乙型肝炎病毒携带者肾移植术后应用他克莫司和环孢霉素A的临床研究

目的 比较他克莫司和环孢霉素A在乙型肝炎病毒携带者肾移植术后的疗效和安全性.方法 符合入选标准的109例肾移植患者,随机分成他克莫司(FK506)治疗组(52例)和环孢霉素A(CsA)治疗组(57例),随访2年,比较两组的人肾存活率、急性排斥反应(AR)发生率、肝功能异常发生率和药物转换率等.结果 CsA和FK506组的2年人肾存活率分别为86.0%/73.7%和94.2%/90.3%(P＜0.05).AR发生率分别为10.5%和9.6%(P＞0.05).CsA组和FK506组的肝功能异常发生率分别为26.3%和15.4%(P＜0.05).CsA组有21.1%的患者接受静脉护肝药物治疗,而FK506组为9.6%(P＜0.05).CsA组有14.4%的患者转换为FK506,而FK506组没有病人转成CsA(P＜0.05).转换后,谷丙转氨酶/谷草氨酶在10～50 d内由[(255.13±31.38/201.88±21.25)U/L)]降至[(31.25±11.50/25.13±9.68)U/L](P＜0.01).结论 对乙型肝炎病毒携带者肾移植患者,FK506比CsA有更好的疗效和更高的安全性,可作为首选的基础免疫抑制剂.     

NBD多肽预处理的树突状细胞延长移植心存活时间的实验研究

目的 探讨NBD多肽预处理的供体源性树突状细胞(DC)在诱导心脏移植免疫耐受中的作用及可能机制.方法 体外培养供体源性BALB/c小鼠骨髓树突状细胞并以NBD多肽预处理(NBD多肽-DC,在小鼠心脏移植前7 d,将NBD多肽.DC输至受者C57BL/6小鼠体内.应用Cu-T建立小鼠颈部异位心脏移植模型,观察心脏移植物存活时间,病理分析检测排斥反应程度.混合淋巴细胞反应(MLR)测定受者脾脏T细胞对供者同种抗原的反应性,并用ELISA方法测定受者血清Thl型细胞因子(IFN-γ和IL-12)和Th2型细胞因子(IL-4和IL-10)水平的变化.结果 NBD多肽-DC可使移植心脏存活天数延长至(21.83±3.54)d,较PBS对照组的(6.66±1.21)d明显延长(P＜0.01),降低排斥反应病理分级(Stanford 1～2级),能诱导受者脾脏T细胞的抗原特异性低反应性,使受者小鼠血清INF-γ和IL-12水平显著降低(P＜0.01).而IL-4和IL-10水平明显升高(P＜0.01).结论 NBD多肽预处理的供体源性DC能够诱导针对移植供者产生的特异性免疫耐受现象,其机制可能与诱导受者T细胞的抗原特异性低反应性及Th1/Th2免疫偏移有关.     

Dr Margaret Chan takes office as WHO Director-General

Background The aim of the current study was to investigate the role of interleukin （IL）-2, interferon （IFN）-y, IL-4 and IL-10 in a concordant hamster-to-rat cardiac xenotransplantation model. Methods A hamster-to-rat cardiac transplantation was performed using SD rats as recipients of Golden Syrian hamster hearts. A total of 60 SD rats were divided into four groups and treated as follows： control group （n=15）; splenectomy group （n=15）; CsA group （n=15）; CsA ＋ splenectomy group （n=-15）. Levels of IL-2, IFN-γ, IL-4 and IL-10 were measured by enzyme linked immunosorbent assay （ELISA）. Sera were harvested at different time points in each group： day 1, and 3 as well as the day the xenograft stopped beating in the control group and CsA group; day 1, 3, 7, 14 and 30 in the splenectomy group and CsA＋splenectomy group. The expression of P-selectin and intercellular adhesion molecule-1 （ICAM-1） was examined by immunohistochemical analysis of the xenogralt alter cardiac xenotransplantation. Results Serum levels of IL-2 and IFN-γ were upregulated in untreated （day 3） and splenectomy-treated animals （day 7） compared to CsA ＋ splenectomy treated animals （day 7）. IL-10 was upregulated in long-term survival recipients following splenectomy ＋ CsA. Neither P-selectin nor ICAM-1 expression was detected in long-term survival xenografts. Conclusions Serum IL-2 and IFN-γ were elevated following acute vascular rejection. Serum IL-10 was correlated to immunosuppression and protective effects in long-term survival rats following concordant cardiac xenotransplantation.     

洛伐他汀联合环孢素A对人外周血单个核细胞增殖、细胞因子表达及NK细胞毒作用的影响

目的 探讨洛伐他汀联合环孢素A（CsA)对体外培养的人淋巴细胞增殖、对某些细胞因子表达及NK细胞活性的影响。方法 Ficoll-Hypague密度梯度离心法提取人外周血单个核细胞（PBMC）;乳酸脱氢酶（LDH）释放试验测定细胞活性;^3H-标记甲基胸腺嘧啶（^3H-TdR)掺入法观察药物对细胞增殖及细胞毒作用的影响;ELISA-斑点法（ELISA-SPOT）检测细胞分泌的IL-2;放免法（RIA）测定细胞上清IFN-γ的浓度;半定量反转录-聚合酶链反应（RT-PCR）显示IL-2及IFN-γmRNA的表达。结果 洛伐他汀及CsA均可剂量依赖性地抑制体外培养的人淋巴细胞的增殖,IL-2和IFN-γ表达及NK细胞活性。两药联合使用具有协同作用。结论 他汀类药物可与CsA协同使用减缓移植排斥反应发生发展,延长移植物寿命。     

Effects of combined immune therapy on survival and Th1/Th2 cytokine balance in rat orthotopic liver transplantation

Background The induction of immune tolerance and suppression of allograft rejection has become the focus in the study of liver transplantation. The effect of immune therapy with anti-CD40L mAb alone or in combination with cyclosporine A (CsA) on the recipient survival and Th1/Th2 cytokine profile was studied to elucidate its immunological mechanism and role in rat orthotopic liver transplantation. Methods The model of rat orthotopic liver transplantation was established by modified Kamada’s technique. Recipients were divided into group A (control group): SD→SD; group B (group of rejection): SD→Wistar without any treatment; group C: SD→Wistar with CsA monotherapy from day 1 to day 5; and group D: SD→Wistar with CsA from day 1 to day 5 and anti-CD40L mAb on day 0 and day 2. The survival of the recipients in all groups was observed and ELISA technique was used to detect the level of cytokines in peripheral blood on post-transplant day 7. Results The survival period of recipients in groups A (>60 days) and D (>60 days) was significantly longer than that in group B (13.8±2.4 days). The serum levels of interleukin 2 (IL-2) and interferon γ in group B were significantly higher than those in other groups; the level of tumor necrosis factor α was higher but not statistically significant. In contrast, the serum levels of IL-4 and IL-10 in group D were elevated more significantly than those in group B (P<0.05). Conclusions Combined immune therapy can prolong the survival of allografts. Increased expression of Th2 cytokines, which is closely related to the induction of tolerance and suppression of rejection, is beneficial to the long-term survival of recipients and allografts.     

Safety of enteral rehabilitative therapy in rat small bowel transplantation

Objective To evaluate the safety of enteral rehabilitative therapy in rat small bowel transplantation.Methods Forty-eight rat recipients of allogeneic heterotopic small bowel transplantation (SD andWistar) were randomly divided into 4 groups according to the application or not of enteral rehabilitativetherapy and cyclosporine A (CsA). The pathological changes of the graft, IL-2 receptor expression inlamina propria lymphocytes, serum IL-2 concentrations, results of spleen lymphocytes transformationtest and the IL-2 secretion capacity were determined and compared.Results Enteral rehabilitative therapy could promote the immune function of the recipient so as toaugment the acute rejection. But such effects could be blocked by the commonly usedimmunosuppressant CsA. Under the imrnunosuppression of CsA (10 mg ~ kg1 ~ d1, i.m. ),application of enteral rehabilitative therapy diC not induce or aggravate acute rejection.Conclusion Under effective immunosuppression, application of enteral rehabilitative therapy is safein rat small bowel transplantation.     

Anti-CD25 monoclonal antibody modulates cytokine expression and prolongs allografts survival in rats cardiac transplantation

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<0.05 vs controls). Rats treated with simulect and CsA had the longest survival of 55.0±11.6 days (P<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.     

肾移植术后早期肝功能异常

目的　探讨肾移植术后 3个月内环孢菌素A(CsA)免疫抑制剂引起肝损害的治疗措施。方法　对19例肾移植术后出现肝功能异常的病例进行分析 ,测定肝功能异常时CsA谷值浓度 ;及时调整免疫抑制剂用量 ,配合保肝利胆治疗。结果　治疗 2～ 4周后 ,17例患者肝功能恢复正常 ;2例无效者 ,将CsA改为他克莫司 (FK5 0 6 )治疗 1个月后 ,肝功能指标逐渐恢复正常。结论　低剂量CsA、霉酚酸酯 (MMF)、泼尼松 (Pred)三联是目前较为理想的免疫抑制剂治疗方案 ,结合保肝利胆治疗 ,对减少术后早期CsA肝毒性的发生有一定疗效。     

肾移植受者BK病毒感染的临床诊断及治疗

目的 探讨肾移植受者BK病毒(BKV)感染的诊断及治疗方法.方法 选取肾移植术后48个月内的患者共227例.采集其血、尿样本,行BKV尿沉渣细胞学计数与实时荧光定量PCR检测病毒拷贝.对部分肾移植受者进行移植肾活检.将尿或血中BKV DNA阳性患者80例分成干预组(51例)与对照组(29例).干预组进行调整免疫抑制剂:19例环孢素A(CsA)减量,22例他克莫司(FK506)减量,10例FK506转换成CsA;对照组不进行干预,并且密切监测急性排斥反应.干预3个月后再次检测,比较组内和组间干预前后BKV活化指标的差异.结果 227例受者的尿decoy细胞、BK病毒尿症与病毒血症的阳性率分别为33.O%、33.5%和15.4%.干预组干预后尿decoy细胞、尿和血BKV数量的中位水平均为O,明显低于干预前(5.0个/10HP,1.50 x 104拷贝/ml,0拷贝/ml,均P<0.01).对照组观察前后尿decoy细胞、血BKV数量的中位水平差异无统计学意义(6.0个/10HPvs 5.0个/10HP、0拷贝/ml vs 0拷贝/ml,均P>0.05),尿BKV数量观察结束时上升(观察前:0.79×104拷贝/ml,观察后:2.21 x104拷贝/ml,P<0.01).上述各项指标干预前后的差值在干预组与对照组间差异均有统计学意义(均P<0.05).干预过程中所有患者均未出现急性排斥反应.确诊BKV相关性肾病4例,其干预治疗后尿decoy细胞计数以及血、尿BKV DNA均明显降低,移植肾功能有所恢复.结论 定量尿沉渣细胞学检测简单、易行、敏感,可以作为BKV活化的指标,间接反映肾脏病理情况.也可检测血、尿BKV DNA了解病毒活化情况、筛查BKV相关的移植肾肾病.减少免疫抑制剂剂量或换FKS06为CsA治疗肾移植术后BKV感染效果良好.     

肾移植术后长期应用环孢素2332例的临床远期随访?

目的：总结肾移植术后长期应用环孢素( CsA)的临床经验。方法分析接受首次肾移植、术后长期服用CsA 并维持随访的受者2332例。根据患者的年龄分为儿童组(<18岁)27例,成人组(18~60岁)2086例,高龄组(>60岁)219例,计算所有患者及分组的排斥反应发生率和1、3、5、10年人、肾存活率,并以成人组为对照,分别与儿童组、高龄组进行上述指标的比较。统计长期服用CsA不良反应的发生率。结果所有患者、儿童组、成人组以及高龄组急性排斥反应( AR)发生率分别为17．0%、40．7%、17．1%、13．2%,慢性排斥反应( CR)发生率相应为13．2%、29．6%、13．4%、9．1%;1、3、5、10年人、肾存活率分别为：所有患者97．0%/96．7%、93．2%/86．2%、88．4%/82．7%、83．4%/65．4%,儿童组96．3%/96．3%、92．6%/85．2%、88．9%/81．5%、81．5%/63．0%,成人组97．5%/96．9%、93．4%/86．1%、88．9%/82．8%、84．0%/65．3%以及高龄组94．5%/94．1%、91．8%/87．2%、83．6%/82．2%、78．1%/66．2%。儿童组AR、CR发生率高于成人组(P=0．003, P=0．022),但人/肾存活率与成人组比较差异无统计学意义(P=0．34, P=0．08)。高龄受者CR发生率低于成人组(P=0．035),生存率低于成人组(P=0．009),AR和移植肾存活率与成人组类似(P=0．074, P=0．28)。 CsA的不良反应有：肝功能损害(16．5%)、肾中毒(17．7%)、高脂血症(17．4%)、高血压(32．8%)、糖代谢异常(13．2%)、牙龈增生(35．7%)以及多毛(24．1%)等。通过减少 CsA剂量、免疫抑制剂联合用药、对症治疗等措施,多数患者症状消失或缓解。结论 CsA是一种安全、有效的免疫抑制剂,除可用于成人肾移植之外还可用于儿童及高龄受者。移植术前良好的HLA配型,CsA精准浓度调控以及联合用药有利于降低CsA剂量,从而减少CsA不良反应的发生。     

藏药结血蒿水提物的免疫抑制作用研究

目的研究结血蒿水提取物（AV-ext）对小鼠免疫反应的抑制作用。方法运用淋巴细胞增殖反应、混合淋巴细胞反应观察AV-ext体外应用和口服给药对小鼠脾细胞增殖的影响;运用小鼠脾细胞增殖试验,观察AV-ext体外应用对小鼠活化脾细胞分泌IL-2的影响;用明胶酶谱法和粘附分析法,观察AV-ext对小鼠活化T淋巴细胞移动和粘附能力的影响。结果AV-ext在1μg／mL-100μg／mL剂量范围内对脾细胞无明显的细胞毒性,但对刀豆蛋白A（ConA）诱导的小鼠脾细胞增殖反应、混合淋巴细胞反应具有明显的抑制作用,对小鼠活化脾细胞分泌IL-2、小鼠活化T淋巴细胞分泌基质金属蛋白酶9（MMP-9）及粘附能力有显著的抑制作用;连续7d每日口服给予150mg／kg和300mg／kg的AV-ext,能明显抑制小鼠脾细胞增殖及活化脾细胞分泌MMP-9。结论AV-ext能显著抑制小鼠的细胞免疫反应。     

ICOS-Ig combined with CsA induces long term survival of cardiac allografts in mouse

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.     

Growth hormone improves graft mucosal structure and recipient protein metaboli sm in rat small bowel transplantation

Objective To observe the effects of recombinant human growth hormone (rhGH) on graft structure and recipient protein metabolism in rat small bowel transplantation (SBT) and total parenteral nutrition (TPN) models. Methods Twenty recipients of rat allogeneic heterotopic small bowel transplants (SD→Wistar) were divided into two groups (GH group and control group).Both groups were supported by standard TPN.Acute rejection was suppressed with CsA 10 mg·kg-1·d-1 intramuscularly.All rats in the experimental group received subcutaneous rhGH 1 U·kg(-1)·d(-1) after transplantation.Morphological mucosal indices of transplanted gut and metabolic parameters such as body weight, nitrogen balance, urinary 3-methyl histidine excretion and serum albumin of the recipients were compared between two groups. Results The application of rhGH promoted graft recovery significantly compared with standard TPN support alone.On postoperative day 14, all morphological indexes of transplanted gut recovered to the preoperative state.Protein metabolism in the recipient was also significantly improved.rhGH decreased the catabolism of protein, accelerated regaining of positive nitrogen balance and corrected hypoalbuminemia. Conclusion GH is an effective metabolic intervention in SBT.It may promote the structural repair of the graft and correct the metabolic disturbance.It is useful in improving the outcome of clinical SBT.     

局部注射环孢素A对非肥胖糖尿病小鼠下颌下腺分泌功能及炎症的影响

目的: 探讨非肥胖糖尿病(non-obese diabetic, NOD)小鼠下颌下腺局部注射环孢素A(cyclosporine A, CsA)对腺体唾液分泌功能及炎症的影响。方法: 选用21只14周龄和18只21周龄雌性NOD小鼠,随机平均分为低剂量组、高剂量组和对照组。NOD小鼠下颌下腺局部注射CsA 1周后,检测刺激性唾液流率;取下颌下腺标本,制作石蜡切片,用苏木精-伊红(hematoxylin-eosin staining, HE)染色,显微镜下观察腺体淋巴细胞浸润程度;用徕卡图像分析系统计数淋巴细胞浸润灶的数量,计算灶性指数和淋巴细胞浸润灶的面积比;用实时荧光定量聚合酶链式反应(quantitative real-time polymerase chain reaction, qRT-PCR)检测下颌下腺中肿瘤坏死因子-α(tumor necrosis factor-α, TNF-α)、干扰素-γ(interferon-γ, IFN-γ)、白介素-4(interleukin-4, IL-4)、IL-13、IL-17F、IL22和IL-23a等炎症细胞因子的表达;用脱氧核糖核苷酸末端转移酶介导的缺口末端标记法(terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling, TUNEL)检测下颌下腺凋亡细胞;用全自动生化分析仪测量血清肌酐(serum creatinine,Scr)、尿素氮(blood urea nitrogen, BUN)、尿酸(uric acid, UA)、丙 氨 酸 氨 基 转 移 酶(alanine aminotransferase,ALT)、天冬氨酸氨基转移酶(aspartate aminotransferase,AST)、碱性磷酸酶(alkaline phosphatase, ALP)、白蛋白(albumin, ALB)和γ-谷氨酰基转移酶(γ-glutamyl transferase,GGT), 评估肝肾功能。结果: 下颌下腺局部注射CsA后,14周龄和21周龄NOD小鼠的刺激性唾液流率较同龄对照组明显增加(P<0.01或P<0.05);14周龄低剂量组NOD小鼠下颌下腺淋巴细胞浸润灶的灶性指数和面积比较同龄对照组显著减少(P<0.01);低剂量和高剂量组减轻炎症反应和改善唾液分泌功能的作用相似;下颌下腺整体炎症细胞因子表达水平无明显降低;低剂量和高剂量组下颌下腺凋亡细胞数和对照组相比有减少趋势,但差异无统计学意义;局部注射CsA对NOD小鼠肝肾功能无影响。结论: 局部应用CsA可减轻NOD小鼠的下颌下腺淋巴细胞浸润,并改善唾液分泌功能。     

环孢素A对正常人早孕滋养层细胞IL-10和IFN-γ分泌的影响

目的探讨环孢素A(CsA)在体外对早孕期滋养细胞产生白细胞介素10(IL-10)和干扰素Y(IFN-γ)的影响。方法采用酶消化法分离绒毛滋养细胞，加入不同浓度的CsA进行体外培养。计算机图像分析系统及半定量逆转录-聚合酶链反应(RT—PCR)检测滋养细胞上IL-10和IFN-γ蛋白及mRNA的表达。结果CsA在0．1umol／L、1umol／L时较对照组对滋养细胞的IL-10的蛋白分泌和mRNA表达均有明显促进作用(P＜0．05)；不同浓度的CsA对IFN-γ蛋白分泌和mRNA表达均无明显作用(P＞0．05)。结论CsA在合适浓度范围内对滋养细胞的IL-10、IFN-γ分泌有良性调控作用。     

应用树突状细胞单克隆抗体预防脾移植排斥反应的实验研究

目的 建立治疗性单克隆抗体溶液持续器官灌注模型，应用抗大鼠树突状细胞单克隆抗体（WZD）降低大鼠移植脾的免疫原性。方法 以WZD溶液持续灌注移植脾，筛选最佳方案。并观察灌注后沸合淋巴细胞培养（mixed lymphocye culture,MLC）中淋巴细胞的增殖情况及脾的超微结构。结果 WZD灌注组MLC淋巴细胞增殖能力明显降低，与对照组及应用环孢霉素A（Cyclosporin A,CsA）组相比差异显著（P＜0.05），与WZD灌注＋CsA组相比无明显差异（P＞0.05），21℃灌注组移植脾细胞功能活跃，线粒体损伤小。结论 移植脾在21℃下，每小时给予灌注50ml单抗溶液获得了最佳效果，WZD溶液灌注移植脾，可去除树突状细胞，确能降低其免疫原性，有可能减少免疫抑制剂的应用剂量。     

环孢素A血药浓度C0与C2的线性相关性分析对肾移植受者早期临床预后的预示作用

目的 探讨环孢素A(CsA)药代动力学参数的个体内变异度对肾脏移植受者移植后早期临床预后的影响.方法 以移植后早期接受CsA、吗替麦考酚酯(MMF)、皮质激素三联免疫抑制治疗的44例同种异体肾脏移植受者作为研究对象,采用酶增强免疫法(EMIT)法测定CsA和MMF的活性成分霉酚酸(MPA)的血药浓度,包括用药前谷值(C0)和用药后2h峰值(C2),分析CsA C0与CsA C2的线性相关性并依此分组(相关组和非相关组),比较两组移植术后早期各项临床事件(感染、急性排斥、急性排斥和感染合并、移植肾失功和CsA肝、肾毒性反应等)的发生率和MPA血药浓度-时间曲线下面积(AUCMPA)的达标率.结果 44例患者中,CsA C0与CsA C2呈非线性相关者31例(70.45％),呈线性相关者13例(29.55％).统计学分析结果显示:相关组与非相关组移植后第2～4周临床事件的总体发生率、急性排斥事件的发生率和AUCMPA的达标率比较,差异均有统计学意义(P≤0.05).结论 CsA药代动力学参数C0与C2的线性相关性对肾脏移植受者移植后早期的临床预后有预示作用.     

致敏受者细胞因子基因多态性与肾移植急性排斥反应的关系

OBJECTIVE: To investigate the relationship between cytokine gene polymorphism in sensitized kidney transplant recipients and acute rejection episodes. METHODS: PCR using sequence-specific primer (PCR-SSP) was performed to determine the cytokine genotypes of tumor necrosis factor-alpha (TNF-alpha), interleukin-10 (IL-10), transforming growth factor-beta1 (TGF-beta1), interleukin-6 (IL-6), interferon-gamma (IFN-gamma) in 97 sensitized kidney transplant recipients. The association of cytokine genotypes with early graft rejection was explored. RESULTS: Acute rejection occurred in 23 of the 97 patients during the first three months after operation. The incidence of acute rejection was higher in the recipients with high TNF-alpha or high IL-10 producer genotype (51.9% and 55.5% respectively) than in the recipients with low TNF-alpha or low to intermediate IL-10 producer genotype (12.9% and 13.3% respectively, P<0.01). The incidence of acute rejection was even higher in the recipients with high TNF-alpha in combination with intermediate to high IL-10 producer genotype than in the recipients with low TNF-alpha combined with low IL-10 producer genotype (62.5% vs 8.5%, P相似文献   

白细胞介素15和骨桥蛋白在大鼠肾移植急性排斥反应早期的表达

目的 研究白细胞介素(IL)15、骨桥蛋白、穿孔素及颗粒酶B在大鼠肾脏移植急性排斥反应(AR)早期的表达变化.方法 以BN大鼠和LEW大鼠分别作为供受体,建立大鼠肾移植动物模型.环孢素A处理组(CsA组):(BN→LEW,术后注射环孢素A);IL-15阻断组:(BN→LEW,术后注射IL-15抗体);AR组:(BN→LEW,术后注射生理盐水);对照组:(LEW→LEW,术后注射生理盐水).对照组6只大鼠,其余组10只大鼠,于移植后1、3、5、7 d取外周血,逆转录一聚合酶链反应(RT-PCR)动态检测骨桥蛋白、IL-15、穿孔素及颗粒酶B mRNA的表达,并作移植肾病理分析.结果 AR组、CsA组及IL-15阻断组肾移植术后IL-15、骨桥蛋白mRNA表达逐渐上调,第5天均达到高峰;对照组均处于低水平.术后第5天,CsA组和IL-15阻断组IL-15 mRNA分别为9685±1440、4346±741均低于AR组(17 022±2153,P<0.01),IL-15阻断组明显低于CsA组(P<0.01);CsA组和IL-15阻断组骨桥蛋白mRNA分别为13 226±1565、19 112±2908均低于AR组(24 663±2449,P<0.01),IL-15阻断组明显高于CsA组(P<0.01).术后第5天IL-15阻断组和CsA组穿孔素和颗粒酶B mRNA表达明显低于AR组(P<0.01).移植肾病理组织检查显示,AR组呈现重度急性排斥反应,IL-15阻断组排斥反应征象轻微.结论 大鼠肾移植AR发生早期骨桥蛋白、IL-15、穿孔素和颗粒酶B mRNA在外周血中均高水平表达,通过阻断IL-15/IL-15受体途径可明显下调颗粒酶B和穿孔素mRNA的表达.     

CD28、CD40通路共刺激对淋巴细胞增殖反应的影响及CsA的抑制作用

目的：探讨CD28、CD40通路共刺激后淋巴细胞增殖反应的变化及免疫抑制剂环孢素A(CsA)、抗CTLA4单克隆抗体对共刺激通路激活后淋巴细胞增殖反应的影响。方法：采用单克隆抗体与淋巴细胞表面CD3、CD28及CD40L分子结合产生相应刺激信号,根据刺激条件不同设组为：①抗CD3单抗单刺激(A组)(剂量为10μg／L、100μg／L、1000μg,／L);②抗CD3单抗 抗CD28单抗(B组);③抗CD3单抗 抗CD40L单抗(C组);④抗CD3单抗 抗CTLA4单抗(D组)共刺激(A、B、C、D组中抗CD3单抗剂量固定为100μg／L,其余3种单抗各设10μg／L、100μg／L、1000μg／L3种剂量);⑤抗CD3单抗 抗CD28单抗 抗CD40L单抗(E组);⑥抗CD3单抗 抗CD28单抗 抗CTLA4单抗(F组)共刺激(E、F组中抗CD3单抗和抗CD28单抗的剂量固定为100μg／L,抗CD40L单抗和抗CTLA4单抗的剂量各设10μg／L、100μg／L、1000μg／L);⑦CsA干预组：抗CD3单抗 CsA(G组);⑧抗CD3单抗 抗CD28单抗 CsA(H组);⑨抗CD3单抗 抗CD28单抗 抗CD40L单抗 CsA(I组),G、H、I组中所有单抗浓度均固定为100μg／L,CsA浓度设为10μg／L、100μg／L、1000μg／L。采用[^3H]-TdR同位素掺人法测定淋巴细胞增殖水平,液体闪烁计数仪测定放射性计数值。结果：用抗CD3单抗 抗CD28单抗共刺激后,淋巴细胞增殖反应明显高于抗CD3单刺激,而在抗CD3单抗 抗CD40L单抗刺激组,淋巴细胞增殖反应低于抗CD3单刺激组。抗CTLA4单抗所提供的刺激信号可抑制抗CD3单刺激及抗CD3 抗CD28共刺激导致的淋巴细胞增殖反应,并且随着抗CTLA4单抗剂量的增加,抑制作用增强。CsA对共刺激后的淋巴细胞增殖反应有抑制作用,且随着剂量增大其抑制作用也增强,但对单刺激后增殖反应的抑制作用更为明显。结论：CD28共刺激通路在淋巴细胞活化中起着关键作用。抗CD40L单抗的刺激作用可能被其对T细胞与抗原递呈细胞(APC,包括B细胞等)间的阻断效应所掩盖。抗CTLA4单抗及CsA对共刺激后淋巴细胞的增殖反应均有抑制作用。