大鼠DCs单抗和雷公藤多甙对大鼠同种异体心肺联合移植排斥反应的影响

采用改良的大鼠同种异体心肺联合移植手术，研究了大鼠树突状细胞（ＤＣｓ）单克隆抗体单独和联合雷公藤多甙片对移植排斥反应的影响，并与生理盐水对照组、雷公藤多甙片（ＴⅡ）组进行比较。结果表明：大鼠ＤＣｓ单抗单独和联合ＴⅡ两治疗组间无明显区别，但两组大鼠移植心脏存活时间明显长于生理盐水组和ＴⅡ组（Ｐ＜００１）；而且病理切片显示以慢性排斥反应改变为主。而生理盐水对照组和ＴⅡ组皆表现为急性排斥反应。提示ＤＣ单抗在治疗移植排斥反应中有实用价值。     

大鼠DCs单抗和雷公藤多甙对大鼠同种异体心肺联合移植排斥？…

采用改良的大鼠同种异体心肺联合移植手术，研究了大鼠树突状细胞（ＤＣｓ）单克隆抗体单独和联合雷公藤多甙片对移植排斥反应的影响，并与生理盐水对照组、雷公藤多甙片（ＴⅡ）组进行比较，结果表明：大鼠ＤＣｓ单抗单独和联合ＴⅡ两治疗组间无明显区别，但两组大鼠移植心脏存活时间明显长于生理盐水和ＴⅡ组（Ｐ〈０．０１）；而且病理切片显示以慢性排斥反应改变为主。而生理盐水对照组和ＴⅡ组皆表现为急性排斥反应。提示ＤＣ单     

细胞因子移植排斥反应

急性器官移植排斥反应时，多种细胞因子血清水平呈现升高现象，但需要与感染及ＣＭＶ等因素引起的细胞因子变化鉴别。移植物局部以ＩＬ－１，ＴＮＦ及Ｍ－ＣＳＦ升高为明显，ＩＬ－２，ＩＬ－３，ＩＬ－４，ＩＬ－６，Ｇ－ＣＳＦ或ＧＭ－ＣＳＦ未见升高。实体器官排斥时ＩＬ－４ｍＲＮＡ，ＩＬ－２ｍＲＮＡ及ＩＬ－５ｍＲＮＡ表达可升高。而炎性因子ＩＬ－１βｍＲＮＡ，ＩＬ－６ｍＲＮＡ及ＴＮＦａｍＲＮＡ表达不升高。某些细胞因子     

移植前诱导抗独特型抗体对小鼠皮肤排斥反应的抑制作用

目的 探讨抗独特型抗体诱导对异品系小鼠皮肤移植排斥反应的影响。方法 以C57BL／6小鼠脾细胞免疫Balb/c小鼠制备抗同种异品系抗体（Ab1),将Ab1与KLH交联后，免疫Balb/c小鼠诱导产生抗独特型多克隆抗体（Ab2),并以之为受体，观察Ab2对小鼠皮肤移植排斥反应的影响。结果Ab1交联KLH加弗氏佐剂免疫可有效地诱导抗独特型抗体（Ab2)产生。与对照组相比较，Ab2诱导组小鼠移植物存活时间明显延长。结论 移要有在受体体内诱导产生以移植物抗原为模拟抗原的抗独特型抗体，可对移植排斥反应产生有效的抑制作用。     

落新妇甙对肝缺血再灌注损伤的保护作用

背景：肝脏是对缺血再灌注损伤最敏感的器官之一。黄酮类化合物落新妇甙可作为递氢体清除氧自由基,从而可能在减轻肝脏缺血再灌注损伤等方面发挥作用。 目的：观察落新妇甙对肝脏热缺血再灌注损伤的保护作用,对其机制进行初步探讨。 方法：C57BL/6小鼠随机分为4组：假手术组、模型组、小剂量干预组和大剂量干预组。干预组小鼠于缺血前24 h和1 h分别给予10或40 mg/kg的落新妇甙腹腔注射,然后建立70%部分肝缺血再灌注模型。采集血液和肝脏组织样本。检测血清丙氨酸氨基转移酶活性,ELISA测血清肿瘤坏死因子α水平,化学比色法测定肝组织中超氧化物歧化酶、丙二醛含量。肝脏组织病理学检测。Westernblot检测肝组织中肿瘤坏死因子α蛋白含量,RT-PCR检测肿瘤坏死因子α mRNA。 结果与结论：落新妇甙干预能有效降低血清丙氨酸氨基转移酶水平,干预组肝组织丙二醛含量较模型对照组明显下降(P < 0.01);而超氧化物歧化酶含量明显上升(P < 0.01);干预组血清肿瘤坏死因子α含量较模型组对照组明显下降(P < 0.01);小、大剂量干预组肝组织中肿瘤坏死因子α蛋白表达与模型组模型对照组比较渐次降低,与半定量RT-PCR结果相符(小剂量干预组P < 0.05,大剂量干预组P < 0.01)。落新妇甙保护肝脏热缺血再灌注损伤显示出剂量-效应关系趋势。结果提示,落新妇甙干预能减轻小鼠肝脏热缺血再灌注损伤后的炎症反应和脂质过氧化损伤,有效改善肝功能和肝脏病理损害;机制可能在于其能抑制缺血再灌注损伤肝组织中肿瘤坏死因子α的高表达。     

器官冻存与移植排斥反应

液氮超低温冻存器官不仅能达到长期保存的目的 ,而且能杀伤某些低温敏感免疫细胞及组织细胞 ,显著降低移植后免疫排斥反应。本文以冻存胰岛、心脏瓣膜和皮肤为例 ,阐述器官冻存对移植排斥反应的影响。     

调节性T细胞在大鼠小肠移植急性排斥反应中的作用

目的 分析调节性T细胞在大鼠急性排斥反应中的作用。方法 采用免疫组化SABC染色法，测定BN→LEW大鼠小肠移植急性排斥反应时，外周血及移植肠浸润淋巴细胞中调节性T细胞：CD4^ ,CD8^ ,CD25^ T淋巴细胞及相关细胞因子IL－4和IFN－γ的表达，并与同基因大鼠间小肠移植（BN→BN）作比较。结果 外周血淋巴细胞分析显示，大鼠小肠移植急性排斥反应时，以CD4^ ,CD25^ ,T细胞为主，CD8^ 淋巴细胞只占少部分；分泌IL－4的细胞在术后4，7，14d分别只占14．3％，16．2％和16．9％。移植肠基底浸润的淋巴细胞以CD4^ ,CD25^＋和分泌IFN－γ的淋巴细胞为主。结论 在大鼠同种小肠移植中，急性排斥反应与CD25^ ,CD4^ T细胞及Th1相关细胞因子IFN－γ的表达增加相关。而CD8^＋T淋巴细胞和Th2相关细胞因子IL－4可能具有保护作用。     

慢性排斥与移植耐受

防止慢性排斥和诱导移植耐受是当今移植临床的重大难题，本文概述了两者的机制和联系，展望了这一领域的研究前景。     

新免疫抑制剂雷帕霉素抗移植排斥作用的实验研究

作者研究了雷帕霉素（rapamycin;RPM）对C57BL/6J→BALB/c小鼠心肌和皮肤移植的抗移植排斥作用,结果表明 RPM比目前应用于临床器官移植的环孢菌素（Cyclosporine A;CsA）具有更好的抗移植排斥作用。此外还观察了 RPM对正在进行的移植心肌排斥反应的作用,RPM于小鼠心肌移植后第 7天开始给药与0天开始给药组相比较,移植心肌的平均存活天数无明显差异,表明RPM对心肌移植排斥反应有很好的治疗作用。小剂量的RPM与亚治疗剂量的CsA合用还有很好的协同作用。     

大鼠皮肤移植排异反应中T淋巴细胞亚群的观察

为了了解在皮肤移植组织排异反应中浸润的不同T淋巴细胞亚群 ,分析其与排异反应的关系。采用HE及免疫组化方法观察大鼠III度烫伤后 2 0例同种异体 自体皮肤混合移植和 15例大张同种异体皮肤移植组织在移植后 4或 5、 7、 14、 2 1和 2 8d时CD4+ 和CD8+ 淋巴细胞的比例。结果表明同种异体 自体皮肤混合移植组 7～ 14d时CD8+ 淋巴细胞明显高于大张同种异体皮肤移植组 (P <0 0 5 ) ,在移植后 4或 5dCD4+ 淋巴细胞明显高于CD8+ 淋巴细胞。大张同种异体皮肤移植组在移植后 7～ 14dCD4+ 淋巴细胞明显高于CD8+ 细胞 ,在植皮后 7～ 2 8d高于同种异体 自体皮肤混合移植组 ,2 1d时差异有统计学意义 (P <0 0 5 )。在 7～ 14d时CD4/CD8比值高于同种异体 自体皮肤混合移植组 (P <0 0 5 )。提示同种异体 自体皮肤混合移植排异反应以CD8+ 淋巴细胞为主 ,而在大张同种皮肤移植排异反应中CD4+ 淋巴细胞起主要作用。     

T Cell Receptor Excision Circles (TRECs) in Relation to Acute Cardiac Allograft Rejection

The purpose of this study was to quantify T cell receptor excision circles (TRECs) in blood mononuclear cells of cardiac transplant recipients and to investigate a possible relationship between TREC levels and rejection episodes. In addition, we investigated the correlation of TREC levels with age and also compared the levels between transplant recipients and healthy individuals. TREC levels were assessed by quantitative competitive PCR in 70 blood samples from 27 graft recipients and in 66 blood samples from 66 healthy individuals. The results showed: (1) higher TREC levels during rejection than during rejection-free periods (medians 9.0 vs. 0.3; p<0.001); (2) no suggestion of correlation with doses of prednisone or time after transplantation; (3) a negative correlation between TREC levels and age; and (4) lower TREC levels in cardiac recipients than in age-matched healthy controls. The value of blood TREC level measurements as an approach to rejection monitoring warrants future investigation.     

Involvement of Fas-Fas Ligand Interactions in Graft Rejection

The Fas/Fas ligand (FasL) pathway has been shown to be important in T lymphocyte- mediated cell death and is a key peripheral immunoregulatory mechanism that limits expansion of antigen-activated lymphocytes. The expression of Fas by commonly transplanted organs such as the heart, lung, kidney, and liver suggests that these tissues may be targets of FasL-expressing allospecific cytotoxic T lymphocytes. In this review the current literature examining the Fas/FasL system as a potential cellular effector pathway in tissue injury is discussed. In addition to a deleterious role in destruction of graft tissue, Fas/FasL interactions may have a beneficial role in transplantation. Recent studies suggest that modulation of FasL in target tissue leads to deletion, via apoptosis, of graft infiltrating lymphoid cells. However, an equally compelling series of reports indicate that overexpression of FasL can lead to a heightened immune response. These data are reviewed in the context of strategies to achieve long term allograft survival.     

Monocyte Chemoattractant Protein-1 (MCP-1/CCL2) Levels and Its Association with Renal Allograft Rejection

Background: CCL2 is a chemoattractant for monocytes/macrophages, T cells, and natural killer cells. It is shown to be involved in the immunological responses against renal allograft. This study was conducted to access the role of urinary CCL2 expression in predicting the rejection episodes in renal transplant patients.

Method: A total of 409 urine samples included in this study. The samples were consisted of (a) biopsy-proven graft rejection (n = 165); (b) non-rejection (n = 93); (c) non-biopsy stable-graft (n = 42), and (d) healthy renal donors (n = 109). The samples were quantified for the CCL2 using the MCP-1/CCL2 ELISA kit. The data were analyzed using the Statistical Package for Social Sciences (SPSS^®) and MedCalc^® statistical software.

Results: Results showed that the CCL2 levels were significantly increased in rejection group when compared with the non-rejection, stable-graft, and control, P < 0.05. The receiver operating curve’s characteristics illustrated that the urinary CCL2 level is a good predictor for graft rejection, with an area under the curve of 0.81 ± 0.03 with optimum sensitivity and specificity of 87% and 62%, respectively, at a cut-off value of 198 pg/mL. Kaplan–Meier curve also showed better cumulative rejection-free graft survival time in group with less than 198 pg/mL of CCL2 as compared to those with expression levels of more than 198 pg/mL (30 weeks vs. 3 weeks; log-rank test, P < 0.001).

Conclusion: In our study, noninvasive investigation of CCL2 levels in urine has showed potential to predict rejection episodes. It is suggested that the CCL2, with others markers, may help in early detection and monitoring of graft rejection episodes.     

Astilbin suppresses collagen-induced arthritis via the dysfunction of lymphocytes

Objective and Design: To examine the therapeutic effects of astilbin, a flavanoid isolated from Rhizoma Smilacis Glabrae, on arthritis and to compare it with cyclosporine A (CsA).Materials and Methods: Type II collagen-induced arthritis in mice and its in vitro assays for proliferation, matrix metalloproteinase (MMP) and NO production were performed.Results: Astilbin dose-dependently inhibited the footpad swelling, arthritic incidence, and clinical scores without influencing the body weights, while CsA showed strong inhibition with a significant weight loss. Histological examination revealed marked inflammatory damage in arthritic mice including joint swelling, synovial hyperplasia, and cartilage destruction. Against these, an intact joint structure was maintained in astilbin-treated or CsA-treated mice. In isolated spleen cells from arthritic mice, increased potentials in proliferation, NO production, and MMP-2 and 9 activities were suppressed dose-dependently by the oral administration of astilbin. Additionally, astilbin showed neither any cytotoxicity to nor influence on Con A-induced proliferation of spleen cells from naive mice, while CsA showed a dose-dependent cytotoxicity and inhibition of the proliferation.Conclusions: Astilbin may act as an efficient therapeutic agent for arthritis like CsA but with less toxicity. Its mechanism includes a selective suppression on lymphocyte functions via reducing MMP and NO production.Received 20 December 2002; returned for revision 4 February 2003; accepted by M. Katori 23 March 2003     

非HLA因素致大鼠肾移植CAN加快模型的建立

目的建立大鼠异体肾移植慢性移植肾肾病(CAN)加快模型,为研究非HLA免疫因素及非免疫因素致CAN的病因、病理及病理生理机制提供平台。方法采用雄性Fisher大鼠和Lewis大鼠分别作为供-受体,并以假手术组作为对照,进行异体原位肾移植。受体移植术前对供肾进行强化冷缺血处理1 h,于术后4 w,8 w,12 w分别观察各受体血肌酐和移植肾组织病理变化情况。结果移植术后4周Fisher-Lewis组开始出现血肌酐的升高及移植肾CAN的病理改变,8~12周病变渐趋明显,与对照组比较有统计学差异(P<0.05)。结论以Fisher和Lewis近交系大鼠作为供-受体建立的大鼠异体肾移植CAN加快模型是一种可靠、实用和研究价值高的肾移植实验动物模型。     

大鼠心脏移植排斥反应过程中外周血CD28、CD40通路相关分子的变化

目的探讨CD28、CD40共刺激通路与排斥反应的关系,同时也为排斥反应的诊断寻找一种新的检测指标。方法采用大鼠异位心脏移植模型,用免疫组化方法动态检测外周血单核细胞（PBMC）CD28、CTLA4、CD40及CD40L分子的表达。结果在0～4级排斥反应中,外周血细胞CD28分子阳性表达率在各组间的差异无统计学意义。外周血细胞表达CTLA4分子的阳性率随排斥反应增强而升高（P〈0.01）。CD40及CD40L在PBMC中的表达强度也随排斥反应的分级逐渐增强（P〈0.01）。结论外周血CTLA4、CD40及CD40L分子的表达与排斥反应有密切关系,动态检测这些分子有助于对排斥反应状态的评价。     

Value of a Simple Method to Assess Chronic Rejection in Renal Allograft on Electron Microscopy

Abstract

Electron microscopy is a powerful tool for the assessment of complex lesions in nontumor renal pathology, however it is a time-consuming procedure. We evaluated a simple method to assess morphological signs of chronic rejection in renal allograft that seems to have prognostic significance.