白芍总甙对免疫系统的影响

白芍总甙(TGP)对羊红细胞免疫的小鼠脾淋巴细胞体外诱生溶血素(IgM)抗体和刀豆素A诱导小鼠脾淋巴细胞体外增殖反应均呈现低浓度(<0.4μg/ml)促进和高浓度(>0.4μg/ml)抑制的双向调节作用。TGP(5mg/kg,ip)可明显促进辐照加输注受训胸腺细胞体内诱导抗原特异性Th细胞。以上结果提示,TGP对免疫系统的影响有明显的浓度与机能依赖性特征。     

脱氧雪腐镰刀菌烯醇对小鼠胸腺细胞凋亡和增殖的影响

目的:探讨脱氧雪腐镰刀菌烯醇(DON)对小鼠胸腺细胞凋亡和增殖的影响。方法:以动物实验、形态学观察、DNA琼脂糖凝胶电泳、流式细胞术方法研究了不同剂量DON对小鼠胸腺细胞凋亡和增殖的影响及其量效关系。结果:FCM检测结果表明,不同浓度DON均能诱导并促进体内小鼠胸腺细胞凋亡,DON0.5mg/kg、1mg/kg、2mg/kg、4mg/kg、8mg/kg组胸腺细胞的平均凋亡百分率分别为6.35%±1.30%、8.30%±1.33%、8.89%±2.15%、10.70%±0.62%和12.54%±2.08%,在0.5mg/kg到8mg/kg的浓度范围内,随DON浓度的增高,胸腺细胞的凋亡率也相应增高,两者呈显著正相关(r=0.788,P＜0.01)。DNA琼脂糖凝胶电泳结果显示,大剂量(8mg/kg和4mg/kg)DON处理组小鼠胸腺细胞出现了凋亡特有的梯状条带。超微结构观察可见DON处理组小鼠胸腺部分细胞出现核染色质固缩凝聚、胞芽等细胞凋亡的超微结构特征表现。大剂量(8mg/kg和4mg/kg)DON可明显降低小鼠胸腺细胞增殖活性(用PI表示,P＜0.01)。结论:脱氧雪腐镰刀菌烯醇可剂量依赖地诱导并促进小鼠胸腺细胞的凋亡和抑制其增殖。     

当归多糖体外免疫调节作用的实验研究

当归多糖（ＡＳＰ）单独对小鼠脾淋巴细胞有明显促进增殖作用，促进增殖刺激指数最大为１７．５０，并且与ＣｏｎＡ、ＬＰＳ有协同促进小鼠脾淋巴细胞增殖作用当归多糖单独对小鼠胸腺细胞无促进增殖作用，但对由亚适剂量ＣｏｎＡ活化的小鼠胸腺细胞有明显促进增殖作用。此外，当归多糖体外可对抗氢化可的松对小鼠胸腺细胞增殖抑制作用。     

老龄小鼠性腺摘除后胸腺的形态学变化

本文观察了15月龄雌雄ICR小鼠于性腺摘除后第25天胸腺的变化。与对照组相比,胸腺增大,重量增加,皮质增厚且皮髓质分界明显,细胞密度显著增大;皮质/髓质立体计量数值、细胞总数、胸腺细胞数/mm~2及ANAE阳性细胞、非淋巴细胞(NLC)、巨噬细胞(Mφ)一胸腺细胞花环的百分率均增高;电镜下胸腺细胞与明型上皮性网状细胞或Mφ形成的花环更多见。外周血ANAE阳性淋巴细胞明显增多。以上结果表明,老龄小鼠于性腺摘除后,胸腺呈现明显的形态学逆转变化。     

大鼠胚胎胸腺和后肾原基联合异种移植与诱导免疫耐受的初步研究

目的 将大鼠胚胎胸腺与后肾原基联合移植至无胸腺裸小鼠,探讨联合移植能否重建受体细胞免疫功能并诱导受者对异种供者器官的特异性免疫耐受的关系.方法 从受孕第15天(E15)的Lewis大鼠胚胎中提取胸腺、后肾原基,分别植入BALB/c裸小鼠腹腔右肾包膜下及大网膜内.移植后第10周,行胸腺、后肾移植物的形态学检查及移植后肾的功能检测;并进行外周血T淋巴细胞流式细胞学检测、单向混合淋巴细胞反应(MLR)及皮肤移植试验.结果 移植后第10周,移植胸腺及后肾形态发育良好.移植后肾显示一定的排泄功能,联合移植受体双肾切除后的生存时间明显延长(P＜0.05).联合移植受体的外周血T淋巴细胞重建良好;其淋巴细胞对胸腺供体来源的Lewis大鼠脾细胞的刺激呈特异性低反应(P＜0.01);且胸腺供体来源的大鼠移植皮片平均存活时间明显大于C57BL/6小鼠、BN大鼠移植皮片存活时间(P＜0.01).结论 E15 Lewis大鼠胚胎胸腺、后肾原基联合移植至细胞免疫缺陷的裸小鼠,移植物可生长分化形成器官并发挥功能,受体裸小鼠能重建免疫功能,并有可能诱导对同源供体器官的特异性异种移植免疫耐受.     

苯二氮类药物对细胞免疫功能的影响

苯二氮类药物（安定）能促进小鼠胸腺细胞增殖,这种作用以安定5mg/kg腹腔注射,每天一次连续给药5d的作用最强。安定对小鼠脾脏细胞增殖、自然杀伤（NK）细胞毒活性、脾细胞初次抗体产生以及对体外培养胸腺细胞增殖等均无明显影响。安定对截肢应激所致小鼠胸腺、脾脏细胞免疫抑制有拮抗作用,并可有效地拮抗应激导致的小鼠胸腺重量减轻。     

重组白细胞介素2促进小鼠胸腺细胞发育及辐射损伤小鼠免疫功能的恢复

经亚致死量照射的BALB/c小鼠胸腺内残留的胸腺干细胞经历与胚胎胸腺发育十分相似的过程,体内给予IL-2(6×10~5u/kg)可明显促进胸腺细胞由CD4~-CD8~-向CD4~+CD8~+再向CD4~+CD8~-/CD4~-CD8~-分化并明显促进胸腺细胞增殖和亚致死量照射小鼠脾细胞对ConA、LPS 的增殖能力,促进同种异型细胞的混合淋巴细胞反应(MLR)和绵羊红细胞(SRBC)的抗体形成细胞数(PFC)等多项免疫功能的恢复。     

老龄小鼠胸腺内皮细胞的变化

目的研究老化引起胸腺萎缩和功能减低的相关机制。方法用组织化学和免疫荧光染色方法分析胸腺皮质和髓质结构;用BrdU标记流式细胞仪方法研究胸腺内皮细胞增殖;细胞凋亡测定用TUNNEL流式细胞仪方法。结果老龄小鼠胸腺内皮细胞增殖阳性率6.7%,对照年轻小鼠为9.2%。老龄小鼠胸腺内皮细胞凋亡率为11.3%,对照年轻小鼠为2.6%。老龄小鼠胸腺结构出现退行性改变。结论老化引起胸腺内皮细胞增殖能力下降、凋亡率增加和胸腺结构出现退行性改变,可能是老年胸腺萎缩免疫力降低的原因之一。     

淫羊藿苷(ICA)对化疗后免疫抑制小鼠的免疫促进作用

目的:通过观察淫羊藿苷(ICA)对化疗药环磷酰胺(Cy)所致免疫抑制小鼠免疫功能的影响,探讨ICA促进免疫功能的作用及机理.方法:除正常组小鼠外,所有小鼠经腹腔注射Cy(300 mg/kg);第二天开始给予实验组小鼠灌胃不同剂量的ICA[150、80、40 mg/(kg·d)],阳性对照组小鼠尾静脉注射参芪扶正注射液(1 ml/d),模型组给予等量生理盐水,连续干预10天.所有小鼠均于末次给药12小时后处死,计算胸腺指数(TI)和脾指数(SI),光镜下计数外周血和脾淋巴细胞数量.MTT法检测小鼠脾淋巴细胞增殖反应.ELISA法检测TNF-α的含量.乳酸脱氢酶实验(LDH)检测小鼠脾脏NK和CTL细胞的活性.流式细胞术(FACS)检测脾淋巴细胞中NKT和CD3+T细胞的比例.结果:模型组小鼠以上各项免疫指标均有所下降.ICA处理组小鼠脾脏指数和胸腺指数均升高(P<0.01),脾淋巴细胞数量显著增加(P<0.01),但未达到正常对照组水平;ICA明显提高小鼠脾淋巴细胞的增殖反应,促进了小鼠脾NK和CTL细胞对肿瘤细胞的杀伤活性(P<0.01),提高了小鼠脾细胞TNF-α的产生(P<0.01).ICA处理组小鼠脾细胞中CD3+T、NKT细胞比例明显增加(P<0.01).结论:ICA能促进小鼠免疫功能,具有逆转化疗后小鼠免疫抑制状态的作用.     

银杏叶提取物增强大鼠脾脏和胸腺的免疫功能

目的研究银杏叶提取物(GBE)对大鼠脾脏和胸腺免疫功能的影响。方法给SD大鼠灌胃给予(40、120、360)mg/(kg·d)GBE,同时设置对照组。28 d后,水合氯醛麻醉处死大鼠,测量胸腺和脾脏的质量指数;MTT法检测伴刀豆球蛋白A(Con A)诱导的大鼠脾淋巴细胞增殖转化;中性红实验测定大鼠腹腔巨噬细胞吞噬功能;扫描电镜观察大鼠脾脏和胸腺的超微结构变化。结果不同剂量的GBE均可提高胸腺和脾脏的器官质量指数,不同剂量组之间无显著性差异;不同剂量的GBE均可增强大鼠腹腔内巨噬细胞的吞噬作用及各级淋巴细胞的增殖能力,且呈现一定的剂量依赖性。电镜观察发现不同剂量的GBE处理组,大鼠脾脏和胸腺中成熟淋巴细胞数均较对照组增多。结论银杏叶提取物可增强大鼠胸腺和脾脏的免疫功能。     

Dopexamine and cellular immune functions during systemic inflammation

An immune-neuroendocrine interaction that is mediated via β₂-adrenergic receptors has been demonstrated previously. Dopexamine is a substance with strong β₂-adrenergic effects and is used in the treatment of critically ill patients. We therefore investigated the effect of dopexamine infusion on survival and cellular immune functions during systemic inflammation. Sepsis (CLP) was induced in male NMRI mice that received either 0.9% saline, dopexamine (0.05 mg/kg/hour ip, DPX), the selective β₂-adrenergic antagonist ICI 118.551 (0.5 mg/kg ip every 12 hours, ICI) or a combination of both drugs. 48 hours after onset of sepsis, survival rate, splenocyte apoptosis, splenocyte proliferation, splenocyte IL-2, IL-6 and IFN-γ release, and leukocyte distribution were monitored.Dopexamine increased splenocyte apoptosis and normalized the distribution of circulating lymphocytes but did not affect sepsis-induced mortality. ICI 118.551 induced a dramatic increase of mortality paralleled by a decreased splenocyte proliferation and the strongest increase in splenocyte apoptosis. Co-administration of dopexamine abolished the ICI 118.551-induced alterations but this effect seemed to be mediated via a pathway other than adrenergic β₂-receptors.We conclude that dopexamine modulates cellular immune functions during systemic inflammation and that different receptor systems are involved in the mediation of this process. Furthermore, the immunomodulatory effect of β₂-adrenergic blockade was demonstrated.     

Low-level dietary deoxynivalenol and acute exercise stress result in immunotoxicity in BALB/c mice

We hypothesized that acute exercise stress would exacerbate immunosuppressive effects of sub-acute exposure to dietary deoxynivalenol (DON). Male BALB/c mice were fed 0 or 2 mg DON/kg diet for 14 days, 12 animals per dose, and then exercised to fatigue on a treadmill. Mice were euthanized by decapitation, trunk blood and spleens were collected. Single-cell suspensions of splenocytes were used to quantify immune function by plaque hemolysis and conconavalin-A (ConA) stimulated lymphocyte proliferation assays. Serum corticosterone level was determined by enzyme immunoassay. Only the nonexercised DON-fed mice showed significant splenocyte proliferation suppression, 32.9 +/- 17.9% of nonexercised controls (p = 0.021). Exercised controls and DON-fed exercised animals showed splenocyte proliferation of 68-75% of nonexercised controls. Antibody response to a T-dependent antigen, sheep red blood cells, was significantly less for exercised DON-fed mice than in controls (p = 0.031). Serum corticosterone levels were significantly higher for both exercised groups compared to the unexercised groups (p < 0.001). IL-4 secretion from mitogen-stimulated splenocytes was elevated by DON alone (p < 0.05) while IL-2 was elevated by DON with exercise stress (p < 0.05). Our hypothesis was confirmed with respect to T-lymphocyte-dependent antibody production, but not for splenocyte proliferation. Exercise stress abrogated DON-mediated suppression of splenocyte proliferation, perhaps mediated by induction of elevated stress hormones counteracting cytokine expression alterations of DON.     

Immunosuppressive activity of florfenicol on the immune responses in mice

Florfenicol is a new type of broad-spectrum antibacterial that has been used in veterinary clinics. It shows immunosuppressive activity on the immune responses to ovalbumin (OVA) in mice. In the present study, florfenicol suppressed lipopolysaccharide (LPS)-stimulated splenocyte proliferation in a concentration-dependent manner in vitro and in vivo. BALB/c mice were immunized subcutaneously with OVA on days 1 and 4. Following the second immunization, mice were treated with a single daily oral dose of florfenicol (50, 100, and 200 mg/kg) for 10 consecutive days. On day 14, blood samples were collected to analyze OVA-specific IgG, IgG1, and IgG2b antibodies, and splenocytes were harvested to assess lymphocyte proliferation, CD3(+) T and CD19(+) B lymphocyte subsets. The results presented here demonstrate that florfenicol not only significantly suppressed Con A-, LPS- and OVA-induced splenocyte proliferation but also decreased the percentage of CD19(+) B cells in a dose-dependent manner and suppressed CD3(+) T cell at high doses. Moreover, OVA-specific IgG, IgG1 and IgG2b titers in OVA-immunized mice were reduced by florfenicol. These results suggest that florfenicol could suppress humoral and cellular immune responses in mice.     

The Effect of Tp-3 (Arg-Lys-Asp), Tp-4 (Arg-Lys-Asp-Val), and Tp-5 On the Metastatic Capacity of Intravenously Injected Lewis Lung Tumor Cells

The oligopeptides Arg-Lys-Asp (TP-3), Arg-Lys-Asp-Val (TP-4), and Arg-Lys-Asp-Val-Tyr (TP-5) considered as the active short fragments of thymopoietin were administered (lo mg/kg) to C₅₇BI mice 24 hours before the intravenous inoculation of Lewis lung tumor (LLT) cells. A substantial decrease in lung metastasis number was observed as a result of treatment with all of the three oligopeptides. TP-3, TP-4, and TP-5 treatment decreased the immunosuppressive activity of Cyclophosphamid (240 mg/kg) given 96 hours before the inoculation of LLT cells.

After thymectomy, performed eight days before the LLT inoculation, only TP-3 treatment resulted in the decrease of Cyclophosphamid immunotoxicity. A stimulating effect of TP-3 on T helper cell activity is assumed. The oligopeptides TP-3, TP-4, and TP-5 are recommended for clinical trial in case of malignant tumors and immunodeficiency.     

Immunosuppressive Activity of Florfenicol on the Immune Responses in Mice

Florfenicol is a new type of broad-spectrum antibacterial that has been used in veterinary clinics. It shows immunosuppressive activity on the immune responses to ovalbumin (OVA) in mice. In the present study, florfenicol suppressed lipopolysaccharide (LPS)-stimulated splenocyte proliferation in a concentration-dependent manner in vitro and in vivo. BALB/c mice were immunized subcutaneously with OVA on days 1 and 4. Following the second immunization, mice were treated with a single daily oral dose of florfenicol (50, 100, and 200 mg/kg) for 10 consecutive days. On day 14, blood samples were collected to analyze OVA-specific IgG, IgG1, and IgG2b antibodies, and splenocytes were harvested to assess lymphocyte proliferation, CD3⁺ T and CD19⁺ B lymphocyte subsets. The results presented here demonstrate that florfenicol not only significantly suppressed Con A-, LPS- and OVA-induced splenocyte proliferation but also decreased the percentage of CD19⁺ B cells in a dose-dependent manner and suppressed CD3⁺ T cell at high doses. Moreover, OVA-specific IgG, IgG1 and IgG2b titers in OVA-immunized mice were reduced by florfenicol. These results suggest that florfenicol could suppress humoral and cellular immune responses in mice.     

Effects of Phytolacca Acinosa Polysaccharides I with Different Schedules on its Antitumor Efficiency in Tumor Bearing Mice and Production of IL-1, IL-2, IL-6, TNF, CSF Activity in Normal Mice

Effects of Phytolacca acinosa polysaccharides I (PAP-I), 5^∼ 40 mg/kg in timing of 7 times/wk, 3 times/wk and 1 time/wk on their antitumor efficiency in Sarcoma-180 bearing mice were comparatively investigated. The results confirmed that PAP-I (10 mg/kg, 3 times/wk) reached its optimal antitumor efficiency. Concanavalin A-, lipopolysaccharides-induced lymphocyte proliferation and the IL-2 production were tested in normal mice which were treated with PAP-I, 5^∼50 mg/kg in timing of 1 time/wk and 3 times/wk. The results showed that PAP-I could augment lymphocyte proliferation and IL-2 production in the group treated with PAP-I in timing of once a week. However, in the group 3 times/wk, PAP-I could significantly weaken lymphocyte proliferation and IL-2 production. Further studies on IL-1, TNF and IL-6 secreted from macrophages and the level of CSF activity in serum of normal mice with different schedules showed that PAP-I (10 mg/kg, 3 times/wk) was the best one in regulating the production of IL-1, TNF, IL-6 and CSF activity. M-CSF was confirmed in the serum by using monoclonal antibody of IL-3, GM-CSF and polyclonal antibody of M-CSF. These results suggested that the antitumor effect of PAP-I, may be mainly related to its augmenting effect on macrophages in mice.     

卵白蛋白诱导哮喘小鼠脾细胞增殖中STAT5的变化

目的 :研究卵白蛋白 (OVA)在哮喘小鼠脾细胞增殖中信号转导蛋白和转录激活因子 5 (STAT5 )的变化 ,探讨STAT5在OVA诱导哮喘小鼠脾细胞增殖中的作用。方法 :经腹腔注射与雾化吸入OVA诱发小鼠哮喘发作。激发后分离小鼠脾细胞 ,采用MTT比色法测定经OVA诱导的脾细胞增殖 ;用双染免疫组化法检查脾细胞中STAT5磷酸化与STAT5抗原的定位。用电泳迁移率变动分析 (EMSA)测定STAT5与DNA探针的结合力。结果 :OVA在体外能明显诱导哮喘小鼠脾细胞增殖 (平均A值为 0 .5 4 3± 0 .112 ) ,呈剂量依赖性 ,与对照组相 (平均A值为 0 .2 0 3± 0 .0 32 )比较差异明显 (P <0 .0 1)。OVA诱导 1、3h ,能诱导哮喘小鼠脾细胞中的STAT5磷酸化 ,脾细胞中出现STAT5 DNA结合带。结论 :OVA能诱导哮喘小鼠脾细胞增殖和脾细胞中的STAT5磷酸化 ,增加STAT5与DNA探针的结合力 ,说明STAT5信号途径在OVA诱导的哮喘小鼠脾细胞增殖中起重要作用     

Immune alterations in three mouse strains following 2-deoxy-D-glucose administration

Using 2-deoxy-D-glucose (2-DG)-induced stress, our laboratory has developed studies to define stress effects on immune responses. Here, we report effects of increasing doses of 2-DG on the immune response of BALB/c, C57BL/6 and BDF(1) mice 2 h after three injections of 0 to 2000 mg/kg of 2-DG. Female 4- to 5-week-old mice were euthanized and blood and spleens were collected. A suspension of partially purified mature T splenocytes was obtained by negative selection using J11.d2 antibodies. Glucose and corticosterone levels were measured in the plasma of each mouse. Splenocyte and mature T splenocyte suspensions were tested in in vitro proliferation assays with or without concanavalin A. Splenocytes were analyzed for the following cell-surface markers: CD3, TCR alpha/beta, CD4, CD8 and major histocompatibility complex (MHC) Class II. Significant increases in blood glucose levels were observed in C57BL/6 and BALB/c strains with the highest 2-DG dose (p<0.05). Corticosterone levels were higher in BDF(1) mice and C57BL/6 mice following the administration of 1000 and 2000 mg/kg of 2-DG, respectively (p<0.01). In vitro proliferation of mature T splenocytes in the presence of concanavalin A was decreased in BDF(1) (p<0.05) but not in BALB/c and C57BL/6 mice. In addition, in BDF(1) mice the decrease was highly correlated with an increase of CD3+ and TCR alpha/beta+ cells in the spleen. These results demonstrated high variability in the response of different mouse strains to 2-DG-induced stress.     

Immunotoxicity induced in mice by subacute exposure to berberine

The immunotoxic effects of the isoquinoline alkaloid berberine (BBR) were investigated in Balb/c mice. Here, BBR was administered daily by intraperitoneal injection at doses of 5 and 10?mg/kg for 14 days. Following the exposure, host spleen weight, cellularity and histopathology, as well as delayed-type hypersensitivity (DTH) responses, hemagglutination titers (HA), spleen cell subtype profiles, splenocyte cytokine production and lymphocyte proliferation were studied in all of the test groups of animals. The results showed that the high dose of BBR (10?mg/kg) could suppress both cellular and humoral immune functions in the treated hosts. BBR at 5?mg/kg only appeared to impact on DTH responses and lymphoproliferation. Based on the finding here, it would seem that BBR has effective immunosuppressive properties. Mechanistic studies are required to determine exactly how this material is acting to impart many of the immunotoxic effects demonstrated here. At the same time, further research should also be performed on BBR to further develop its potential use as an effective immunosuppressant or co-adjuvant for the treatment of diseases caused by an exaggerated or unwanted immune response.