当归(Angelica sinesis)及其成分阿魏酸钠对小鼠吞噬功能的影响

当归为中医常用的补血活血药之一。设想当归的补血活血可能和增强机体免疫功能有关,故进行本项研究。实验分两部分:(1)给小鼠静脉注射当归16g/kg或阿魏酸钠100～200mg/kg均能显著地促进单核吞噬细胞系统对刚果红的廓清率。(2)给小鼠灌胃阿魏酸钠0.3g/kg或皮下给0.2g/kg能增强腹腔巨噬细胞吞噬鸡红细胞的能力。皮下给当归20g/kg也有增强作用。     

当归(Angelica sinesis)及其成分阿魏酸钠对小鼠吞噬功能的影响

当归为中医常用的补血活血药之一。设想当归的补血活血可能和增强机体免疫功能有关,故进行本项研究。实验分两部分:(1)给小鼠静脉注射当归16g/kg或阿魏酸钠100～200mg/kg均能显著地促进单核吞噬细胞系统对刚果红的廓清率。(2)给小鼠灌胃阿魏酸钠0.3g/kg或皮下给0.2g/kg能增强腹腔巨噬细胞吞噬鸡红细胞的能力。皮下给当归20g/kg也有增强作用。     

环丙氟哌酸的药效学和毒理学研究

本文研究了环丙氟哌酸的体外抗菌作用、体内保护作用、小鼠和大鼠一次给药的半数致死量和安全试验。结果表明,环丙氟哌酸对革兰氏阴性菌的MIC范围为0.005～0.19μg/ml,抗菌活性强于氟哌酸、氟啶酸和吡哌酸;对革兰氏阳性菌的 MIC为0.045～1.50μg/ml,其抗革兰氏阳性菌活性明显强于上述对照药。小鼠分别感染金葡球菌、大肠杆菌和绿脓杆菌后的半数有效量明显优于氟哌酸、氟啶酸和吡哌酸。小鼠一次给药的半数致死量,口服LD_(50)为2991.52mg/kg; 静脉为223.88mg/kg;肌肉和皮下的LD_(50)分别为831.08mg/kg和1133.42mg/kg. 大鼠口服LD_(50)>5000mg/kg,静脉LD_(50)>200mg/kg;肌肉和皮下分别为>1000mg/kg和>1200mg/kg。狗口服50mg/kg日服三次为期2日和口服100mg/kg日服一次为期7日,未见毒性反应和功能改变,也未见病理组织学变化。     

当归精油对脓毒症小鼠的治疗作用

目的:观察当归精油对脓毒症小鼠的治疗作用。方法:i.v.给予细菌脂多糖复制小鼠脓毒症模型,i.v.给予不同剂量的当归精油,记录小鼠7 d生存率,ELISA法测定血清中细胞因子TNF-α和IL-6含量。结果:在100 mg/kg剂量下,当归精油可提高内毒素(25 mg/kg)攻击小鼠的生存率(P<0.01);在内毒素(25 mg/kg)攻击前、后2 h内给药能提高小鼠生存率,提前1 h预防性给药生存率最高(P<0.01);25～100 mg/kg当归精油能对抗0.125 mg/kg内毒素引起的TNF-α、IL-6水平增高,降低小鼠血清TNF-α、IL-6水平(P<0.05或P<0.01)。结论:当归精油能拮抗内毒素引起的炎症反应,对脓毒症有一定的治疗作用。     

当归及其成分阿魏酸对大鼠血小板聚集和5-HT释放的影响

本文报告当归及其成分阿魏酸对大鼠血小板聚集性和5-HT释放反应的影响。结果表明,当归水剂在试管内当浓度为200～500mg/ml,阿魏酸0.4～0.6mg/ml时抑制ADP和胶原诱导的大鼠血小板聚集。静脉注射当归20g/kg 5分钟后对ADP和胶原诱导的大鼠血小板聚集有明显的抑制作用。阿魏酸钠0.2g/kg和0.1g/kg静脉注射时分别抑制ADP和胶原诱导的大鼠血小板聚集。用³H-5HT标记血小板,观察血小板聚集和释放反应的关系。当归水剂500mg/ml和阿魏酸钠1～2mg/ml对凝血酶诱导的血小板聚集有明显抑制作用,同时也抑制³H-5HT从血小板中释放。     

喜树碱前体多相脂体的药理学研究

本文报道了对喜树碱前体(A-CPT)及喜树碱前体多相脂质体(A-CPT-pl)的药理学研究结果。结果表明,A-CPT腹腔注射给药(ip)及经口腔给药(PO),寇氏法求得小鼠的LD50分别为159.3mg/kg及33.7mg/kg,较喜树碱钠盐(CTP-Na)的毒性降低,按最大允许给药容量(0.5ml/10g)ip或PO A-CPT-pl 50mg/kg,在观察期间未见死亡。抑瘤试验结果表明,A-CPT-pl对S180及HepS的抑制率可达74%及82%,可使荷EAC小鼠的生命延长126%;A-CPT对S180及HepS的抑制率可达52%及53%,可使荷EAc小鼠的生命延长54%。肿瘤相伴免疫试验结果表明,每日ip,A-CPT-pl 0.5mg/kg,连续9天,对小鼠肿瘤相伴免疫没有明显影响。     

度洛西汀的动物急性毒性试验

目的 度洛西汀动物急性毒性的研究.方法 通过管饲法给药观察症状来判断结果.结果 小鼠口服给药的LD50为300～400mg/kg,大鼠口服给药的LDS0为500～600mg/kg(雄性)和300～500mg/kg(雌性).狗最大给药剂量达100mg/kg未见动物死亡.结论 小鼠、大鼠和狗度洛西汀单剂量口服给药后可见与中枢神经系统相关的药理作用,诸如震颤、惊厥、呕吐、散瞳、流涎以及反应增强.     

应用蒙特卡洛模拟法评估伏立康唑临床给药方案

目的:为伏立康唑临床个体化用药提供参考。方法:汇总伏立康唑对烟曲霉和白色念珠菌的最低抑菌浓度(MIC)分布情况,以及伏立康唑在不同人群中的药动学参数,采用水晶球软件11.1.2.4对同一人群不同给药方案和不同人群同一给药方案进行蒙特卡洛模拟(MCS),以达标概率(PTA)和累积反应分数(CFR)为评价指标。结果:当免疫功能低下儿童的给药剂量为4、6 mg/kg时,MIC≤0.125 mg/L即可满足PTA>90%;当给药剂量增加至8 mg/kg时,MIC≤0.25 mg/L才可满足PTA>90%。对于应用相同给药方案(4 mg/kg)的不用人群而言,免疫功能低下青少年的MIC≤0.25 mg/L,健康成年人、造血干细胞移植患者、免疫功能低下成年人的MIC≤0.5 mg/L时,可满足PTA>90%。免疫功能低下儿童不同给药剂量(4、6、8 mg/kg)以及给药剂量同为4 mg/kg的不同人群(免疫功能低下青少年、健康成年人、造血干细胞移植患者、免疫功能低下成年人)对烟曲霉的CFR值分别为42.53%、58.41%、77.74%、70.16%、89.40%、93.72%、95.42%,对白色念珠菌的CFR值分别为96.68%、97.13%、97.94%、97.54%、98.07%、98.28%、98.35%。结论:上述纳入研究的不同人群的各种给药方案均能有效控制白色念珠菌感染,而对于免疫功能低下儿童和青少年则需适当增加给药剂量以满足烟曲霉感染临床治疗的需要。     

隆力奇纯蛇粉免疫作用的初步观察

目的探讨隆力奇纯蛇粉对小鼠免疫功能及对抗免疫抑制剂作用的影响.方法48只小鼠随机分为阴性组(A组)、纯蛇粉8g/kg(B组)环磷酰胺50mg/kg(C组)、纯蛇粉8g/kg+环磷酰胺50mg/kg(D组),其中A、C组给予普通饲料,B、D组给予拌入纯蛇粉的饲料,自由进食30d,在免疫后的第4天,C、D组每只动物背部皮下注射环磷酰胺50mg/kg.测定小鼠脾重,胸腺重,并采用抗体形成细胞(PFC)检测法,血清溶血素测定法、迟发型变态反应(DTH)及α-萘乙酸酯酶(ANAE)染色法对小鼠体液及细胞免疫功能进行测定.结果小鼠喂养30d后处死,称取胸腺.脾脏重量,结果显示纯蛇粉组的脾脏及胸腺重量均高于其他组,并对免疫抑制剂环磷酰胺所致的两者重量减轻有一定的对抗作用.     

绵毛黄芪总甙的免疫活性作用

<正> 绵毛黄芪总甙(As)是新疆塔城地区绵毛黄芪(Astragalus sieversianus Pall)提取物,由中国科学院新疆分院化学所植化室提供。本文探讨了As对CR小鼠的免疫功能的影响。1 对小鼠碳粒廓清作用的影响ICR小鼠随机分5组:溶剂对照组,ig As 50mg/kg、75mg/kg给药组,As75mg/kg加环磷酰胺(Cy)110mg/kg组及scCy组(10mg/kg),给药7d。按常规方法测定并计算廓清指数(K)值。结果给药组分别为26.45+9.46及21.66±8.73,与对照组10.01±3.08比较P<0.01;Cy组为5.01±2.87,与As+Cy组11.89+4.82比较P<0.05。表明As能提高小鼠吞噬能力。2 对小鼠血清溶血素生成的影响ICR小鼠分组及给药方法同上。于给药第3d ip37.5％,SRBC 0.2ml致敏,致敏1h后,小鼠取血测定其半数溶血值(HC_(56)~-).结果As组分别为140.17±44.23及178.18±25.10,与对照组73.34±42.14比较P<0.01)。Cy组30.66±12.63与As+Cy组71.53±29.41比较P<0.01。表明As能促进小鼠抗体生成.     

裂褶菌孢内多糖和孢外多糖对小鼠免疫功能的影响

裂褶菌孢内多糖(SPG₁)和孢外多糖(SPG₂)是分别从发酵培养的裂褶菌菌丝体和发酵液中提取的多糖。SPG₁和SPG₂均能显著促进Con A诱导的小鼠脾淋巴细胞增殖反应,SPG₁还显著地对抗氢可的松对淋巴细胞增殖反应的抑制作用。SPG₁和SPG₂均可恢复14月龄老年小鼠低下的脾淋巴细胞增殖反应。给小鼠ip SPG₁和SPG₂均能显著增强二硝基氯苯(DNCB)所致小鼠迟发型皮肤过敏反应(DCH)。小鼠ip SPG₁可显著增强羊红细胞(SRBC)诱导的小鼠脾脏空斑形成细胞(PFC)反应。SPG₁和SPG₂还可使老年小鼠的PFC反应恢复至成年小鼠水平。     

Evaluation of immunotoxicity induced by diazinon in C57bl/6 mice

Diazinon (DZN), an organophosphate insecticide, has been used in agriculture for several years. It is possible the residue of this compound to be recycled in the biological system. There is no report on DZN immunotoxicity potential. In the present study, we examined the immunotoxic effects of intraperitoneally administered DZN in the C57bl/6 female mice. Diazinon was administered at doses of 25, 2, and 0.2 mg/kg for 28 days (five injections per week). Animals were then sacrificed to observe the cellularity or histopathological changes in thymus, spleen, bone marrow, and peripheral blood. Furthermore, humoral and cellular functional responses such as Hemagglutination titration (HA), IgM-Plaque Forming Colony Assay (PFC), Delayed-Type-Hypersensitivity (DTH) to SRBC, and T cell subtyping (CD4/CD8) were determined. The results showed that DZN at 25 mg/kg not only could produce gross histopathological changes in thymus and spleen but also could suppress both humoral and cellular activity of the immune system. At lower doses (0.2 and 2 mg/kg) there were no observable alteration in cellularity or histology of immune tissues. However, DZN at medium dose (2 mg/kg per day) could inhibit RBC-cholinesterase and showed a mild decrease (P < 0.1) in thymus/body-weight ratio and DTH response. At dose of 0.2 mg/kg no histopathological or functional disturbances were detectable. These results indicate that DZN has immunosuppressive effects in the C57bl/6 mice at doses more than 2 mg/kg. The present results however indicate that under recommended Allowed Daily Intake (ADI) limit (<0.02 mg/kg), no observable immunotoxicity effect is expected.     

Dose-linear pharmacokinetics of oleanolic acid after intravenous and oral administration in rats

The pharmacokinetics of oleanolic acid was evaluated in vitro and in vivo. From Caco-2 cell permeation studies, oleanolic acid was a low permeability compound with no directional effects, suggesting a low in vivo absorption mediated by a passive diffusion. Oleanolic acid was metabolically unstable following incubation with rat liver microsomes in the presence of NADPH. After intravenous injection at doses of 0.5, 1 and 2 mg/kg doses, oleanolic acid showed dose-linear pharmacokinetics as evidenced by unaltered CL (28.6-33.0 ml/min/kg), Vss (437-583 ml/kg), dose-normalized AUC (16.0-17.9 microg min/ml based on 1 mg/kg) and t1/2 (41.9-52.7 min). Following oral administration of oleanolic acid at doses of 10, 25 and 50 mg/kg, Tmax, t1/2, dose-normalized Cmax (66-74 ng/ml based on 25 mg/kg) and dose-normalized AUC (5.4-5.9 microg min/ml based on 25 mg/kg) were comparable between 25 and 50 mg/kg dose, but the plasma concentrations at 10 mg/kg dose were not measurable as they were below the limit of quantitation (2 ng/ml). The absolute oral bioavailability was 0.7% for oral doses of 25 and 50 mg/kg. The extent of urinary excretion was minimal for both i.v. and oral doses. The very low oral bioavailability of oleanolic acid could be due to a poor absorption and extensive metabolic clearance.     

国产环孢素A对小鼠免疫功能的抑制作用

当剂量为25～100mg/kg·d~(-1),ig×4d时,国产环孢素A(CsA)显著抑制小鼠脾脏空斑形成细胞数和溶血素生成,并呈剂量依赖方式。该剂量给药10d,可显著抑制2,4—二硝基氯苯所致小鼠迟发型皮肤超敏反应。CsA(50 mg/kg·d~(-1),ig×14d)能明显延长小鼠移植心脏的存活时间。CsA(50,100mg/kg·d~(-1),ig×4d)对小鼠iv碳粒廓清速率和骨髓细胞数均无明显影响。国产CsA和进口CsA对小鼠脾脏空斑形成细胞反应的抑制作用无显著差异。     

Immunotoxicity of paraquat after subacute exposure to mice

The immunotoxic effect of paraquat (PQ), a herbicide that has been used widely in agriculture was investigated using Balb/c mice. Paraquat was administered at doses of 1, 0.1, and 0.01 mg/kg for 21 days. Body weight, organ weight, cellularity of spleen, delayed type of hypersensitivity (DTH) response, plaque-forming cell (PFC) assay, hemagglutination titer (HA), quantitative hemolysis of SRBC (QHS) assay, spleen cell subtypes, cytokine production and lymphocyte proliferation assay were studied in various groups of animals. Results showed that high dose of PQ (1 mg/kg) could suppress both cellular and humoral activity of the immune system. PQ at medium dose (0.1 mg/kg) did not show any changes in organ weight, body weight and spleen cellularity but significantly decreased the proliferation response to PHA and the production of IFNγ. PQ at low dose (0.01 mg/kg) did not produce any significant changes in humoral or cellular responses of the immune system. In conclusion, paraquat at high dose has an inhibitory effect on the cell-mediated and humoral immunity. It seems that PQ has no adverse effects on mice immune system at low doses of 0.01 mg/kg, which is two times the PQ allowed daily intake (ADI) limit.     

delta1-tetrahydrocannabinol, cannabidiol and cannabinol effects on the immune response of mice.

delta1-tetrahydrocannabinol (THC) elicited a dose-dependent (1, 5, 10 mg/kg) depression of the immune response, of immature mice, stimulated with sheep red blood cells. The impairment of humoral immunity was specific for THC but not for cannabidiol at 25 mg/kg or cannabinol at 25 mg/kg. The mice were given four daily doses (i.p.) of either drug or vehicle (Tween 80-propylene glycol in 1% saline) or a single injection (i.p.) of sheep red blood cells in addition to four daily doses (i.p.) of drug or vehicle. Suppression of the antigenic response by THC was reflected as a reduction of splenic weight, reduction in the number of splenic antibody-forming cells, lowered hemagglutination titer and reduction in the percentage of splenic white pulp of total spleen volume.     

In vivo and in vitro studies on the genotoxicity of cadmium chloride in mice

The genotoxic effect of cadmium chloride was evaluated in chromosomes of experimental mice using in vivo and in vitro studies. In vivo the induction of micronuclei, sister chromatid exchange in mouse bone marrow and chromosomal aberrations in both somatic and germ cells was investigated. Doses 1.9, 5.7 and 7.6 mg kg(-1) body wt. (single i.p. treatment) induced a significant and dose-dependent increase in the percentage of polychromatic erythrocytes with micronuclei. Such a percentage reached 2.1% with the highest tested dose, compared with 0.57% for the control (non-treated) and 2.2% for mitomycin c as the positive control. The dose of 1.9 mg kg(-1) body wt. had no significant effect with respect to sister chromatid exchange (SCE) but the doses of 5.7 and 7.6 mg kg(-1)body wt. increased the frequency of SCEs significantly. The frequency of SCE reached 7.35 +/- 0.26 per cell after treatment with the highest tested dose, which is a less than twofold increase compared with the control frequency of 4.6 +/- 0.42 per cell. However mitomycin c induced a much higher effect (12.1 +/- 0.73). Cadmium chloride also induced a significant increase in the percentage of chromosomal aberrations in mouse bone marrow at the doses of 5.7 and 9.5 mg kg(-1) body wt. (single i.p. treatment). The effect is a function of cadmium chloride concentration. Moreover, cadmium chloride induced its maximum effect concerning the induction of chromosomal aberrations in mouse bone marrow cells 24 h after treatment, compared with 12 and 48 h. In germ cells, chromosomal aberrations were observed in mouse spermatocytes 12 days post-treatment with the dose of 5.7 mg kg(-1) body wt. Moreover, a pronounced reduction in the number of spermatocytes was observed after administration of cadmium chloride (0.9, 1.9 and 5.7 mg kg(-1) body wt.) In in vitro studies, the three tested concentrations of 10, 15 and 20 microgram ml(-1) cadmium chloride induced a statistically significant increase in the frequency of SCEs in cultured mouse spleen cells. The concentrations of 15 and 20 microgram ml(-1) also induced chromosomal aberrations in mouse spleen culture. The ability of vitamin C (l-ascorbic acid) to minimize the incidence of chromosomal aberrations induced by cadmium chloride in cultured mouse spleen cells was investigated. Vitamin C at the concentrations of 3 and 6 microgram ml(-1) significantly minimized the percentage of aberrant cells induced by cadmium chloride.     

Assessment of the immunotoxic potential of the fungicide dinocap in mice.

The immunotoxic potential of dinocap was evaluated in female C57BL/6J mice following in vivo and in vitro exposure to this fungicide. In in vivo studies, groups of mice were dosed by gavage with technical grade dinocap at dosages ranging from 12.5 to 50 mg/kg per day for 7 or 12 days and selected immune functions examined. Mice dosed at 50 mg/kg per day dinocap died after 4 days of dosing. Twelve days of dosing with dinocap at 25 mg/kg per day resulted in decreased thymus weights and cellularity, and increased spleen weights. No changes were observed in body weight, absolute differential peripheral leukocyte counts, the lymphoproliferative responses to B- or T-cell mitogens, the mixed lymphocyte reaction, or natural killer (NK) cell activity of spleen cells from mice exposed to dinocap. Lymphoproliferative responses to concanavalin A (Con A) and phytohemagglutinin (PHA), however, were reduced in thymocytes from mice dosed at 25 mg/kg per day dinocap. The cytotoxic T lymphocyte (CTL) response to P815 mastocytoma cells was enhanced in mice exposed for 7 days to 25 mg/kg per day dinocap. Exposure of mice for 7 days to 25 mg/kg per day dinocap also caused a significant reduction in the IgM and IgG plaque-forming cell (PFC) response to sheep red blood cells (SRBC). A time-course study indicated that dinocap-induced suppression of the IgM PFC response was due to a delay in the peak PFC response to SRBC. In vitro studies using murine thymocytes cultured with dinocap (10 micrograms/ml for 72 h) resulted in suppression of the proliferative response to Con A and PHA. Exposure of thymocytes to dinocap in vitro for as little as 30 min resulted in suppression of the mitogen-stimulated response in the absence of any apparent direct cytotoxic effect. These results suggest that dinocap alters the immune system of the mouse, however, these effects are relatively modest in terms of adverse immune function and are only seen at relatively high exposure levels.     

左旋18-甲基炔诺酮肟与左旋18-甲基炔诺酮的抗生育作用比较

本文比较了LNGO和LNG对大鼠的抗生育作用,结果表明,LNGO在剂量为10mg/kg·d时可以完全抑制大鼠着床,剂量为40,60mg/kg·d时有明显抗早孕作用。光电镜观察提示,剂量为10mg/kg·d时,对大鼠子宫内膜间质细胞和上皮细胞均有影响。组织培养研究发现,对体外人胎盘滋养层细胞有直接损伤作用。LNG对大鼠未见抗着床及抗早孕作用,对大鼠子宫内膜和体外人胎盘滋养层细胞也均未见明显作用。     

Immunomodulation and antitumor activity by a polysaccharide-protein complex from Lycium barbarum

The modulation of a polysaccharide-protein complex from Lycium barbarum (LBP3p) on the immune system in S180-bearing mice was investigated. The mice inoculated with S180 cell suspension were treated p.o. with LBP3p (5, 10 and 20 mg/kg) for 10 days. The effects of LBP3p on transplantable tumors and macrophage phagocytosis, quantitative hemolysis of sheep red blood cells (QHS), lymphocyte proliferation, the activity of cytotoxic T lymphocyte (CTL), interleukin-2 (IL-2) gene expression and lipid peroxidation were studied. LBP3p could significantly inhibit the growth of transplantable sarcoma S180 and increase macrophage phagocytosis, the form of antibody secreted by spleen cells, spleen lymphocyte proliferation, CTL activity, IL-2 mRNA expression level and reduce the lipid peroxidation in S180-bearing mice. The effect is not dose-dependent in a linear fashion. A total of 10 mg/kg dose is more effective than 5 and 20 mg/kg doses. This suggests that LBP3p at 10 mg/kg has a highly significant effect on tumor weight and improves the immune system.