枸杞子多糖及合并应用厌氧短棒杆菌菌苗对小鼠腹腔巨噬细胞抑制肿瘤增殖活性的影响(英文)

本研究观察了中药枸杞子(Lyciumbarbarum L.)提取物枸杞多糖(LBP)对小鼠腹腔巨噬细胞抑制肿瘤增殖活性的影响。结果表明,给正常小鼠ip LBP 40 mg/kg×7d能增强经Con A处理的巨噬细胞抑制肿瘤靶细胞增殖的活性;LBP 5.10.20,40mg/kg×7 d并与小剂量(250μg/只)厌氧短棒杆菌菌苗(Corynebacterium parvum,CP)合并应用,具有明显的协同效应。在LBP浓度为20 mg/kg时,效应最为显著,对靶细胞P815及P388增殖的抑制率分别为85.5％和63.6％;CP对照组则为28.1％及24.0％。表明合并应用LBP及CP可减少二者的用量,增强效应,减低CP的毒副作用。据本室先前的研究发现,LBP为主要作用于T细胞的免疫增强剂,能增强CTL,NK细胞的功能;CP则为巨噬细胞刺激剂。本研究结果提示,合并应用作用于免疫应答不同环节的免疫增强剂可获得协同效应,这将为临床肿瘤的免疫疗法中免疫增强剂的联合应用提供参考。此外,本实验还发现,来自经肿瘤细胞免疫小鼠的腹腔巨噬细胞,表现出较强的特异性抑制肿瘤增殖活性,LBP则能进一步加强其作用。以上结果提示,LBP无论对巨噬细胞在非特异性抗肿瘤或特异性抗肿瘤过程中,均具有激活作用。     

枸杞子多糖及合并应用厌氧短棒杆菌菌苗对小鼠腹腔巨噬细胞抑制肿瘤增殖活性

本研究观察了中药枸杞子（Lycium barbarumL.)提取物枸杞多糖（LBP）对小鼠腹腔巨噬细胞抑制肿瘤增殖活性的影响。结果表明，给正常小鼠ipLBP40mg/kg×7d能增强经ConA处理的巨噬细胞抑制肿瘤靶细胞增殖的活性；LBP5，10，20，40mg/kg×7d并与小剂量（250ug/只）厌氧短棒杆菌菌苗（Corynebacterium parvum,CP)合并应用，具有明显的协同效应，在LBP浓度为20mg/kg时，效应最为显著，对靶细胞P815及P388增殖的抑制率分别为85.5%和63.3%；CP对照组则为28.1%及240%，表明合并应用LBP及CP可减少二者的用量，增强效应，减低CP的毒副作用，据本室先前的研究发现，LBP为主要作用于T细胞的免疫增强剂，能增强CTL，NK细胞的功能；CP则为巨噬细胞刺激剂，本研究结果提示，合并应用作用于免疫应答不同环节的免疫增强剂可获得协同效主尖，这将为临床肿瘤的免疫疗法中免疫增强剂的联合应用提供参考，此外，本实验还发现，来自经肿瘤细胞免疫小鼠的腹腔巨噬细胞，表现出较强的特异性抑制肿瘤增殖活性，LBP则能进一步加强其作用。以上结果提示，LBP无论对巨噬细胞在非特异性抗肿瘤或特异性抗肿瘤过程中，均具有激活作用。     

肝康宁抗炎免疫作用研究

目的：研究肝康宁对炎症、免疫功能的影响。方法：取小鼠50只,随机分组,每日灌胃给药1次,连续5天,小鼠耳两面涂上药之后。分别称重观察左右耳片重量差值,表示肝胀炎症程度。结果：肝康宁能显著抑制二甲苯致小鼠耳肿胀及棉球肉芽肿增生,提高小鼠对碳粒的吞噬活性,明显增加小鼠溶血素抗体水平,增强DNCB诱发的DTH反应,促进ConAN激的小鼠淋巴细胞转化。结论：肝康宁具有抗炎及免疫增强作用。     

厚朴丸对小鼠胃肠活动的影响

目的:观察厚朴丸对小鼠胃排空和小肠推进运动的影响.方法:利用胃复安和阿托品造成小鼠胃排空亢进和胃排空抑制模型,利用新斯的明和肾上腺素造成小鼠小肠推进亢进和小肠推进抑制模型,观察厚朴丸对正常、亢进及抑制状态下小鼠胃肠活动的影响.结果:厚朴丸抑制正常小鼠胃排空和胃复安所致小鼠胃排空加快,能加强阿托品所致小鼠胃排空的抑制作用;对正常小鼠小肠推进和新斯的明所致小鼠小肠推进亢进也有抑制作用,但对肾上腺素所致小鼠小肠推进抑制无明显影响.结论:厚朴丸具有抑制正常和亢进状态的小鼠胃排空和小肠推进的作用,与临床用于止泻相符合.     

蒲薏颗粒对化疗荷瘤小鼠的增效减毒及免疫功能的影响

目的 研究蒲薏颗粒对荷瘤小鼠化疗增效、减毒及免疫调节作用。方法 建立小鼠恶性肿瘤转实体瘤模型,观察蒲薏颗粒与化疗药物合用对瘤体重量、血液白细胞(WBC)数、骨髓有核细胞数的影响;对肿瘤坏死因子(TNF-a)的影响以及对荷瘤小鼠免疫功能的影响。结果 蒲薏颗粒能增强化疗药物抑瘤作用、拮抗化疗药物对WBC及骨髓有核细胞的抑制;提高荷瘤小鼠TNF-a含量;增强免疫功能。结论 蒲薏颗粒对荷瘤小鼠具有化疗增效、减毒及免疫增强的作用。     

蒲薏颗粒对化疗荷瘤小鼠的增效减毒及免疫功能的影响

目的研究蒲薏颗粒对荷瘤小鼠化疗增效、减毒及免疫调节作用。方法建立小鼠恶性肿瘤转实体瘤模型,观察蒲薏颗粒与化疗药物合用对瘤体重量、血液白细胞（WBC）数、骨髓有核细胞数的影响;对肿瘤坏死因子（TNF-a）的影响以及对荷瘤小鼠免疫功能的影响。结果蒲薏颗粒能增强化疗药物抑瘤作用、拮抗化疗药物对WBC及骨髓有核细胞的抑制;提高荷瘤小鼠TNF-a含量;增强免疫功能。结论蒲薏颗粒对荷瘤小鼠具有化疗增效、减毒及免疫增强的作用。     

金桔胶囊抗炎镇痛、镇咳祛痰和免疫增强的药理学作用

目的:研究金桔胶囊抗炎镇痛、镇咳祛痰和免疫增强的药理学作用。方法:采用小鼠耳廓肿胀法和腹腔致炎法,观察金桔胶囊的抗炎作用;采用醋酸刺激扭体法复制小鼠疼痛模型,观察金桔胶囊的镇痛作用;采用氨水引咳法和酚红祛痰法观察金桔胶囊镇咳和祛痰作用;采用碳廓清法观察金桔胶囊对小鼠非特异性免疫功能的影响。结果:8.0、4.0 g/kg金桔胶囊能明显抑制二甲苯致小鼠耳廓炎性肿胀,延长小鼠扭体反应潜伏期、减少扭体次数,延长小鼠咳嗽潜伏期、减少咳嗽次数,增加小鼠气管的酚红排泌量(P<0.05),升高碳廓清指数及吞噬指数(P<0.05);8.0、4.0、2.0 g/kg金桔胶囊能降低醋酸致小鼠腹腔毛细血管通透性(P<0.01或P<0.05)。结论:金桔胶囊具有明显的抗炎镇痛、镇咳祛痰和免疫增强作用。     

愈疡胶囊对正常小鼠外周血和脾T淋巴细胞亚群的影响

目的：研究愈疡胶囊对正常小鼠外周血和脾T淋巴细胞亚群的影响.方法：24只雄性昆明小鼠,随机分为正常对照组、阳性对照组、愈疡胶囊高剂量组和愈疡胶囊低剂量组 分别灌胃蒸馏水及相应药物,流式细胞仪测定外周血和脾淋巴细胞T淋巴细胞亚群.结果：与正常对照组比较,给药组能明显升高小鼠外周血和脾淋巴细胞T淋巴细胞亚群CD4分子表达量（P〈0.01或P〈0.001）.结论：愈疡胶囊可增强正常小鼠的细胞免疫功能,为该药的免疫增强作用提供了实验依据.     

酵母葡聚糖的免疫活性

酵母葡聚糖(Yeast Glucan)是从酵母细胞壁提取的多种β-1,3葡聚糖的总称,在动物实验中表现出非特异性免疫增强作用。酵母葡聚糖能提高宿主对细菌、原虫、病毒以及真菌感染的抵抗力。用金黄色葡萄球菌攻击事先用酵母葡聚糖治疗的小鼠,其生存期延长。同样,酵母葡聚糖亦可延长金黄色葡萄球菌攻击的白血病小鼠及环磷酰胺给药小鼠的存活期。以上提示,酵母葡聚糖不但明显限制正常小鼠细菌感染过程,而且对由于赘生物或化疗造     

羊胎素-珍珠胶囊对小鼠免疫功能的影响

目的研究羊胎素-珍珠胶囊对动物的免疫增强作用。方法采用小鼠巨噬细胞吞噬功能试验和小鼠免疫器官重量系数测定，检测药物对小鼠血清溶血素的影响。结果羊胎素-珍珠胶囊能使小鼠免疫器官胸腺、脾脏重量明显增加，小鼠血清溶血素含量和单核吞噬细胞功能提高。结论羊胎素-珍珠胶囊具有明显免疫增强作用。     

Pulmonary vascular inflammation: effect of TLR signalling on angiopoietin/TIE regulation

Increased pulmonary vascular resistance is a critical complication in sepsis. Toll‐like receptor (TLR) as well as angiopoietin (ANG) signalling both contribute to the emergence of pulmonary arterial hypertension. We hypothesized that TLR stimulation by bacterial ligands directly affects expression and secretion of ligands and receptors of the angiopoietin/TIE axis. Microvascular endothelial (HPMEC) and smooth muscle cells (SMC) of pulmonary origin were incubated with thrombin and with ligands for TLR2, ‐4, ‐5, and ‐9. Expression and secretion of ANG1, ‐2, TIE2 and IL‐8 were determined using quantitative real‐time PCR and ELISA. TLR stimulation had no impact either on the expression of ANG2 and TIE2 in HPMEC or on that of ANG1 in SMC. However, overall levels of both released ANG1 and ‐2 were halved upon stimulation with the TLR9 ligand CpG, and ANG2 release was significantly enhanced by TLR4 activation when initially provoked by sequentially performed stimulation. Furthermore, enhanced ANG2 activity increased endothelial permeability, as demonstrated in an in vitro transwell assay. We conclude that sole TLR stimulation by bacterial ligands plays no significant role for altered expression and secretion of ANG1, ‐2 and TIE2 in human pulmonary vascular cells. The interplay between various stimuli is required to induce imbalances between ANG1 and ‐2.     

Antiobesity effect of <Emphasis Type="Italic">Tamarindus indica</Emphasis> L. pulp aqueous extract in high-fat diet-induced obese rats

Obesity and overweight are associated with atherosclerosis, fatty liver, hyperlipemia, diabetes mellitus, and various types of cancer. The global prevalence of overweight and obesity has reached epidemic proportions. Here, we investigated the effect of Tamarindus indica pulp aqueous extract (TIE) in diet-induced obese Sprague–Dawley rats. The animals were divided into five groups and labeled as follows: the normal control (NC) group received normal diet; the positive control (PC) group received high-fat diet; and the TIE 5, 25, and 50 groups, after the induction of obesity via a high-fat diet, received TIE at 5, 25, or 50 mg/kg orally for 10 weeks. It was observed that TIE decreased the levels of plasma total cholesterol, low-density lipoprotein (LDL), and triglyceride, and increased high-density lipoprotein (HDL), with the concomitant reduction of body weight. Moreover, TIE decreased plasma leptin and reduced fatty acid synthase (FAS) activity and enhanced the efficiency of the antioxidant defense system. TIE exhibits antiobesity effects, as indicated by a significant reduction in adipose tissue weights, as well as lowering the degree of hepatic steatosis in the obesity-induced rats. The extract possesses hepatoprotective activity, as it reversed the plasma liver enzymes level elevation prior to the high-fat diet. In conclusion, TIE improved obesity-related parameters in blood, liver, and adipose tissue in a rat model and suppressed obesity induced by a high-fat diet, possibly by regulating lipid metabolism and lowering plasma leptin and FAS levels. A dose-dependant effect of TIE is detected, where TIE at 50 mg/kg showed the most prominent effect, followed by TIE at 25 mg/kg and, subsequently, 5 mg/kg.     

Toxicity Reduction Evaluation, Toxicity Identification Evaluation and Toxicity Tracking in Direct Toxicity Assessment

Toxicity reduction evaluations (TREs) in the River Esk and Lower Tees Estuary were based on the approach described by USEPA, but adapted to tackle the specific problems of the two sites. A combination of toxicity tracking and toxicity identification evaluation (TIE) was used at both locations to enhance the understanding of source and type of toxicants present. The assessment of toxicity at Langholm focussed on pesticides present in the sewerage network. The TIE programme indicated that the most likely toxic agents within the effluent were the organophosphate pesticides diazinon and to lesser extent propetamphos, although these did not account for all of the observed toxicity. The exact source of these toxicants was not clear although toxicity tracking identified two potential candidates. The TRE undertaken on the discharge to the lower Tees utilised high-throughput methods with standard test organisms to generate toxicity information throughout a complex sewerage network. The toxicity tracking information was used in conjunction with TIEs to identify a number of key sources of toxicity. Substantial toxicity was associated with a currently untreated industrial effluent. Chemical analysis and TIE highlighted cyanide as the likely toxicant in this effluent and its possible significance in the final discharge.     

Sediment quality assessment survey and toxicity identification evaluation studies in Lavaca Bay, Texas, a marine Superfund site

A sediment quality assessment survey was conducted in Lavaca Bay, Texas, in proximity to a marine Superfund National Priority List (NPL) site. Previous studies at this site had focused primarily on the degree and extent of mercury contamination. The purpose of this survey was to determine the potential ecotoxicological impacts of contaminants, using sensitive sediment toxicity tests in conjunction with a comprehensive chemical analysis of the sediments. In addition, phase I toxicity identification evaluation (TIE) studies were conducted at several of the more toxic sites. Sea urchin (Arbacia punctulata) fertilization and embryological development tests with sediment pore water were employed to assess the toxicity of the sediments. Elevated levels of mercury were found in a number of samples as much as 10-20 times that of background. Six stations had total polycyclic aromatic hydrocarbon (PAH) concentration above the probable effect level (PEL) guideline value, and some stations had concentrations as much as 1000 times above background levels. Eighteen of the 24 stations exhibited toxicity in one of the toxicity tests, while 14 stations were toxic in both tests. A number of stations within the fish closure area exceeded 8-16 of the PEl guidelines. Both aeration and the C18 column treatments were effective in reducing toxicity from the pore water of the two stations included in the TIE. This information, in conjunction with the fact that two of the four stations with the highest mercury concentrations were not toxic, suggests that the toxicity observed in this study is primarily due to organics, probably PAHs, and not mercury. We recommend that these other contaminants of concern be considered in any remedial actions that are planned for this NPL site and that impacts on the ecosystem, as well as human health issues, also be considered.     

Tannery wastewater characterization and toxicity effects on Daphnia spp

Tannery wastewater contains large quantities of organic and inorganic compounds, including toxic substances such as sulfides and chromium salts. The evaluation of wastewater quality in Chile nowadays is based on chemical specific measurements and toxicity tests. The goal of this research was to characterize tannery wastewater and to relate its physical/chemical parameters with its acute toxicity effect on Daphnia pulex. To distinguish the most important toxic compounds, physical/chemical techniques were applied to a grab sample of a final effluent based on the Phase I toxicity identification evaluation (TIE) procedure. In addition, the toxicity of a beamhouse effluent after an activated sludge reactor treatment was investigated on Daphnia magna (introduced species) and D. pulex (native species). Effluent from different tannery processes (soaking, beamhouse, tanning and final) demonstrated high values of chemical organic demand (COD; 2840-27,600 mg L(-1)), chloride (1813-16,500 mg L(-1)), sulfate (230-35,200 mg L(-1)), and total solids (8600-87,100 mg L(-1)). All effluents showed extremely toxic effects on D. pulex, with 24-h mean lethal values (LC(50)) ranging from 0.36% to 3.61%. The Phase I TIE profile showed that toxicity was significantly reduced by air stripping, filtration, and a cationic exchange resin, with toxicity reductions ranging between 46% and 76%. The aerobically treated beamhouse effluent showed significantly less toxicity for both species (43%-74%). The chemical parameters demonstrated that the remaining toxicity of the treated beamhouse effluent was associated with its ammonia (120 mg N-NH(3) L(-1)) and chloride (11,300 mg Cl(-) L(-1)) contents.     

The endocrine disrupting effect of municipal effluent on the zebra mussel (Dreissena polymorpha)

Municipal effluents have been shown to contain a cocktail of endocrine disrupting chemicals (EDCs). The estrogenic effect of these effluents has been demonstrated on both vertebrate and invertebrate species by the feminisation of the exposed males. This effect was investigated on the freshwater zebra mussel (Dreissena polymorpha) after exposure to tertiary treated effluent from a municipal sewage treatment works (STW). Mussels were exposed to the effluent in situ for 112 days during gametogenesis (December to mid-March). Levels of vitellin (Vn)-like proteins (the major protein found in oocytes) were measured indirectly using the alkali-labile phosphate (ALP) technique and confirmed by gel electrophoresis. Significant increases (P < 0.05) in Vn-like proteins were found in both male and female mussels after exposure to the effluent, indicating that endocrine disruption (ED) had occurred. Using High-performance thin layer chromatography (HPTLC) levels of the mussels main steroid, cholesterol were found to more than double after effluent exposure. General physiological (survival, condition, etc.) and histological effects were also investigated. Histological effects observed included a large increase in interstitial tissue between the seminiferous tubules of the gonad in male mussels exposed to effluent. Effluent samples were tested for estrogenic compounds using the toxicity identification and evaluation method (TIE). A complex mixture of compounds with estrogenic activity was found with 17beta-estradiol, 17alpha-ethynlestradiol and bisphenol A accounting for the majority of the effluents estrogenic activity. Results indicate that the zebra mussel is a suitable bioindicator of endocrine disruption in freshwater environments.     

pH dependent toxicity of five metals to three marine organisms

The pH of natural marine systems is relatively stable; this may explain why metal toxicity changes with pH have not been well documented. However, changes in metal toxicity with pH in marine waters are of concern in toxicity testing. During porewater toxicity testing pH can change 1–2 units as porewater is transferred from in situ to a test container. These changes in pH may alter metal toxicity. Also, deliberately altering the sample pH is an important toxicity identification and evaluations (TIE) manipulation designed to detect changes in ammonia toxicity. If altering pH also changes metal toxicity, this may confound interpretation of TIE manipulation results. This study demonstrates that alteration of pH can also change the toxicity of Cu, Cd, Ni, Pb, and Zn to Mysidopsis bahia (mysid), Ampelisca abdita (amphipod) and Vibrio fischerii [Microtox solid phase test (MSP)]. Changes in toxicity with respect to pH were metal and organism specific with the following trends. For the MSP assay, as pH decreased there was a decrease in toxicity for Pb, Ni, Cd, and Zn and an increase in toxicity for Cu. For mysids, as pH decreased, there was a decrease in toxicity for Pb and an increase in toxicity for Cu and Ni. For amphipods, Cu was the only metal that showed decreased toxicity with decreasing pH; the toxicity of all other metals for amphipods remained constant. Results of this study indicate changes in metal toxicity with respect to pH must be considered for porewater testing and TIE interpretation. ©1999 John Wiley & Sons, Inc. Environ Toxicol 14: 235–240, 1999     

牛黄消炎片的质量标准研究

采用薄层色谱法（TLC）对牛黄消炎片中主要成分牛黄、大黄和蟾酥进行定性鉴别,应用紫外分光光度法对制剂中酯蟾毒配基的含量进行测定,以便控制其内在质量。     

Metabolism of 17alpha-ethynylestradiol by intact liver parenchymal cells isolated from mouse and rat

Liver parenchymal cells isolated by perfusion from female C3H/HeN-MTV+Nctr mice and Sprague-Dawley rats were incubated with [6,7-3H] 17alpha-ethynylestradiol (EE2). The incubates were individually fractionated into free steroid (organic phase), steroid conjugates (aqueous), and bound steroids (macromolecular pellet). The rat had significantly less total free radioactive steroid but significantly more total conjugated and irreversibly bound radioactivity than the mouse. However, when the metabolic conversion of EE2 was compared in the rat and the mouse on a cellular basis (metabolic clearance per 10(6) cells), the rat was found to be less efficient than the mouse. The two species were essentially equivalent in their covalent binding when expressed on a per 10(6) cell basis. Purification of the free radiolabeled steriods on LH-20 demonstrated the mouse to have the parent compound and on identifiable 2-OH-EE2 fraction. The rat had EE2 and an identifiable 2-methoxy-EE2 fraction. A major metabolite fraction for both species was very nonpolar and, although not identified, was found to be ethynylated as demonstrated by silver-sulfoethylcellulose chromatography. The conjugate fractions of the mouse were indicative of glucuronide conjugation, whereas the rat had additional conjugate fractions suggestive of sulfoconjugation.     

Effects of eicosanoids, neuromediators and bioactive peptides on murine airways

The effects of several mediators including prostanoids, neuromediators, bioactive peptides and leukotrienes were investigated on the trachea, upper bronchi, lower bronchi and lung parenchyma of selected strains of mice mounted in a cascade superfusion system. The upper airways (trachea, upper bronchi) responded with greater maxima than lower airways (lower bronchi, lung parenchyma). Acetylcholine, carbachol, serotonin and 9, 11-dideoxy-9alpha,11alpha-epoxymethano-prostaglandin F(2alpha)serotonin>/=acetylcholine. Prostaglandins E(2), F(2alpha) and D(2)90% relaxation in some cases. The rank order of potency for the prostaglandins was E(2)>/=F(2alpha)D(2) with the exception of the lower bronchi on which prostaglandins had the following order of potency: F(2alpha)>/=E(2)D(2). The effects of prostaglandins were similar in four commonly used strains of mice (CD-1, BALB/c, C57BL/c6 and C3H) with some variations in efficacy. Iloprost was a weak mouse airway relaxant. It had the greatest effect on the trachea and bronchi of BALB/c and C57BL/c6 mice, whereas it had little or no effect on the airways of the CD-1 and C3H mouse strains. Vasoactive intestinal peptide potently relaxed the carbachol and precontracted the mouse trachea and bronchi. However, vasopressin, another bioactive peptide, potently and efficaciously contracted the mouse trachea and upper bronchi but had little effect on the lower bronchi. Vasopressin was the most potent and efficacious contractile agonist tested in this study. Contractions were observed with endothelins-1, -2 and -3 on mouse trachea and bronchi, but marked tachyphylaxis was present. Sarafotoxin s6c followed the same pattern suggesting the presence of endothelin ET(B) receptors on the mouse airways. Of all leukotrienes assayed (B(4), C(4), D(4) and E(4)) only leukotriene C(4) weakly contracted the mouse trachea and upper bronchi, but tachyphylaxis was most evident.