作用。     

生姜有效部位的调血脂作用研究

目的　观察生姜有效部位对高脂血症大鼠血脂水平的影响。方法　建立大鼠高脂血症模型,以洛伐他汀做阳性对照,分别每日灌服生姜有效部位2 0 0mg·kg-1、4 0 0mg·kg-1、80 0mg·kg-1,测定大鼠血清总胆固醇(TC)、甘油三酯(TG)和高密度脂蛋白胆固醇(HDL -C)水平。结果　生姜有效部位能显著降低血清TG、LDL -C,升高HDL -C水平。结论　生姜有效部位具有调血脂作用。     

Affective and Anxiety Disorders and Alcohol and Drug Dependence:

Depression and anxiety frequently coexist in patients with substance use disorders. This clinically-oriented article examiens the relationship between these conditions and emphasizes data showing that substances of abuse can cause signs and symptoms of both depression and anxiety. These substance-related syndromes appear to have a different course and prognosis than uncomplicated, independent anxiety and major depressive disorders, and clinicians should consider the role of alcohol and other drugs in all patients presenting with these complaints. The authors will also outline an approach for diagnosing and managing patients with the combination of a substance use and depressive or anxiety disorder.     

Modelling and simulation of variability and uncertainty in toxicokinetics and pharmacokinetics

Two important methodological issues within the framework of the variability and uncertainty analysis of toxicokinetic and pharmacokinetic systems are discussed: (i) modelling and simulation of the existing physiologic variability in a population; and (ii) modelling and simulation of variability and uncertainty when there is insufficient or not well defined (e.g. small sample, semiquantitative, qualitative and vague) information available. Physiologically based pharmacokinetic models are especially suited for separating and characterising the physiologic variability from the overall variability and uncertainty in the system. Monte Carlo sampling should draw from multivariate distributions, which reflect all levels of existing dependencies in the intact organism. The population characteristics should be taken into account. A fuzzy simulation approach is proposed to model variability and uncertainty when there is semiquantitative, qualitative and vague information about the model parameters and their statistical distributions cannot be defined reliably.     

成骨细胞的功能与损伤和骨质疏松的防治

骨质疏松是一种全身性骨骼疾病,导致骨折风险增加。成人的骨量通过破骨细胞的骨吸收和成骨细胞的骨形成作用来维持动态平衡,治疗骨质疏松症的理想策略是抑制破骨细胞的骨吸收和/或增强成骨细胞的骨形成功能。目前针对保护成骨细胞及增强其功能的骨质疏松疗法相对较少。因此,本文针对成骨细胞相关功能蛋白、各种细胞损伤机制（内质网应激、氧化应激、机械过载、微小RNA和长链非编码RNA的影响等）及骨质疏松的治疗与预防作一综述,以期为针对增强成骨细胞功能的骨质疏松治疗策略提供新思路。     

Antiinfective and encrustation-inhibiting materials--myth and facts

Catheters, urethral and ureteral stents and other urological implants are frequently affected by encrustration and infection due to their permanent contact with urine. Indwelling urinary catheters provide a haven for microorganisms and thus require extensive monitoring. Several surface modification techniques have been proposed to improve the performance of devices including the immobilization of biomolecules, the incorporation of hydrophilic grafts to reduce protein adsorption, the creation of hydrophobic surfaces, the creation of microdomains to regulate cellular and protein adhesion, new polymers and antimicrobial coatings. Physico-chemical explanation to elucidate the mechanism of such encrustation or infection inhibiting materials is still not available. Our series of experiments showed a marked decrease of silver-activity in biological fluids which corresponds with the controversial clinical results obtained with silver coated urinary catheters. Rifampicin/minocycline coated catheters had very low activity against Gram-negative rods, enterococci and Candida spp., the main causing organisms of urinary catheter infection. Surface engineered materials and antimicrobial drug delivery systems will be the next generation of sophisticated urinary catheters and stents, if both efficacy as well as efficiency has been proved clinically.     

益生菌与肿瘤防治

益生菌广泛存在于自然界中,通过维持宿主体内菌群平衡、影响肠屏障功能和调节免疫应答等作用,提高宿主健康水平,被公认为"肠道健康卫士".一些益生菌可以增强机体的免疫功能,抑制致癌物质,影响肿瘤细胞的基因表达,对肿瘤具有拮抗作用.大量研究表明,益生菌在未来的肿瘤防治中有很好的应用和发展前景.     

Synthesis and anti-nociceptive and anti-inflammatory effects of gaultherin and its analogs

The synthesis of gaultherin (1) and its analogs was carried out to provide 11 glycosides under phase-transfer catalytic conditions. The activities of all synthesized compounds were evaluated by nitric oxide production inhibitory assay in vitro. Methyl 2-O-(4-O-β-d-galactopyranosyl)-β-d-glucopyranosylbenzoate (5f) showed significantly anti-nociceptive and anti-inflammatory effects by the evaluation in vivo. Structure–activity relationships within these compounds were discussed.     

Interaction of estrone and estradiol with DNA and protein of liver and kidney in rat and hamster in vivo and in vitro

[6,7-³H] Estrone (E) and [6,7-³H]estradiol-17 (E₂) have been synthesized by reduction of 6-dehydroestrone and 6-dehydroestradiol with tritium gas. Tritiated E and E₂ were administered by oral gavage to female rats and to male and female hamsters on a dose level of about 300 g/kg (54 mCi/kg). After 8 h, the liver was excised from the rats; liver and kidneys were taken from the hamsters. DNA was purified either directly from an organ homogenate or via chromatin. The radioactivity in the DNA was expressed in the units of the Covalent Binding Index, CBI = (mol chemical bound per mol DNA-P)/(mmol chemical administered per kg b.w.). Rat liver DNA isolated via chromatin exhibited the very low values of 0.08 and 0.09 for E and E₂, respectively. The respective figures in hamster liver were 0.08 and 0.11 in females and 0.21 and 0.18 in the males. DNA isolated from the kidney revealed a detectable radioactivity only in the female, with values of 0.03 and 0.05 for E and E₂, respectively. The values for male hamster kidney were < 0.01 for both hormones. The minute radioactivity detectable in the DNA samples does not represent covalent binding to DNA, however, as indicated by two sets of control experiments. (A) Analysis by HPLC of the nucleosides prepared by enzyme digest of liver DNA isolated directly or via chromatin did not reveal any consistent peak which could have been attributed to a nucleoside-steroid adduct. (B) All DNA radioactivity could be due to protein contaminations, because the specific activity of chromatin protein was determined to be more than 3,000 times higher than of DNA. The high affinity of the hormone to protein was also demonstrated by in vitro incubations, where it could be shown that the specific activity of DNA and protein was essentially proportional to the concentration of radiolabelled hormone in the organ homogenate, regardless of whether the animal was treated or whether the hormone was added in vitro to the homogenate.Carcinogens acting by covalent DNA binding can be classified according to potency on the basis of the Covalent Binding Index. Values of 10³–10⁴ have been found for potent, 10² for moderate, and 1–10 for weak carcinogens. Since estrone is moderately carcinogenic for the kidney of the male hamster, a CBI of about 100 would be expected. The actually measured limit of detection of 0.01 places covalent DNA binding among the highly unlikely mechanisms of action. Similar considerations can be made for the liver where any true covalent DNA binding must be below a level of 0.01. It is concluded that an observable tumor induction by estrone or estradiol is unlikely to be due to DNA binding.Paper presented at the Satellite Symposium of the European Society of Toxicology, Rome, March 29, 1983     

Acamprosate and naltrexone treatment effects on ethanol and sucrose seeking and intake in ethanol-dependent and nondependent rats

Rationale  Two pharmacotherapies are approved for treating alcohol craving (acamprosate and naltrexone), but both have shown mixed findings in animals and humans. Objectives  The present experiments utilized a “reinforcer blocking” approach (i.e., rats were able to consume ethanol during treatment) to better understand the efficacy of these treatments for ethanol seeking and drinking using ethanol-dependent and nondependent rats. Materials and methods  In “nondependent” experiments, drugs (acamprosate 50, 100, and 200 mg/kg; naltrexone 0.1, 0.3, and 1.0 mg/kg) were administered over 3-week periods prior to operant sessions with a low response requirement to gain access to reinforcers for 20 min. For “dependent” experiments, rats were made dependent in vapor/inhalation chambers. Results  Acamprosate and naltrexone had similar effects on intake in nondependent and dependent rats; neither drug was selective for ethanol over sucrose drinking. In nondependent animals, naltrexone was more efficacious at more doses than acamprosate, and acamprosate’s effects were limited to a dose that also had adverse effects on body weight. Both pharmacotherapies showed more selectivity when examining reinforcer seeking. In nondependent rats, acamprosate and naltrexone had response-attenuating effects in ethanol, but not sucrose, groups. In dependent animals, acamprosate had selective effects limited to a decrease in sucrose seeking. Naltrexone, however, selectively decreased ethanol-seeking in nondependent rats. Conclusions  The naltrexone-induced decreases in seeking suggested a change in incentive motivation which was selective for ethanol in nondependent rats. The “nondependent” paradigm may model early stages of “problem drinking” in humans, and the findings suggest that naltrexone could be a good intervention for this level of alcohol abuse and relapse prevention.     

Isolation and characterization of glycosylated and non-glycosylated prolactins from alligator and crocodile

Two molecular forms of prolactin (PRL). glycosylated and non-glycosylated, were isolated from pituitary glands of two reptiles, alligator and crocodile. The reptilian PRLs were extracted under alkaline conditions from the precipitate obtained after pituitaries were first extracted with 0.25 m sucrose, 1 mM NH₄HCO₃, pH 6.3. Purification was performed by ion exchange chromatography on DE-52, gel filtration on Sephadex G-75 superfine, and reversed phase high performance liquid chromatography. Two forms of both alligator and crocodile PRL, designated PRLI and PRLII, with molecular weights of 26000 and 24000 were isolated. Alligator and crocodile PRLI and PRLII were stained specifically in immunoblots with anti-sea turtle PRL and anti-ostrich PRL. Sequence analysis revealed that both forms of alligator and crocodile PRLs consisted of 199 amino acid residues with a glycosylation consensus sequence (Asn-Ala-Ser) at position 60 in alligator and crocodile PRLs with a molecular weight of 26000 (PRLI). In contrast, Thr was substituted for Asn at position 60 in the PRLs with a molecular weight of 24000 (PRLII). The sequences of alligator PRLs differed from crocodile PRLs only in position 134: Val for alligator PRLs and He for crocodile PRLs. There is a high degree of structural conservation between the reptilian PRLs isolated in this study and avian PRL; each showed 92% sequence identity with chicken PRL and 89% with turkey PRL.