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1.
This study examined the effect of long-term administration of low-dose FTY720 on survival of murine cardiac allograft and the possible mechanism. Murine models of abdominal heterotopic heart transplantation were established. Low-dose FTY720 (0.3 mg/kg) was administrated to the animals 4 days before the transplantation of cardiac allografts until the occurrence of rejection or the observation terminals. The animals without FTY720 treatment and those with syngeneic cardiac grafts transplanted served as controls. The mean survival time (MST) of grafts, and T lymphocyte subsets in grafts, periph-eral blood and lymphoid organs were measured by histopathological examination or flow cytometry, and compared among groups. The results showed that the MST of allografts in FTY720-treated mice was more than 40 days, significantly longer than that in the untreated group (MST=8 days, P<0.01). After the long-term administration of FTY720, the proportion of CD4+ and CD8+ lymphocytes in pe-ripheral blood was diminished significantly, but the proportion of CD4+ lymphocytes was increased in mesenteric lymph nodes (MLNs) and spleen. Immunofluorescence staining revealed that the infiltration of CD4+ and CD8+ lymphocytes in allografts was significantly inhibited after long-term administration of low-dose FTY720. It was concluded that low-dose long-term administration of FTY720 could pro-mote T lymphocytes in lymphatic organs and decrease their infiltration in allografts, resulting in the in-hibition of rejection and the long-term survival of allografts.  相似文献   

2.
Objective To investigate the role of anti- interleukin-2 receptor(CD25) monoclonal antibody in the regulation of cytokine mRNA expression of IL-1β, IL-2, CD25, IL-4, IL-5, IL-6, IL-10, tumour necrosis factor-α (TNFα), and interferon-γ (IFNγ) in cardiac allografts to elucidate its immunological mechanism and role in rats that have undergone cardiac transplantation. Methods These in vivo studies were conducted using a rat MHC mismatch SD to Wistar heterotopic cardiac transplant model. Simulect, an anti-CD25 antibody, was used to prevent allograft rejection. An increase in the rate of allograft survival was observed. Rats were sacrificed on day 1, 3, 5, 7, 9, 11, 14 post-transplantation and hearts were harvested for furgher study. Cytokine mRNA expression was determined by semiquantitative RT-PCR. Results In the control group, cardiac allografts were rejected at 8.3±1.7 days after transplantation (mean±s).The rats who received CsA rejected the cardiac allograft at 26.4±5.7 days post-transplant. Allograft survival of Simulect-treated rats was 29.2±7.1 days (P&lt;0.05 vs controls). Rats treated with simulect and CsA had the longest survival of 55.0±11.6 days (P&lt;0.001 vs controls). CD25 mRNA expression in the heart tissue samples of treated rats was undetectable or very weak. However, the untreated group, CD25 expression increased, although anti-CD25 decreased this CD25 expression in the heart graft. Furthermore, in untreated allografts, IL-2, TNFα and IFN-γ were strongly expressed, an effect that markedly decreased after simulect treatment. Finally, IL-4, IL-5, IL-6 and IL-10 expression was strong in anti-CD25-treated allografts. Conclusions These results suggest that anti-CD25 antibody treatment may not only neutralize CD25 activity but also play a role in altering cytokine mRNA expression and prolong the survival of allografts.  相似文献   

3.
Background This study was to evaluate whether anergic cells induced by the blockade of CD40-CD154 and CD28-B7 costimulatory pathways can act as potent immunoregulatory cells in vitro and prolong cardiac allograft survival after adoptive transfer.Methods Anergic cells were induced in vitro by the addition of anti-CD154 and anti-CD80 monoclonal antibodies (mAbs) to primary MLR (mixed lymphocyte reaction) consisting of BALB/c as responder and C3H as stimulator. Anergic cells were added to a newly formed MLR in assessing the regulatory capacity and antigen specificity of anergic cells. The ability of anergic cells to respond to antigen and/or exogenous recombinant mouse interleukin-2 (rmIL-2) was tested. For in vivo studies, anergic cells were intravenously injected into 3.0-Gy γ-irradiated BALB/c mice immediately after heterotopic abdominal cardiac transplantation. To prolong allograft survival, recipient mice injected with anergic cells received rapamycin therapy [1 mg·day(-1)·kg(-1)].Results Anergic cells strongly suppressed the proliferation of naǐve BALB/c splenocytes against the original (C3H) stimulator in a dose-dependent manner, but they failed to suppress the proliferation of naǐve BALB/c splenocytes against the third-party (C57BL/6J) stimulator. The anergic state was reversed by both original (C3H) stimulator and additional exogenous IL-2. In in vivo studies, untreated irradiated BALB/c mice rejected C3H cardiac allografts with a mean survival time of (8.6±1.1) days, whereas those injected with the anergic cells rejected the allografts with a mean survival time of (11.8±1.9) days, which was slightly longer than that of the untreated mice. The protocol based on anergic cells injection plus rapamycin therapy could prolong allograft survival significantly [(29.6±4.4) days]. Conclusions Anergic cells induced by the blockade of CD40-CD154 and CD28-B7 costimulatory pathways can act as potent immunoregulatory cells in vitro, and prolong cardiac allograft survival after adoptive transfer in the presence of rapamycin therapy. This procedure might be clinically useful for prolonging allograft survival if optimal protocols are developed.  相似文献   

4.
Objective The present paper aims to investigate the effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and N-nitrosodiethylamine (DEN) on tumorigenesis and its potential mechanism. Methods The potentials of TCDD and DEN in separation or in combination to induce malignant transformation were tested in Balb/c 3T3 cells by using a cell transformation assay method. The possible mechanism of observed effects was studied further by adding α-naphthoflavone (α-NF), a competitive binding agent of TCDD, to the Aryl hydrocarbon receptor (AhR) pathway. The mRNA expressions of Cyp1a1 and Cyp2a5 gene in Balb/c 3T3 cells treated by DEN and TCDD in separation or in combination with or without presence of α-NF were measured with fluorescence quantification RT-PCR technique. Results The cell transformation frequency (TF) was significantly higher in case of induction with TCDD in combination with DEN, as compared to that with either TCDD or DEN alone. These effects were not inhibited via α-NF. The mRNA expression levels of both Cyp1a1 and Cyp2a5 were enhanced by TCDD treatment alone, but this inducible effect was blocked in cells treated by TCDD and DEN in combination. Conclusion TCDD and DEN had a significant synergistic effect on tumorigenesis when they were used in combination. AhR pathway may not be the key mechanism of this synergistic effect. Thus, it is necessary to further test the potential mechanism involved in cancer development.  相似文献   

5.
In order to investigate the origin of neointimal smooth muscle cells in transplant arterio- sclerosis in rat aortic allograft, sex-mismatched bone marrow transplantation was performed from male Wistar rats to female Wistar rats. Four weeks after transplantation, the aortic transplant model was established by means of micro-surgery in rats. The recipients were divided into 4 groups: female Wistar-female Wistar aortic isografts, female SD-female Wistar aortic allografts, male SD-male Wis- tar aortic allografts, female SD-chimera Wistar aortic allografts. Eight weeks after transplantation, aortic grafts were removed at autopsy and processed for histological evaluation and immunohisto- chemistry. The results indicated that excessive accumulation of α-SMA-positive smooth muscle cells resulted in significant neointima formation and vascular lumen stricture in rat aortic allografts. Neointima assay revealed that the neointimal area and NIA/MA ratio of transplanted artery were sig- nificantly increased in all of aortic allograft groups as compared with those in aortic isograft group (P<0.01). Neointimal smooth muscle cells were harvested from cryostat sections of aortic allograft by microdissection method. The Sry gene-specific PCR was performed, and the result showed that a dis- tinct DNA band of 225 bp emerged in the male-male aortic allograft group and chimera aortic al- lograft group respectively, but not in the female-female aortic allograft group. It was suggested that recipient bone-marrow cells, as the origin of neointimal smooth muscle cells, contributed to the pathological neointimal hyperplasia of aortic allograft and transplant arteriosclerosis.  相似文献   

6.
Objective: To study the synergistic effect of ICOS-Ig combined with cyclosporine (CsA) on mouse heart transplantation and explore its therapeutic potential. Methods: ICOS-Ig fusion protein was generated by fusing the extraeellular portion of human ICOS and Fc portion of human IgG. To investigate the effect of ICOS-Ig on T-cell proliferation in vitro, ICOS-Ig or IgG was added to the primary MLR cultures (BALB/c spleen T cells as responder cells and irradiated C57BL/6 spleen cells as stimulator cells). The cells responsiveness rates were detected by 3H-TdR methods. Then the T cells of each group in primary MLR were cultured as responder cells for secondary MLR, and irradiated C57BL/6 (donor) or C3H (third party) spleen cells as stimulator cells. To study the effect of ICOS-Ig on T-cell proliferation in vivo, CFSE-labeled C57BL/6 spleen cells were transferred to irradiated BALB/c mice. Mice were then treated with IgG, ICOS-Ig or CsA. Seventy two hours after transfer, the spleen cells of the mice were harvested for the detection of CD4^+CFSE^+ and CD8^+CFSE^+ by FACS. C57BL/6 mouse underwent transplantation of the hearts of BALB/c mouse and were then randomly divided into five equal groups: no treatment group, control lgG treated group (250 gg i.p. d2, 4, 6), ICOS-Ig treated group (250 μg i.p. d2, 4, 6), CsA treated group (10 mg/kg i.p. d0-6), ICOS-Ig combined with CsA group. The cardiac allograft survival was monitored by daily palpation. Results: In primary MLR, ICOS-Ig inhibited T-cell proliferation, (inhibition ratio 58i8.2% in 50 μg/ml). In secondary MLR, ICOS-Ig specifically inhibited donor spleen cells, which suggested ICOS-Ig could induce donor-specific hyporesponsiveness. In the CFSE dye assay, CD4^+CFSE^+ and CD8^+CFSE^+ in ICOS-Ig and CsA group was stronger than those in control group, which showed ICOS-Ig and CsA could inhibit the proliferation of allo-reactive T cells in vivo. In mouse heart transplantation model, survival was significantly prolonged in animals treated with ICOS-Ig or CsA as compared with controls. Moreover, ICOS-Ig combined with CsA group had even longer engraftment (〉100 d) than ICOS-Ig or CsA used alone. In histological examination, it was found that there were congestions and edemas in no treatment and IgG treated recipients, together with a lot of inflammatory cells infiltrated. Allogeneic hearts from ICOS-Ig and/or CsA immunized recipients revealed milder histological changes. It was revealed in mechanical analysis that splenic T cells from recipients also exhibited depressed mixed leukocyte reactions (MLR) and cytotoxic lymphocyte reactions (CTL). Conclusion: These data suggest that ICOS-Ig combined with CsA induces a long-term survival of mouse cardiac allografts, whereas monotherapy is less effective in this regard. Thus, ICOS-Ig combined with CsA treatment may be a novel regimen to combat allograft rejection.  相似文献   

7.
The activation of T cells to differentiate and to proliferate is an essential step in the immune response to antigen, especially in cell-mediated acute allograft rejection. Besides the interaction of CD3/TCR complex with Ag/MHC complex presented on antigen-presenting cells, a complete T-cell activation and proliferation requires a second costimulatory signal. The interaction of CD28/CTLA-4 and B7 is a major costim-ulatory pathway for T Cell activation. Inhibition of this pathway results in development of antigen-specific unresponsiveness and clonal anergy. In present study, the biologic function of anti-CD28 monoclonsl anti-body and its Fab fragment were investigated in vitro and in viro. The results indicate that mAbCD28 and its Fab fragments could promote the functional recovery of allografts and prolong the graft suvival, but could not reverse the acute rejection or induce transplantation tolerance in the rat PTG allograft model. We also found that peripheral TNF-α level and NK-cell activity were suppressed in the presence of mAbCD28 and its Yab fragments for s relatively long time after PTG transplantation.  相似文献   

8.
Background Immune rejection is the main reason of grafts failure after corneal transplantation. This study was to determine whether interlerkin-1 receptor antagonist (IL-1ra) eye drops could prolong corneal allografts survival in high-risk corneal orthotopic allotransplantation in rat model and to study the effect of IL-1ra on the expression of CD1-positive cells in the grafts. Methods For all experiments, the Sprague-Dawley (SD) rats’ corneas were transplanted into Wistar rats’ eyes. High-risk transplants included those that had been sutured into Wistar recipient beds with corneal neovascularization induced by placement of three interrupted sutures in the host cornea 7 days earlier. All the animals were divided, in a masked fashion, into three treatment groups and one control group. Each treatment group received IL-1ra eye drops of different concentrations (1 mg/ml, 3 mg/ml, or 5 mg/ml, respectively) four times a day for 30 days. The control group received 0.9% normal saline (NS) eye drops in the same way as the treatment groups. All allografts were evaluated for signs of rejection from the first day after surgery. Ten days later, corneal specimens were processed to examine the expression of CD1-positive cells and histopathological changes. Results The survival time of the transplants was 5.80±0.79, 5.89±1.05, 6.78±0.83, and 9.00±2.36 days respectively in the control or three treatment groups. Compared with the control group, 1 mg/ml IL-1ra eye drop did not prolong the survival time of the allografts (t=0.210, P&gt;0.05). However, 3 mg/ml and 5 mg/ml IL-1ra eye drop did prolong the survival time of the grafts (t≥2.627, P&lt;0.05), with the latter showing more obvious effect. Immunohistochemical examinations showed a significant decrease in inflammatory cell and CD1-positive cell infiltration in IL-1ra treated groups compared with the control group. Conclusions IL-1ra can promote corneal allograft survival in a dose-dependant manner by reducing the infiltration of CD1-positive cells in high-risk corneal transplantation.  相似文献   

9.
Objective To explore the diagnositc role of heat shock protein ( HSP) 70 in acute rejection after pancreatioduodenal transplantation in rats. Methods Groups of Wistar rats underwent total pancreatioduodenal transplantation from allogeneic SD or syngeneic Wistar rats. The grafts were harvested on the posttransplantation day 3,5 and 7 and were used to detect the expression of HSP70 by immunohistochemistry and Western Blotting quantitative methods. The correlation between HSP70 expression and pathological findings was observed. Results The level of HSP70 in the isografts did not change greatly( P > 0.05); the level of HSP70 in the allografts was increased progressively on the posttransplantation day3, 5 and 7 ( P < 0.01). There was a significant correlation between HSP70 and pathological score in the allograft group (P < 0.01, r = 0.934). Conclusion HSP70 involved in pancreas allograft rejection and could be useful for early diagnosis of acute rejection following pancreas transplantation. 8 refs,2 tabs.  相似文献   

10.
To investigate the gene expression profiles in acute allograft rejection of renal transplantation, and identify the markers for the early diagnosis of acute rejection, heterotopic kidney transplantation was performed by using F344 or Lewis donors and Lewis recipients. No immunosuppressant was used. Renal grafts were harvested on days 3, 7, and 14. A commercial microarray was used to measure gene expression levels in day-7 grafts. The expression levels of 48 genes were up-regulated in the allograft in comparison with the isograft control, and interferon-γ-induced GTPase gene was most significantly up-regulated in allografts. It is concluded that a variety of pathways are involved in organ transplant rejection which is dynamic and non-balanced. IFN-inducible genes, such as IGTP, may play an important role in the rejection. A lot of important factors involved in acute rejection are unnecessary but sufficient conditions for the rejection. We are led to conclude that it is virtually impossible to make an early diagnosis based on a single gene marker, but it could be achieved on the basis of a set of markers.  相似文献   

11.
近年新生儿、婴儿、成人麻疹患者逐年增加,临床表现一般仍较典型,成年人麻疹患者全身中毒症状较重。麻疹抗体检测结果阳性是主要的诊断依据。麻疹发病的双相移位的机理可能是,免疫保护力不足,婴儿出生时麻疹抗体力低。孕期母传胎的麻疹抗体减弱,母经乳汁传给婴儿的抗体减弱,成人麻疹抗体水平逐年下降。预防措施是怀孕前给予育龄妇女麻疹疫苗接种,鼓励母乳喂养,麻疹疫苗计划免疫适当提前,在成人追加麻疹疫苗的免疫,加强病毒变异的研究等。  相似文献   

12.
目的以研究方法LiPA(Line Probe Assay)分析VacA等位基因的表达,了解幽门螺旋杆菌致病机理的理解。方法从三个不同城市87位进行胃镜检查患者的胃粘膜中培养出幽门螺旋杆菌,提取DNA,用LiPA方法分析VacA等位基因。结果(1)87位患者以sic(88.5%)和m2a(63.2%)分布为主,未发现s1b和s2;(2)混合菌株感染率为41.4%,远远高于西方国家,其中上海的混合感染率最高(62.5%),与北京(41.0%)和南宁(20.8%)相比具有显著性差异,P〈0.01;(3)北京、海、南京三个不同城市s1、m等位基因亚型分布率存在差异;(4)溃疡病和非溃疡病患者m1和m2的分布率没有显著性差异。结论我国幽门螺旋杆菌多重菌株感染率较高,不同的m基因型与消化性溃疡的发生无显著性相关。  相似文献   

13.
《中国现代医生》2019,57(36):77-79
目的探讨对上颌骨牙源性囊肿患者进行囊肿彻底刮除手术的临床疗效。方法对我科在2010年1月~2017年9月收治的73例上颌骨牙源性囊肿患者行囊肿彻底刮除手术治疗,对患者术区肿胀消退、术后伤口感染、伤口愈合、牙龈再附着、术后复发、骨质改建、骨质修复等情况随访观察。结果 73例患者术后肿胀消退时间为1~4 d。73例患者术后均未发生伤口感染,伤口均一期愈合。所有患者牙龈再附着情况好,术后均未见复发。术后未见并发症。骨质改建效果好,骨质修复的效果因影像学资料过少,缺乏客观依据,暂不下有效结论。结论对上颌骨牙源性囊肿患者进行囊肿彻底刮除手术,术后患者的恢复情况良好,值得在临床治疗上进行推广。  相似文献   

14.
尿液pH值对红细胞检验影响的探讨   总被引:2,自引:1,他引:1       下载免费PDF全文
[目的 ]通过尿液 pH值对红细胞检验影响的观察 ,更加科学、准确地诊断血尿和血红蛋白尿。[方法 ]采用干化学分析仪检测和尿液显微镜红细胞计数 ,观察 180例正常人尿标本加入正常人血标本后 ,不同 pH值 ,不同时间内 ,观察红细胞溶解情况。 [结果 ]pH <5 .5以下时 ,随着时间的延长 ,红细胞溶解现象明显。 1h后观察有显著性差异 (P <0 .0 5 ) ;2h后有非常显著性差异 (P <0 .0 1)。[结论 ]pH <5 .5时对红细胞计数影响较大 ,易致红细胞发生溶解现象 ,出现假性血红蛋白尿 ,对血尿和血红蛋白尿很难区分 ,给临床诊断造成不便 ,更易引起漏诊和误诊。  相似文献   

15.
目的:提高十二指肠损伤的诊治水平,方法:回顾总结该院1999年-2001年间收治的十二指肠损伤7例临床经验。结果:合并其他腹部脏器损伤86%(6/7),单纯十二指肠损伤14%(1/7)。损伤部位以十二指肠降部为多占71%(5/7),水平部和球部各占14%(1/7),术后并发症发生率28%(2/7)、病死率14%(1/7)。结论:掌握十二指肠损伤的特点,早诊断、早手术、术中认真探查,掌握好检查指征,选择合理恰当术式,加强术后管理,可提高治愈率。  相似文献   

16.
醋柳黄酮缓释片的药动学初步研究   总被引:1,自引:0,他引:1  
目的:研究醋柳黄酮缓释片在家犬体内的药动学过程,测定其药动学参数,计算缓释片相对于普通片的生物利用度。方法:将实验动物分为两组,分别用醋柳黄酮缓释片和普通片进行口服给药,用高效液相色谱法测定血浆药物浓度,应用3P97软件求算药动学参数。结果:醋柳黄酮缓释片及普通片的tm ax分别为4.87 h和2.87 h,Cm ax分别为每小时0.46μg.L-1和每小时0.56μg.L-1,缓释片的相对生物利用度为111.7%。结论:醋柳黄酮缓释片与普通片均符合一室模型,缓释片与普通片具有生物等效性,且醋柳黄酮缓释片有明显的缓释效果。  相似文献   

17.
目的解决腰椎间盘突出症手术中神经压迫。方法对1980~1998年再手术资料进行统计分析,讨论分析再手术原因,再次手术前影像学检查,观察病理变化以确定再手术方法。结果对11例随访6个月~1年,优7例(68.4%),良3例(36.8%),差1例(2.8%)。结论初次手术前详细查体和分析X线片,术中用导尿管和神经剥离探查,尽量避免髓核遗留,手术范围不宜太大,尽量减少对软组织和脊柱结构的破坏,避免形成硬膜囊与神经根粘连而致单纯形疤痕。  相似文献   

18.
扩张兔皮肤超微结构的变化   总被引:4,自引:4,他引:0  
目的:动态观察扩张兔皮肤超微结构的变化。方法:选用2--3kg新西兰大白兔64只,分为2大组,快速扩张组和常规扩张组,每组32只,每大组再分为4组,为扩张完成后即时、1周、12周、24周组。每组8只,其中4只为实验组,另4只植入扩张器不扩张作为对照组。透射电子显微镜观察各组皮肤超微结构的变化。结果:表皮扩张后经历--由扩张刺激引起的创伤至完全修复的过程。扩张后即时真皮中成纤维细胞大量增生,功能由静止转向活跃,胶原纤维碎裂成片,弹力纤维部分断裂,炎症细胞浸润;扩张后1周常规扩张组基底膜连续性基本恢复。显示成纤维细胞合成功能活跃。扩张后12周、24周,成纤维细胞趋于稳定、形态狭长,部分胶原排列紊乱,部分有似癜痕样改变。结论:扩张刺激可致兔皮肤创伤。扩张后真皮不可完全修复。  相似文献   

19.
目的观察芹黄素对大鼠缺血视网膜功能恢复的作用。方法30只Long-Evans大鼠用动脉结扎法造成视网膜缺血模型,其中治疗组20只腹腔注射芹黄素,对照组10只注射溶媒二甲基亚酚。用视觉电生理仪检查视网膜功能恢复情况。结果芹黄素治疗组视网膜功能恢复明显好于对照组(P<0.05)。结论芹黄素能促进大鼠缺血视网膜的功能恢复。  相似文献   

20.
阴道炎1236例病原检查分析   总被引:1,自引:0,他引:1  
对1236例阴道炎患者的阴道分泌物作直接镜检和病原菌分离培养检查;结果,细菌感染900例,念珠菌234例,滴虫102例。900例细菌经鉴定;葡萄球菌300例,阴道加特纳菌276例,淋病奈瑟菌170例,其它细菌124例。结果表明,葡萄球菌,阴道加特纳菌,淋病奈瑟菌是细菌性阴道炎最常见的致病菌。  相似文献   

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