PRA配型技术在致敏受者肾移植术中的应用研究

目的 探讨群体反应性抗体(PRA)配型技术在致敏受者肾移植中的临床效果.方法 应用抗原板(LAT),采用酶联免疫吸附法(ELISA)检测肾移植受者术前的PRA;采用PRA配型技术进行术前配型.结果 12例致敏受者组采用PRA配型技术,肾移植术后肾功能恢复正常,无1例发生超急性排斥反应,术后1个月内急性排斥反应的发生率为25%;同期43例非致敏受者组,术后1个月内急性排斥反应的发生率为18.6%,虽较致敏受者组低,但两组之间差异无统计学意义.结论 PRA配型技术对减少致敏受者肾移植排斥反应,提高移植物存活率具有重要意义.     

PRA配型技术在肾移植中的应用研究

目的探讨群体反应性抗体 (PRA)配型新技术对肾移植近远期的效果。方法 85 4例患者肾移植前运用PRA新技术进行组织配型 ,并行血浆置换 ,未采用PRA组织配型的 42 3例作为对照 ,观察肾移植术后免疫指标变化、近期 (AR)发生率以及对长期存活的影响。结果未采用PRA组织配型组发生超急性排斥反应 (HR) 9例 (2 1% )、急性排斥反应 198例 (47% ) ;1年人/肾存活率 86 7% /76 3%、3年人 /肾存活率 72 5 % /6 7 9%、5年人 /肾存活率 6 9 5 % /4 9 3%。采用PRA配型新技术共 85 4例 ,肾移植术后未发生超急性排斥反应 ,发生急性排斥反应 16 2例 (19 0 % ) ,1年人肾存活率达 97 3% /95 0 %、3年人肾存活率 92 0 % /84 2 %、5年人 /肾存活率 87 0 % /81 6 %。结论PRA阴性配型可杜绝超急性排斥反应发生 ,降低急性排斥反应发生率 ,提高人 /肾长期存活率。     

群体反应性抗体技术及HLA配型在1700例肾移植中的应用研究

OBJECTIVE: To evaluate the role of panel reactive antibody (PRA) screening and human leukocyte antigen (HLA) typing in renal transplantation. METHODS: PRA screening and HLA typing were performed in 1 700 patients eligible for the first group of renal transplantation who had 3 to 6 HLA matches in HLA-A, B and DR with the donor, and in cases positive for PRA, plasma exchange was conducted. Another 423 patients who did not receive PRA screening or HLA typing constituted the second group. The changes of immune variables, incidences of acute rejection and the effect of HLA-A, B, DR matching on long-term graft survival were observed. RESULTS: In 1 700 cases of group 1, post-transplantation CsA dose was reduced to 5 to 7 mg*kg(-1)*d(-1) and the graft function recovery time ranged from 2 to 16 d, averaging 5 d. Acute graft rejection occurred in 252 (14.8%) cases, but no hyper-acute rejection was observed. The 1-, 3- and 5-year patient/graft survival rates were 98.6%/96.7%, 93.1%/87.3% and 88.1%/83.6% respectively. In group 2, CsA dose ranged from 8 to 12 mg*kg(-1)*d(-1) and the graft function recovery time was 4 to 30 d, averaging 13 d. Hyper-acute rejection occurred in 9 (2.1%) and acute rejection in 198 (46.8%) cases, and the 1-, 3- and 5-year patient/graft survival rates were 86.7%/76.3%, 72.5%/67.9% and 69.5%/59.3% respectively. CONCLUSIONS: Negative PRA and good HLA matching can eliminate the incidences of hyper-acute rejection, decrease the rate of acute rejection and improve both patient and graft survival rates.     

3 102例次尸体肾移植临床分析

目的 对3 102例次尸体肾移植进行临床分析.方法回顾性分析1978年1月～2007年1月3 102例次肾移植受者存活率、主要并发症以及死亡因素,并应用Cox模型对组织配型、免疫抑制剂方案、排斥,再次肾移植等影响因素进行多因素分析.结果 (1)应用钙调神经素抑制剂前、后1、3、5、10年人/肾存活率(%)为65.6/65.6 vs 95.1/94.8, 48.3/48.3 vs 88.4/85.4, 30.1/30.1 vs 78.0/73.2和11.8/11.8vs 66.0/60.6;(2)超急性排斥发生率1997年前后分别为23/1 120 vs 1/1 897;急性排斥反应19.5%,慢性移植物肾病18.9%;(3)多因素分析结果表明,肾功延迟恢复、高龄受者、配型、免疫药物方案、急性排斥、外科并发症等因素可对移植肾的长期存活产生重要影响;(4)肾移植受者死亡的主要原因依次为:心脑血管系统疾病(51.4%),肝功能衰竭(23.1%),严重感染(12.9%),消化道出血(6.9%);(5)HLA供、受者配型、淋巴细胞毒和PRA可明显减少超急性排斥反应,有利于移植肾长期存活.结论尸体肾移植是救治晚期肾功能衰竭患者的有效方法.     

肾移植患者围手术期群体反应性抗体检测的临床意义

目的:研究肾移植患者围手术期群体反应性抗体(PRA)的水平与移植肾急性排斥的关系。方法:采用ELISA-PRA检测法,对34例尸体肾移植患者进行手术前、术后1周、术后2周、术后1个月血清PRA检测,并分析其结果与肾移植急性排斥的关系。结果:34例患者中,移植前PRA阳性者(PRA)>10％)9例(26.5％),有5例PRA>50％(51％～80％),术前行血浆置换。PRA阴性者25例(73.5％)。PRA阳性组中,有5例发生急性排异,其中2例切除移植肾恢复血液透析。PRA阴性组中,有4例发生急性排异,治疗后肾功能恢复正常。两组相比排异发生率有统计学差异(P<0.05)。术后PRA阳性者11例(术前PRA阴性转阳者2例),发生排异6例(1例为术前PRA阴性)。术后PRA阴性者中,有3例发生排异。两组相比排异发生率有统计学差异(P<0.05)。结论:①患者肾移植术前体内PRA水平对移植肾排异有显著影响;②患者肾移植术后体内PRA水平影响移植肾急性排异的发生和转归。     

小剂量静脉滴注人免疫球蛋白在群体反应抗体阳性肾移植患者中的临床应用分析

目的  探讨群体反应抗体（PRA）阳性肾移植受者应用小剂量人免疫球蛋白（IVIG）后,PRA的下降程度以及移植肾功能的恢复效果。方法  ①观察组：A组术前高PRA肾移植患者4例;B组术后出现移植肾功能延迟恢复,监测出PRA升高患者7例;C组术后远期出现血肌酐升高,监测PRA升高同时病理穿刺证实为体液性排斥反应患者8例;②对照组：回顾性、随机挑选既往与A、B、C组同样表现的患者。治疗方案：A、B组血浆置换（PP）联合小剂量IVIG持续静脉滴注0.1 g/（kg·d）;C组内固醇激素冲击联合小剂量IVIG持续静脉滴注0.1 g/（kg·d）;对照组治疗方案中无IVIG的应用。比较观察组与对照组PRA下降程度和患者的预后。结果  经系统性、阶段性治疗后,A、B、C组中PRA均有不同程度降低,与对照组比较,A组肾移植术后排斥反应发生几率、B组移植肾功能恢复时间、C组移植肾血肌酐下降程度高于对照组,差异有统计学意义。结论  与传统大剂量IVIG比较,小剂量IVIG也能有效降低肾移植受者PRA水平,其对高PRA水平患者的治疗具有积极意义,且大大降低医疗成本。

     

Simulect 和 Zenapax 应用于肾移植诱导治疗的5年临床观察

目的评价2剂Simulect和5剂Zenapax在肾移植中诱导治疗预防急性排斥反应(AR)的有效性、安全性以及对近、远期人/肾存活的影响。方法选择1999年4月~2001年4月首次肾移植患者102例,分成Simulect组(54例)和Zenapax组(48例),在三联免疫抑制剂基础上(环孢素A/FK506、骁悉、皮质激素)加用Simulect(术前2h和术后第4天分别予20mg静滴)或Zenapax(1mg.kg-1.d-1,最大剂量100mg,首剂术前2h,此后每2周1剂,共5剂)。观察术后3个月内肾功、AR、移植肾功能延迟恢复(DGF)、急性肾小管坏死情况;术后5年内肾功、排斥反应、并发症及人/肾存活情况。结果术后3个月内AR发生率明显降低(Simulect组:14.8%;Zenapax组:14.6%);首次AR发生时间延迟;激素治疗对大部分AR有效;5年内再次排斥反应发生率为9.3%(Simulect组)和6.3%(Zenapax组)。术后肾功能恢复明显加快,早期及远期肾功能良好。未出现细胞因子释放综合征,仅2例DGF。5年内,感染、糖尿病、高脂血症、恶性肿瘤等未见增加。5年人/肾存活良好,均达95%以上。结论2剂Simulect和5剂Zenapax预防肾移植术后AR的效果好、安全性高,有利于早期肾功能恢复和远期人/肾存活。     

活体肾移植术对供受者的影响

目的 评价活体肾移植术对供受者健康的影响。方法 对6组活体肾移植术供受者进行随访,动态观察供受者术后并发症及肾功能情况。结果 6名供者,肾切除术后无并发症,术后肾功能正常。6名受者,其中1名PRAl00％,但患者和家属坚决要求手术,尸体肾移植术失败后再行活体肾移植术后发生超排,维持性透析状态。5名均予三联免疫抑制治疗,术后无其他不良并发症,肾功能均恢复至正常范围,其中1名术后发生急性排异,予甲基强的松龙(MP)冲击及抗淋巴细胞球蛋白(ATG)治疗后肾功能恢复正常,另1名发生临界排异,予MP冲击5天缓解。结论 活体肾移植术效果肯定,可延长受者及移植物存活时间,对供者健康影响较小,可以在有一定条件的单位开展,并应重视对供受双方的术前健康评价和术后随访。     

术前单次大剂量ATG诱导治疗在PRA阳性肾移植受者中的应用

目的评价术前单次大剂量兔抗胸腺细胞球蛋白（ATG）诱导治疗用于群体反应性抗体（PRA）阳性肾移植受者时的有效性及安全性。方法26例PRA阳性肾移植受者组成PRA阳性组（PRA≥10％）,该组患者于肾移植手术之前2h开始接受单次大剂量ATG诱导治疗（Fresenius,9mg／kg）。另外选取同时期接受肾移植手术的PRA阴性受者组成阴性对照组（PRA〈10％,n=30）,该组患者仅于术前6h口服骁悉1g作为诱导治疗。两组患者的维持免疫抑制剂方案均采用标准的三联方案（钙调蛋白抑制剂＋骁悉＋强的松）。两组患者术后均接受12个月的随访,对排异反应事件、感染事件和肾功能变化进行记录。结果在术后12个月中,PRA阳性组有4例患者（15．4％）出现急性排异发应（AR）,阴性对照组内有6例患者（20．0％）出现AR（P=0．737）。PRA阳性组内6例患者（23．1％）共发生10次感染事件（1．7次／例）,阴性对照组内有8例患者（26．7％）共发生11次感染事件（1．4次／例）（P=0．757和P=0．890）。PRA阳性组内的患者接受术前单次大剂量ATG诱导治疗后未出现严重的副作用,与对照组比较差异无统计学意义。PRA阳性组和对照组患者的平均住院时间分别为（16．2±3．1）d和（16．7±3．3）d（P=0．563）。两组患者均未发生移植物功能延迟恢复（DGF）。两组患者的1年人肾存活率均为100％。结论术前单次大剂量ATG诱导治疗安全有效,可以明显降低PRA阳性患者的AR和DGF的发生率,改善移植肾的预后。     

肾移植群体反应性抗体检测641例分析

目的探讨群体反应性抗体检测(PRA)对于肾移植的意义。方法采用ELISA方法对641例肾移植患者进行PRA检测:术前570例、术后71例。结果570例术前检测PRA,阴性490例,术后发生急性排斥反应35例;弱阳性68例,术后发生急性排斥反应36例;12例阳性术后检测仍为阳性,发生急性排斥反应10例。71例术后检测PRA,阴性59例,发生急性排斥反应3例;阳性12例,发生急性排斥反应7例。结论肾移植患者术前检测PRA有助于减少排斥反应的发生。     

MICA抗体监测在肾移植术后急、慢性排斥反应中的意义

目的探讨肾移植受者的抗MICA抗体水平与急性和慢性排斥反应的相关性及其对移植肾功能的影响。方法采用酶联
免疫吸附方法检测接受同种异体肾移植手术的患者血清中MICA 抗体,并同步检测HLA抗体、肾功血肌酐、尿量及移植肾超声
等临床指标。本研究分两部分分别监测在肾移植术后急、慢性排斥反应中MICA抗体的变化。结果第一部分41例研究对象
中有18例发生急性排斥反应,该组中MICA抗体阳性率高于肾功能稳定组（P<0.05）;MICA抗体阳性组的急性排斥反应发生率
高于MICA抗体阴性组（P<0.05）;术后MICA抗体动态监测时发现,MICA抗体水平逐渐升高2~3 d后出现排斥反应,给予抗排
斥治疗后血肌酐水平逐渐降至正常,MICA抗体水平亦逐渐下降,但仍维持在阳性范围。第二部分40例患者中21例患者出现
慢性排斥反应,其中MICA抗体阳性率明显高于肾功稳定组患者（P<0.05）。慢排组中MICA抗体阳性患者的血肌酐与阴性组
的血肌酐水平比较有统计学差异（P<0.05）。移植肾穿刺病理结果显示MICA抗体阳性患者C4d沉积均为阳性。结论MICA
抗体可预测急性排斥反应的发生及治疗效果,对于及时诊断及治疗排斥反应提供了一个重要指标,同时也是导致慢性排斥的主
要因素之一,可影响移植肾的长期存活。
     

Factors affecting the long-term renal allograft survival

Background  In the past decades, the one-year graft survival of cadaveric renal allografts has been markedly improved, but their long-term survival has not kept pace. The attrition rate of renal allografts surviving after one year remains almost unchanged. The causes for late graft loss are multiple. The aim of this study was to analyze the predictive factors that impact long-term survival of grafts after kidney transplantation.

Methods  We retrospectively analyzed 524 kidney transplantation patients who were treated in our hospital between January 1991 and January 2000, including 254 patients who had lived more than 10 years with normal graft function (long survival group), and 270 cases whose renal graft had survived less than 10 years (control group). Specifically, we analyzed 10 factors that may potentially affect graft survival by both univariate and Logistic model multivariate analyses to pinpoint the independent risk factors. 

Results  Univariate analyses showed that no significant differences existed in the age or gender of recipients, dialysis time, lymphotoxin levels, or cold ischemia time between the two groups. However, the ratio of delayed graft function and acute rejection, and the uric acid levels of patients in the long survival group were significantly lower than those in the control group (P <0.01). Furthermore, we found that the concentration of cyclosporin A at one year after transplantation and the histocompatibility antigen match of donor-recipients for patients within the long survival group were significantly higher than those in the control group (P <0.01). Furthermore, multivariate analyses showed that these four factors were independent risk factors that impact patient survival.

Conclusions  The ratios of delayed graft function and acute rejection, the concentration of cyclosporin A at one year after transplantation, and serum uric acid levels are very important factors that affect the long-term survival of renal grafts.

     

肾移植2 200例次临床分析

目的 总结1908例（2200例次）肾移植手术的临床经验,提高肾移植术后人、肾存活率。方法 总结1985年以后人、肾1年、3年、5年的存活率;肾移植主要并发症及其处理原则;影响患者再移植存活率的因素;HLA－抗原／基因配型及群体反应抗体（PRA）检测。结果 （1）自1985年临床使用环孢素A（CSA）后,其1年人、肾存活率为87.3％,3年人、肾存活率为80.2%,5年人、肾存活率为67.0%.(2)50岁以上肾移植患者302例,术后1年移植肾存活率8.4%(252/302),1年人存活率8534%(258/302).(3)肾移植术后患者死亡原因主要是心血管系统疾病及感染。心血管系统疾病占死亡原因的50.7%,感染占死亡率的13.5％（4）。肾移植术后恶性肿瘤 的发病率为1.5％（23／1580）。（5）肝损害患者有独特的药代动力学特点。（6）良好的HLA供－受者配型可以减少肾移植术后急性排斥反应的发生率,有利于移植肾的长期存活。在HLA抗原不配合的情况下,受者应尽量选择不具有免疫原性抗原／基因的供肾移植。（8）对于慢性排斥应应采取综合方法进行治疗。结论 良好的组织配型、肾移植术后免疫抑制药物的合理应用、对移植术后并发症的预防及及时治疗是提高肾移植术后人、肾存活率的重要因素。     

群体反应性抗体对肾移植后人/肾存活率影响的临床分析

目的回顾性调查群体反应性抗体(PRA)对肾移植术后1、3、5年人/肾存活率的影响。方法纳入北京军区第二八一医院2000年1月~2012年3月肾移植受者469例,采用酶联免疫吸附法(ELISA)检测受者移植前PRA水平,以PRA≤10%为阴性结果,10%40%为高度致敏,并对1、3、5年人/肾存活率进行统计。结果 469例肾移植受者中,PRA阴性349例(阴性组),PRA阳性120例(阳性组),其中Ⅰ类抗体阳性66例,Ⅱ类抗体阳性31例,23例同时存在Ⅰ类和Ⅱ类抗体。术前PRA阴性组与阳性组1、3、5年人存活率分别为98.3%、90.9%、80.7%和93.3%、82.9%、62.9%;1、3、5年肾存活率分别为96.8%、87.9%、75.9%和86.7%、76.1%、50.5%,二组相比1、3、5年人/肾存活率均差异有统计学意义(P<0.05),轻度致敏组的1、3、5年人存活率、肾存活率与PRA阴性组相比,差异无统计学意义(P>0.05);中度致敏组的1、3、5年人/肾存活率与阴性组比较,差异有统计学意义(P<0.05);高度致敏组的1、3、5年人/肾存活率与阴性组比较,差异有统计学意义(P<0.05)。结论 PRA是肾脏移植术前筛选致敏受者的重要指标,PRA阳性会影响移植物的长期存活,PRA阳性患者在肾移植手术前必须进行严格的组织配型,采取措施降低抗体水平,选择合适的供体与手术时机,以提高人/肾存活率。     

Expression characteristics of major histocompatibility complex class I-related chain A antibodies and immunoadsorption effect in sensitized recipients of kidney transplantation

Background  Sensitized recipients have a high risk of immunological graft loss due to hyperacute rejection and/or accelerated acute rejection. The presence of major histocompatibility complex class I-related chain A (MICA) antibodies has also been described associated with an increased rate of kidney-allograft rejection. The aim of this study was to describe the expression of MICA antibodies in sensitized recipients of renal transplantation and evaluate its influence on the kidney transplantation recipients.

Methods  A total of 29 sensitized recipients were included in this study. All patients received the MICA antibodies detection before and after protein A immunoadsorption. Panel reactive antibody (PRA), HLA-matches, acute rejection and postoperative one to four-week serum creatinine level were also collected and analyzed, respectively. No prisoners were used in this study.

Results  Eight patients (27.6%) in all 29 sensitized recipients expressed the MICA antibodies but did not show higher acute rejection rate than the non-expressed patients (3/8, 37.5% vs. 8/21, 38.1%; P=1.000). Recipients with PRA >40% showed higher expression levels of MICA antibodies than the recipients with PRA <40% (7/16, 43.8% vs. 1/13, 8.3%; P=0.044). HLA mismatch did not have any effect on the expression of MICA antibodies (P=1.000). MICA antibodies positive group had higher serum creatinine level than the control in postoperative one week ((135.4±21.4) µmol/L vs. (108.6±31.6) µmol/L, P=0.036), but no significant difference in postoperative four weeks ((89.0±17.1) µmol/L vs. (77.1±15.9) µmol/L, P=0.089). MICA antibodies decreased significantly after protein A immunoadsorption.

Conclusions  MICA antibodies increase in the sensitized recipients, which have significant effects on the function of allograft in early postoperative period. Protein A immunoadsorption can decrease MICA antibodies effectively in sensitized recipients.

     

TWO-YEAR OBSERVATION OF A RANDOMIZED TRIAL ON TACROLIMUS-BASED THERAPY WITH WITHDRAWAL OF STEROIDS OR MYCOPHENOLATE MOFETIL AFTER RENAL TRANSPLANTATION

Objective To evaluate the safety and feasibility of steroid or mycophenolate mofetil （MMF） withdrawal from tacrolimus-based immunosuppressant regimen in renal allograft recipients.
Methods A cohort of 45 patients following cadaveric renal allograft transplantation were randomly divided into 3 groups based on the regimen of combination of tacrolimus, steroid, and MMF： triple therapy group, steroid withdrawal group, and MMF withdrawal group. During 2 years, survival of patients and allografts, clinical acute rejection, adverse events, hepatic and renal allograft function, and blood lipids were monitored to evaluate the safety and feasibility of steroid or MMF withdrawal after renal transplantation.
Results During two-year observation, steroid or MMF was successfully withdrawn from immunosuppressant regimen based on tacrolimus without any clinical acute rejection renal allografts kept excellent function. Some adverse events among groups. Patient and graft survival rates were 100% and all the occurred and there were no significant differences
Conclusion Withdrawal of steroid or MMF in low-immunological-risk renal allografts treated with tacrolimus-based immunosuppressant regimen can be achieved with no increased risk of acute rejection.     

良好的HLA配型可改善PRA高敏受者的移植效果

报告5例淋巴细胞群体反应抗体（PRA）为48％～76％，采用理想的HLA配型，供受者间HLA－A、B、DR位点在3～5个抗原相合情况下进行移植，术后3例发生急性排斥反应，经用甲基强的松龙及OKT3冲击治疗后排斥逆转。5例全部成功，术后均获得随访，人／肾存活9个月～2年4例，3年半1例。讨论了PRA高敏感对移植物的影响，良好的HLA配型对移植效果的影响。     

Impact of human leukocyte antigen matching and recipients′ panel reactive antibodies on two-year outcome in presensitized renal allograft recipients

Background Renal transplantation in sensitized candidates remains a highly significant challenge worldwide. The production of panel reactive antibody （PRA） against human leukocyte antigen （HLA） is a major risk factor in presensitized recipients. The aim of this study was to evaluate the impact of HLA matching and recipients＇ PRA on two-year outcome in presensitized renal allograft recipients.
Methods We determined the percentage of panel reactivity and specificity of anti-HLA immunoglobulin （Ig） G antibodies in 73 presensitized renal allograft recipients compared with 81 unsensitized recipients （control group）. HLA genotyping of both recipients and corresponding donors was performed by PCR with sequence-specific primers （PCR-SSP）. We analyzed the factors influencing the early graft outcome （two-year rejection rates and survival rates of the grafts）, including HLA mismatching, class and degree of panel reactivity, and target antigen of donors.
Results Presensitized recipients had a worse two-year outcome than unsensitized recipients （P=0.019 for rejection rate, P=0.01 for survival rate）. The difference in number of HLA-mismatched alleles with either 6-antigen matching （Ag M） standard or amino acid residue matching （Res M） standard was not significant between the rejection and non-rejection groups of presensitized recipients or between the graft survival group and graft loss group. Compared with the control group, recipients with both PRA-I and PRA-II antibodies had a significantly worse two-year outcome （P=0.001 for rejection rate, P=0.002 for survival rate）. The two-year outcomes of the peak PRA 〉50% group and its subgroup, at-transplant PRA 〉50% group, were significantly worse compared with the control group （P=0.025 and P=0.001 for rejection rate, P=0.043 and P=0.024 for survival rate）. The rejection rates of the at-transplant target antigen positive group and its subgroup, HLA-I target antigen positive group, were significantly higher than the control group （P=0.001 and P=-0.001）, target antigen negative group （P=0.003 and P=0.001）, and peak target antigen positive with negative at-transplant target antigen group （P=0.024 and ,0=-0.002）. Two-year graft survival rates of the target antigen positive group and HLA-I target antigen positive group were significantly lower than the control group （P=0.012 and ,P=0.001）. The two-year outcome of target antigen unknown group was similar to that of the target antigen positive group. Presensitized recipients with pre-transplant plasmapheresis or immunoadsorption （PRA prepared group） had a better but non-significant two-year outcome than the control group. However, the PRA unprepared presensitized recipients were different to the control group （P=-0.004 for rejection rate and P=-0.005 for survival rate）. Hyperacute rejection （HR） occurred in three recipients with positive HLA-I target antigen and without mismatch according to Res M and in one case with positive PRA-II （for an unknown target antigen）. No HR occurred in eight cases with positive HLA-II target antigens.
Conclusions Pre-transplant PRA preparations might improve the access of presensitized patients to renal donors. Avoiding antigen-positive donors remains a fundamental measure in preventing HR and early rejections.     

双 mTORC1/2 抑制剂 AZD2014 可抑制大鼠肝移植后的急性排斥反应

目的 在同种异基因大鼠肝移植模型中验证AZD2014是否具有抑制肝移植术后急性排斥反应的作用。方法 采用Kamada 提出的“二袖套”法建立Lewis→BN 同种异基因大鼠肝移植急性排斥反应模型,随机分成对照组和AZD2014组,各4只。AZD2014组腹腔内注射AZD2014药物,5 mg/kg,1次/d;对照组腹腔内注射药物溶剂2.5 mL/kg,1次/d。不同时间点取外周血检测肝功能（丙氨酸氨基转移酶、天门冬氨酸氨基转移酶和总胆红素）。记录生存时间,进行生存分析。移植肝脏行免疫组化检测CD3和Foxp3的表达水平,评估T淋巴细胞和Treg淋巴细胞浸润的程度;移植肝脏行HE染色,采用Banff方案评估肝移植术后排斥反应的严重程度。结果 对照组在术后14 d内有3/4 的大鼠死亡,而AZD2014组在术后14 d内无大鼠死亡,AZD2014组与对照组相比生存时间明显延长（χ2=4.213,P=0.040）。对照组血清中ALT、AST和TBIL进行性升高,上述指标均高于同时间AZD2014组（P<0.05）。病理检查显示对照组移植肝内排斥反应明显重于AZD2014组（排斥指数P<0.01）,对照组中T淋巴细胞（CD3阳性）浸润相较于AZD2014组更为严重（P<0.01）,而Treg细胞（Foxp3阳性）明显少于AZD2014组（P<0.01）。结论 双mTORC1/2抑制剂AZD2014可以有效地抑制同种异基因大鼠肝移植术后的急性排斥反应。     

预致敏状态对肾移植效果的影响

目的　研究移植前预致敏状态对移植肾生存率的影响。方法　分析我院 175例次再次肾移植的 1、2、3年移植肾存活率 ,及肾移植受者术前血清群体反应抗体 (PRA )水平对移植肾存活率的影响。结果　再次移植 1、2、3年的移植肾存活率分别为 6 0 .2 %、48.5 %和 34 .4% ,明显低于首次移植的 82 .7%、71.8%和 5 0 .6 %。在近 3年32 0例淋巴毒交叉配型结果 (CDC)≤ 5 %的患者中 ,有 40例患者血清的 PRA≥ 5 0 % ,其中 14例为首次移植 ,移植肾的一年存活率为 79.5 % ,2 6例为再次移植 ,存活率为 6 1.5 % (P<0 .0 5 )。而 2 80例血清 PRA <5 0 %的患者移植肾一年存活率 ,首次移植者为 89.3% ,再次移植者为 79.2 % (P<0 .0 5 )。结论　本研究结果表明 ,移植前患者的 PRA水平以及再次移植是影响移植肾存活率的重要因素。