水解南珠片对免疫低下小鼠免疫功能的影响

本实验以腹腔注射环磷酰胺建立免疫低下小鼠模型,灌胃给予水解南珠片高、中和低剂量(2.04 g/kg,1.02 g/kg和0.51 g/kg)30 d,观察水解南珠片对免疫低下小鼠免疫功能的影响。结果显示,水解南珠片高剂量(2.04 g/kg)能显著提高免疫低下小鼠单核巨噬细胞系统碳粒廓清指数K(p0.05);水解南珠片高、中、低剂量(2.04 g/kg,1.02 g/kg,0.51 g/kg)能显著提高免疫低下小鼠外周血T淋巴细胞相对数量(p0.01);水解南珠片高、中剂量(2.04 g/kg,1.02 g/kg)能显著提高免疫低下小鼠血清溶血素吸光度值(p0.01)。上述结果表明,水解南珠片对免疫功能低下小鼠的固有免疫、细胞免疫和体液免疫功能均有一定的增强作用。     

蜜环菌饮料对机体活性的调节作用研究

为了研究蜜环菌饮料对小鼠机体功能的影响,采用环磷酰胺(CY)造模法制作小鼠免疫抑制模型,通过灌胃不同剂量蜜环菌饮料,研究对小鼠机体免疫功能的影响,同时通过测定实验小鼠肠道中细菌总数、大肠杆菌数、乳酸菌和双歧杆菌数等,分析不同剂量的蜜环菌饮料对肠道菌相的影响,最后对小鼠进行了急性毒性试验研究,以检测饮料有无毒副作用。结果表明蜜环菌饮料可明显提高小鼠脾脏和胸腺指数,促进脾脏及胸腺的发育,促进巨噬细胞的吞噬活性,明显增强小鼠的免疫功能,同时还能促进小鼠肠道有益菌的生长,改善肠道微生物区系环境,饮料没有对小鼠产生任何的毒副作用。证明蜜环菌饮料不仅增强机体免疫功能,同时还增强肠道功能,保持和促进机体健康。     

N-CWS灌胃对小鼠移植性肿瘤及免疫功能的影响

为了考察红色诺卡氏菌细胞壁骨架(Nocardia rubra cell wall skeleton,N-CWS)灌胃给药对小鼠的体内抑瘤效应及其免疫调节作用,采用小鼠肉瘤S_(180)的移植性肿瘤模型,检测N-CWS灌胃给药的抑瘤活性;同时观察N-CWS体内细胞毒作用和对正常小鼠的毒性、免疫器官重量、巨噬细胞(MΦ)吞噬功能及脾淋巴细胞转化的影响.结果显示,小鼠灌服N-CWS的LD_(50)＞1.2 g/kg;N-CWS 200、400、800 mg/kg剂量灌胃小鼠对S_(180)有明显的抑制作用,其抑瘤率分别为63.33%、71.11%、64.88%;与对照组比较,N-CWS可增加免疫器官重量和提升外周血白细胞数量、能明显提高小鼠MΦ的吞噬活性及显著提高淋巴细胞转化率(P＜0.05),同时N-CWS激活了的MΦ对肿瘤细胞的细胞毒效应亦明显增强(P＜0.05).因此N-CWS适用于口服给药,对小鼠移植性肿瘤有明显的抑制作用,其抗肿瘤作用可能与增强机体免疫功能有关.     

纯大鲵粉对小鼠抗疲劳作用及免疫功能的影响

目的 考察纯大鲵粉对小鼠免疫功能的影响和抗疲劳作用.方法 纯大鲵粉小鼠灌胃,检测免疫器官指数、血清溶血素含量、脾抗体细胞生产数、碳粒廓清指数、耳肿胀度,研究对小鼠免疫功能的影响.测定小鼠负重游泳时间,检测血乳酸、血清尿素氮及肝糖原含量,研究其抗疲劳作用.结果 纯大鲵粉能增加小鼠免疫功能,延长小鼠游泳时间,降低血乳酸变化幅度,提高肝糖元储备,降低尿素氮含量.结论 纯大鲵粉具增强小鼠免疫功能和抗疲劳作用.     

牦牛骨胶对小鼠应激及免疫机能的功能影响

目的：通过实验研究牦牛骨胶对小鼠应激及免疫功能的影响。方法：采用昆明小鼠为实验对象,观察小鼠负重游泳、耐缺氧、高温和低温存活时间,以及正常小鼠网状内皮系统吞噬能力和溶血素抗体水平。结果：灌胃牦牛骨胶能明显增强小鼠耐缺氧、耐寒、抗疲劳的能力,也能增强小鼠网状内皮系统吞噬功能、明显升高免疫受抑小鼠的HC50,具有显著的抗应激和增强免疫功能的作用。     

香菇多糖对微生态失调小鼠肠道菌群及免疫功能的调节作用

目的 探讨香菇多糖对微生态失调小鼠肠道菌群及免疫功能的调节作用.方法 经盐酸林可霉素灌胃建立肠道微生态失调小鼠模型,香菇多糖灌胃治疗,同时设正常对照组、自然恢复组和丽珠肠乐组.7d后处死各组小鼠,进行肠道菌群定量、免疫器官体重及其淋巴细胞转化率检测.结果 用香菇多糖对肠道微生态失调小鼠进行治疗后,小鼠肠道双歧杆菌、乳酸杆菌数量显著增加,而肠杆菌和肠球菌的数量显著降低;脾脏指数明显增加,对胸腺指数无影响;显著增强了淋巴细胞转化率.结论 盐酸林克霉素灌胃能诱导微生态失调小鼠模型的有效建立.香菇多糖能调整小鼠肠道菌群及免疫功能.     

豆腐柴根提取物对小鼠非特异性免疫功能的影响

将不同剂量豆腐柴(Premna Microphylla Turcz)根提取物分别灌胃给药,通过小鼠刚果红吞噬试验,初步研究了豆腐柴根提取物对小鼠非特异性免疫功能的影响。结果表明,豆腐柴根提取物具有增强机体非特异性免疫功能的作用,其中以C组的效果最为显著。该研究为合理开发利用豆腐柴这一野生药物资源提供了科学的实验依据。     

红色诺卡氏菌的生物活性

为了考察红色诺卡氏菌菌体(NC)的生物活性, 通过一定浓度的NC对小鼠灌胃给药, 检测其毒性及对免疫器官、巨噬细胞(MΦ)吞噬功能的影响和对肉瘤S180抑制作用。结果表明小鼠口服NC, LD50>10 g/kg; NC明显增加小鼠胸腺脾脏重量、提升白细胞数量和提高小鼠MΦ的吞噬活性; 对小鼠腹腔MΦ具有明显的激活作用, 激活了的MΦ能增强抑杀白色念珠菌作用, 正常的小鼠MΦ也有一定的杀菌作用, 两者差异显著; 对小鼠S180腹水型转实体瘤具有明显的抑制作用。由此得出的结论是, NC毒性低, 能显著增强机体     

壳聚糖载黄芪多糖纳米粒调节糖尿病小鼠免疫功能

研究低分散度壳聚糖载黄芪多糖纳米粒(LCA)对糖尿病(DM)小鼠免疫功能的影响。注射链脲佐菌素与环磷酰胺混合试剂建立DM合并免疫力低下小鼠模型,酶法制备低分散度壳聚糖,离子交联法制备低分散度壳聚糖纳米粒,超声包埋黄芪多糖制备药物对昆明小鼠灌胃,每天1次,连续30 d。ELISA法检测小鼠血清Ig M、Ig G与INF-γ的含量,碳粒廓清法测定非特异性免疫功能,耳肿胀法检测迟发型变态反应,MTT法检测脾淋巴细胞增殖率以反映细胞免疫功能。结果显示灌胃350 mg/(kg·d)LCA显著提高血清Ig M、Ig G的分泌,显著降低INF-γ表达量,增强碳粒廓清率,提高小鼠迟发型变态反应(DTH),改善脾淋巴细胞增殖反应。适当剂量的低分散度壳聚糖载黄芪多糖纳米粒能提高DM小鼠体液免疫、非特异性免疫及细胞免疫功能,且效果优于纯黄芪多糖。     

卡介苗溶菌黏膜免疫调理剂对激活荷瘤小鼠免疫功能的研究

观察卡介苗溶菌黏膜免疫调理剂对荷瘤小鼠免疫功能的激活。将SPF小鼠分组后用黑色素瘤B16和肝癌实体瘤H22感染,随后以灌胃途径引入本调理剂,分别发现它能促进荷瘤小鼠血清溶菌酶含量上升和T细胞介导的迟发型变态反应增强。试验结果表明,卡介苗溶菌黏膜免疫调理剂对荷瘤小鼠有升高其血清溶菌酶含量和增强迟发型变态反应的作用。     

Separation of mitogen-induced suppressor and helper cell activities during inhibition of interferon production by cyclic AMP.

The effect of exogenous cyclic AMP on mitogen-induced suppression and enhancement of the in vitro plaque-forming cell (PFC) response and on mitogen induction of immune interferon (also called type II) in cultures was examined. Mitogen induction of immune interferon was quantitatively associated with mitogen-induced suppressor activity, and cyclic AMP blocked both the suppressor activity and the production of immune interferon in mouse (C57B1/6) spleen cell cultures. The evidence is as follows: (a) The concentrations of dibutyryl cyclic AMP that blocked T-cell mitogen (staphylococcal enterotoxin A) suppressor activity were the same as those that blocked mitogen induction of immune interferon. (b) The blocking action of dibutyryl cAMP on both the suppressor and interferon effects of mitogen was a function of the time of dibutyryl cAMP addition to cultures relative to mitogen addition. (c) A dramatic immunoenhancing effect of mitogen occurred in the presence of dibutyryl cAMP under conditions that blocked production of immune interferon. Specifically, mitogen-induced helper cell function is dramatically enhanced in the presence of dibutyryl cyclic AMP, if the mitogen is added to cultures 24 to 48 hr after SRBC and dibutyryl cyclic AMP. Dibutyryl cyclic GMP did not affect the mitogen- or cyclic AMP-induced effects under the conditions of our test system. Under the conditions described here, then, cyclic AMP appears to selectively block suppressor cell activity while allowing or aiding mitogen-induced helper cell activity. It is possible that the immune response is a reflection of the ratio of helper to suppressor activities in the system.     

Changes in the cAMP level in macrophages during the phagocytosis of Salmonella typhimurium. II. Effect of the virulence of microorganisms and the immune status of the macrophages on the dynamics of changes in cAMP levels

The dynamics of changes in the level of intracellular cyclic AMP in nonimmune and immune macrophages in the process of the phagocytosis of S. typhimurium virulent strain, its heated variant and its mutant with low virulence was studied. A transient increase in the level of cyclic AMP was shown to occur during the first 30 minutes of phagocytosis; this increase did not depend on the kind of the phagocytized object and on the activity of macrophages and neither had it any influence on the outcome of phagocytosis. The virulent strain also induced the three-fold increase of the level of cyclic AMP in nonimmune macrophages prior to their disintegration caused by the cytopathogenic action of the microorganism. In immune macrophages the virulent strain did not induce the secondary increase of the level of cyclic AMP.     

Effect of dietary ascorbic acid on growth and non-specific immune responses of tiger puffer, Takifugu rubripes

We report nutritional physiology and non-specific immune responses of ascorbic acid (AA) in puffer fish for the first time. This study aimed to examine the essentiality and requirements of AA in diets for the tiger puffer, Takifugu rubripes based on growth performance, liver AA and bone collagen concentration, and non-specific immune responses. Five casein-gelatin based semi-purified diets were formulated to contain five graded levels of l-ascorbyl-2-monophosphate at 0, 40, 80, 160 and 700mg/kg (designated as AMP0, AMP40, AMP80, AMP160 and AMP700, respectively) and fed to triplicate groups of fish. After 10weeks of feeding trial, growth performances of fish (initial body weight, 35g) fed the AMP0 were significantly lower compared to that of fish fed diets supplemented with AMP. The fish fed the AMP0 diet also exhibited significantly lower hematocrit, condition factor and hepatosomatic index compared to the fish fed diets supplemented with AMP. Phagocytic activity (NBT assay) was significantly lower in fish fed the AMP0 diet than in fish fed the AMP containing diets. Plasma lysozyme activity of fish fed the AMP80 and AMP160 was significantly higher than that of fish fed the AMP0. Dietary supplementation of AMP significantly increased the liver superoxide dismutase in the fish. Myeloperoxidase activity of fish fed the AMP0 was significantly lower compared to that of fish fed the AMP containing diets. Bone collagen level tended to increase numerically and total AA concentration in liver of fish was significantly increased in a dose dependent manner by the supplementation of AMP. Therefore, tiger puffer requires exogenous ascorbic acid and the optimum dietary level could be 29mg AA/kg diet for normal growth and physiology. Dietary AA concentration over 82mg/kg could be required to enhance non-specific immune responses of the fish. However, it does not seem that the fish needs an overdose of dietary AA (>160mg/kg) for better non-specific immune responses.     

Dexamethasone increases intracellular cyclic AMP concentration in murine T lymphocyte cell lines

The effects of the synthetic glucocorticoid dexamethasone on the cAMP content of murine T lymphocyte cell lines has been investigated. Incubation of the 3B4.15 T cell hybrids with dexamethasone results in an average 5-fold increase in intracellular cyclic AMP levels after 6 h of treatment. This phenomenon is abolished in the presence of RU486 and of cycloheximide, indicating that it requires binding of the drug to the intracellular glucocorticoids receptor and de novo protein synthesis. Dexamethasone-induced elevation of intracellular cyclic AMP correlates with both an increase in adenylate cyclase activity and a decrease in phosphodiesterase activity in T cell hybrids. This modulation of cyclic AMP metabolism is independent of serum-derived factors, suggesting that it is not secondary to transmembrane receptor stimulation by an extracellular ligand. We propose that glucocorticoids interfere with the homeostatic control of intracellular cAMP concentration, leading to a sustained increase in the content of this important second messenger in murine T lymphocyte cell lines. This study suggests that elevation of cAMP levels may represent one way by which glucocorticoids modulate the immune response.     

Regulation of CD40L expression by cyclic AMP: contrasting proinflammatory and inhibitory actions

CD40L expression is well recognized to be of critical importance in initiation of the immune response. Because cAMP mediates actions of bronchodilators commonly used in asthma, the effects of cAMP in regulating the immune response are of major importance. Cyclic AMP was found to either inhibit or markedly increase CD40L expression dependent upon the mechanisms of T cell activation. Cyclic AMP inhibited CD40L expression induced by TCR activation. In contrast, cAMP enhanced CD40L induced by CD2-mediated T cell activation or by calcium-dependent mechanisms. While neither CD28 costimulation nor exogenous IL-2 or IL-4 prevented cAMP inhibition in TCR activated cells, addition of calcium ionophore to TCR activation prevented any inhibitory effects and caused cAMP to increase CD40L expression. Actions of cAMP to increase CD40L expression appeared independent of PKC and were not a reflection of generalized cellular activation since neither CD25 nor CD69 expression was affected. The markedly contrasting actions of cAMP to decrease or increase CD40L expression, an important control point in the immune response, could be relevant to actions of commonly used medications including bronchodilators.     

Short term and long term effects of beta-adrenergic effectors and cyclic AMP on nitrendipine-sensitive voltage-dependent Ca2+ channels of skeletal muscle

The effects of short term stimulation of beta-adrenergic receptors and elevations in intracellular cyclic AMP on nitrendipine-sensitive voltage-dependent Ca2+ channels of skeletal muscle cells in vitro has been studied using both the 45Ca2+ flux technique and [3H] nitrendipine-binding experiments. Isoproterenol increased the nitrendipine-sensitive 45Ca2+ influx under depolarizing conditions. The effects of isoproterenol were additive to those of depolarization and were antagonized by alprenolol. Half-maximal inhibition of 45Ca2+ influx induced both by depolarization and by isoproterenol occurred at a nitrendipine concentration of 1 nM. Treatments that resulted in an increased level of intracellular cyclic AMP, such as treatment with 1-methyl-3-isobutylxanthine, theophylline, dibutyryl cyclic AMP, or 8-bromocyclic AMP also resulted in an increased rate of 45Ca2+ entry via nitrendipine-sensitive Ca2+ channel. In contrast, long term treatment of myotubes in culture with isoproterenol and other compounds that increased intracellular cyclic AMP led to a large increase in the number of nitrendipine receptors. This increase was accompanied by a 4-10-fold decrease in the affinity of the receptors for nitrendipine. Alprenolol inhibited the long term effects of isoproterenol. In vivo treatment of 7-day-old chicks with reserpine and alprenolol produced a decrease in the number of skeletal muscle nitrendipine receptors. This decrease in receptor number was accompanied by an increase in the affinity of nitrendipine for its receptor by a factor of 4 to 5. These effects on the nitrendipine receptor were prevented by simultaneous injection of isoproterenol. The results are discussed in relation to the role of beta-adrenergic receptors and intracellular cyclic AMP in the regulation of skeletal muscle Ca2+ channels.     

D-galactose accumulation in rabbit ileum. Effects of theophylline on serosal permeability.

The effects of theophylline and dibutyryl cyclic AMP, on in vitro unidirectional galactose fluxes across the mucosal and serosal borders of rabbit ileum have been studied. 1. When Ringer [galactose] = 2mM, theophylline and dibutyryl cyclic AMP reduce both mucosal-serosal and serosal-mucosal galactose flux by approx. 50%. The K1 for theophylline inhibition of flux in both directions is 2 mM. 1 mM dibutyryl cyclic AMP elicits a maximal inhibitory response. Concurrent with the inhibition in transmural galactose fluxes, theophylline and dibutyryl cyclic AMP increase the tissue accumulation of [galactose] and the specific-activity ratio R of 3H : 14C-labelled galactose coming from the mucosal and serosal solutions respectively. It is deduced that theophylline and dibutyryl cyclic AMP are without effect on the mucosal unidirectional permeability to galactose but cause a symmetrical reduction in serosal entry and exit permeability. 2. Reduction in the asymmetry of the mucosal border to galactose by reducing Ringer [Na], raising Ringer [galctose] or adding ouabain reduces the theophylline-dependent increase in galactose accumulation. 3. Hypertonicity in the serosal solution increases the permeability of the serosal border to galactose and reduces tissue galactose accumulation. Serosal hypertonicity partially reverses the theophylline-depedent effects on galactose transport. Replacing Ringer chloride by sulphate abolishes the theophylline-dependent effects on galactose transport. 4. It is considered that the theophylline-dependent increase in galactose accumulation results from the reduction in serosal permeability. This is shown to be a quantitatively consistent inference. 5. Further support for the view that the asymmetric transport of galactose in rabbit ileum results from convective-diffusion is presented.     

Effects of adenosine 3'':5''-cyclic monophosphate and serum on synthesis of hyaluronic acid in confluent rat fibroblasts.

A small amount of hyaluronic acid is synthesized in confluent cultures of rat fibroblasts, which have a high content of cyclic AMP. Addition of calf serum caused a rapid decrease in the cellular cyclic AMP content and large increases in hyaluronic acid synthetase activity and hyaluronic acid production. Addition of cyclic AMP also caused a marked increase in hyaluronic acid synthetase activity within 2h and then increased hyaluronic acid production. The effects of cyclic AMP and serum on hyaluronic acid synthesis were additive. Prostaglandin E2, which increased the cyclic AMP by stimulating adenylate cyclase, was as effective as cyclic AMP in increasing hyaluronic acid synthetase activity, but AMP was far less effective than cyclic AMP. These results indicate that cyclic AMP itself stimulates the mucopolysaccharide synthesis and that the effect of serum is not due to a decrease in cyclic AMP in the cells.     

Inhibitory mechanism of cis-polyunsaturated fatty acids on platelet aggregation: the relation with their effects on Ca2+ mobilization, cyclic AMP levels and membrane fluidity

The in vitro inhibitory effects of cis-polyunsaturated fatty acids, linolenic (18:2 delta 9,12), alpha-linoleic (18:3 delta 9,12,15) and eicosatrienoic (20:3 delta 11,14,17) acid, on bovine platelet aggregation and their inhibitory mechanism were investigated. These fatty acids inhibited platelet aggregation induced by ADP and thrombin to similar extent. Fluorescence analyses with fura-2-loaded platelets showed that, in the concentration ranges that inhibited aggregation, they also inhibited agonist-induced increase in cytoplasmic Ca2+. According to radioimmunoassay study, addition of these fatty acids increased cyclic AMP contents in the presence of theophylline corresponded with their inhibitory effects on aggregation. These fatty acids induced a 1.6-1.8-fold increase over basal concentration of cyclic AMP in the concentration ranges that fully inhibited aggregation. On the other hand, saturated fatty acid, stearic acid, affected neither aggregation nor cyclic AMP levels. As reported previously [1985) Biochim. Biophys. Acta 818, 391), these unsaturated fatty acids induced increase in membrane fluidity in the same concentration range. These results suggest that inhibition of platelet aggregation by cis-polyunsaturated fatty acids is due to the increase in cyclic AMP levels. This increase seems to be due to stimulation of adenylate cyclase which is mediated by membrane perturbation.     

Cysteine Sulfinic Acid in the Central Nervous System: Antagonistic Effect of Taurine on Cysteine Sulfinic Acid-Stimulated Formation of Cyclic AMP in Guinea Pig Hippocampal Slices

The stimulatory effect of cysteine sulfinic acid on cyclic AMP formation was examined in slices from three different regions of guinea pig brain. The inhibitory effect of taurine on the stimulated formation of cyclic AMP was also studied. Cysteine sulfinic acid (1--10 mM) greatly increased the cyclic AMP level in striatal, cortical, and especially hippocampal slices. In hippocampal slices, taurine (0.1--30 mM) markedly lowered the increase of cyclic AMP induced by cysteine sulfinic acid, but not that induced by glutamate or aspartate. In this region, taurine also reduced the stimulatory effects on cyclic AMP formation of adenosine, norepinephrine, and histamine, but not of depolarizing agents. It did not, however, inhibit the effects of any of these stimulants in cortical slices. These results suggest that sulfur-containing amino acids, such as cysteine sulfinic acid and taurine, regulate the cyclic AMP level in the hippocampus.