目的:研究吗替麦考酚酯(MMF)和环孢素A(CsA)对大鼠慢性移植肾病中细胞保护基因A20、HO-1、Bcl-2和Bcl-XL表达的影响。方法:分别采用雄性SD大鼠和Wistar大鼠作为供受体建立强化缺血/再灌注损伤慢性移植肾病模型。对受者依据所采用的免疫抑制剂方案分组:对照组、CsA组、MMF组。在移植术后的相同时间点处死大鼠,切取移植肾脏。采用荧光定量RTPCR和免疫组织化学方法检测A20、HO-1、Bcl2和BclXL的表达及其在移植肾中的定位情况。结果:在大鼠慢性移植肾病模型中,能够检测到所有上述四种细胞保护基因的表达。A20主要表达于血管内皮细胞和浸润之淋巴细胞。HO-1主要表达于浸润之淋巴细胞,但在肾小管上皮细胞也有表达。Bcl2和BclXL则主要表达于肾小管上皮细胞。MMF组A20的表达显著高于CsA组和对照组(Plt;0.01)。HO1,Bcl2和BclXL的表达在MMF组和CsA组间无显著性差异(Pgt;0.05)。结论:MMF对A20表达的增强可能与MMF减轻大鼠慢性移植肾病病变的机制有关。
ObjectiveTo systematically evaluate the efficacy and safety of enteric-coated mycophenolate sodium (EC-MPS) versus mycophenolate mofetil (MMF) in kidney transplant recipients. MethodsWe searched MEDLINE, EMbase, PubMed, the Cochrane Library (Issue 9, 2013), CBM, CNKI, VIP and WanFang Data from their inception to November 2013, to collect randomized controlled trials (RCTs) of EC-MPS versus MMF in kidney transplant recipients. References of included studies were also retrieved. Two reviewers independently screened studies according to the exclusion and inclusion criteria, extracted data, and assessed the risk of bias of included studies. Then, meta-analysis was performed using RevMan 5.1 software. ResultsA total of 8 RCTs involving 2 400 patients were included. The results of meta-analysis indicated that there were no significant differences between the two groups at the end of 4-week, 6-month, 12-month and 48-month follow-up in the acute rejection rate (4-weeks:RR=0.33, 95%CI 0.01 to 8.05; 6 months:RR=0.94, 95%CI 0.73 to 1.22; 12 months:RR=0.88, 95%CI 0.63 to 1.24; 4 years:RR=0.93, 95%CI 0.47 to 1.84). There were no significant differences between the two groups at the end of 6-month and 12-month follow-up in the chronic rejection rate (6 month:RR=0.66, 95%CI 0.27 to 1.58; 12 month:RR=0.57, 95%CI 0.29 to 1.15). There were no significant differences between the two groups at the end of 6-month, 12-month and 48-month follow-up in the graft loss or death rate (6-month:RR=0.79, 95%CI 0.41 to 1.50; 12-month:RR=0.76, 95%CI 0.40 to 1.43; 48-month:RR=1.38, 95%CI 0.59 to 3.23). As to the side effect, EC-MPS could significantly reduce the risk of pneumonia compared with MMF (RR=0.32, 95%CI 0.13 to 0.79). ConclusionBased on current evidences, EC-MPS is comparable with MMF for renal transplant patients in short-term effectiveness, and the incidence of pneumonia in the EC-MPS group is lower than the MMF group. Due to the limited quantity and quality of the studies, the conclusions should be validated by more high quality studies.