免疫毒素IL-2-PE66抑制小鼠角膜移植免疫排斥反应的研究

目的 观察新型免疫抑制毒素白细胞介素-2-绿脓杆菌外毒素(interleukin-2-pseudomonas exotoxin66,IL-2-PE66)对小鼠角膜移植排斥反应的免疫抑制疗效.方法 建立小鼠同种异体穿透性角膜移植模型.36只鼠随机分为IL-2-PE66治疗组及生理盐水对照组,临床观察两组角膜植片免疫排斥反应发生的时间和程度,并在术前及术后第10、15、25、35天分别取出鼠眼行组织病理学检查,同时收集外周血行T淋巴细胞亚群及T淋巴细胞集落形成数分析.结果 治疗组与对照组植片存活时间分别为(31.2±2.9)d和(15.8±2.1)d,术后第15天治疗组与对照组T淋巴细胞亚群CD_4~+/CD_8~+比率分别为(1.26±0.23)和(2.01±0.23),T淋巴细胞集落形成数分别为(201±18.2)和(286±16.8). 结论 IL-2-PE66可推迟角膜移植排斥反应的发生时间;有明显减少外周血中辅助T淋巴细胞百分率的作用;并能减弱小鼠外周血T淋巴细胞集落形成能力.提示IL-2-PE66是一种高特异性的免疫抑制剂.

Abstract：

Objective To study the immunosuppressive effect of the interleukin-2-pseudomonas exotoxin 66(IL-2-PE66) on murine corneal allograft rejection. Methods Thirty-six recipient female BALB/c mice received corneal allografts from C57BL/6 mice and were divided randomly into treatment and control groups. The condition of the grafts was observed twice a week. On days 10, 15, 25 and 35 after the transplantation, the operated eyes were removed for pathological examinations. Peripheral blood samples were also collected for analysis of T cell subsets and T lymphocyte colony forming unit (T-CFU) assay. Results The survival time of corneal allograft averaged 15.8±2.1 days in the control group and 31.2±2.9 days in the treatment group. The CD_4~+/CD_4~+ of the T cell subsets 15 days after the operation was 1.26±0.23 in the treatment group and 2.01 ±0.23 in the control group, with T-CFU of 201 ±18.2 and 286+16.8, respectively. Conclusion IL-2-PE66 can delay the development of comeal graft rejection, significantly reduce the percentage of T helper cells, and weaken the aggregation of the peripheral T cells.     

Combined use of Ad-hENDO-VEGI151 and Dexamethasone for prevention and treatment of keratoplasty rejection.an experimental study

Objective:To evaluate the probability and efficacy of endostatin-vascular endothelial growth inhibitor (VEGI) recombinant adenoviruses combined with dexamethasone on suppressing heterolamellar corneal transplantation rejection. Methods: Heterolamellar corneal transplantation models were established in 64 New Zealand rabbits, which were randomized into 4 groups of 16 rabbits each. After the transplantation, all the 64 right eyes were injected subconjunctively with 0. 2 ml saline (saline group), 0. 1 ml AdCA13-hENDO-VEGI151 plus 0. 1 ml saline (AdCA13-hENDO-VEGI151 group), 0. 1 ml Dexamethasone (DXM) plus 0. 1 ml saline (DXM group), 0. 1 ml AdCA13-hENDO-VEGI151 plus 0. 1 ml DXM (Ad-CA13-hENDO-VEGI151 combined with DXM group) with one time each 3 days for 10 times. Graft survival and ocular surface were observed for 6 weeks. The fusion protein expression was detected by immunohistochemistry 6 weeks after transplantation. Results: Both the CNV index, rejection index and the xenograft rejection rate in the AdCA13-hENDO-VEGI151 combined with DXM group were statistically lower than those in other groups. AdCA13-hENDO-VEGI151 combined with DXM group: 1. 375 0±0. 500 0, 2. 750 0 ±1. 843 9 and 6. 25% respectively 6 week after keratoplasty; Saline group: 3. 437 5±0. 512 3, 8. 812 5± 1.1087, 100.00%; AdCAl3-hENDO-VEGI151 group: 2. 312 5±0. 478 7, 5. 625 0±0. 957 4, 62.50%; DXM group: 3. 000 0±0. 816 5, 5. 562 5±1. 315 0, 56.25% (P<0. 01). Immunohistochemical staining showed the fusion protein expressed mainly in corneal epithelium. Conclusion: The fusion protein expressed by the recombinant adenovirus has significant effect on inhibiting neovascularization after heterolamellar corneal transplantation. The topical application of AdCA13-hENDO-VEGI151 combined with DXM suppressed effectively the postoperative xenograft rejection rate of heterolamellar corneal transplantation.     

Impact of MAPK Cascade Pathway and P53 Pathway upon Liver Transplant

Summary： The change and the role of MAPK cascade pathway and P53 pathway after liver transplantation were explored. Thirty-four punctured donor liver specimens and 10 normal liver specimens were classified as group A （no rejection, n=10）, group B （mild/moderate acute rejection, n=10）, group C （serious acute rejection, n=8）, group D （chronic rejection/fibrosis, n=6） and group E （control, n= 10）. By using immunohistochemistry, the expression levels of mitogen activated protein kinase （MAPK）, Ras and P53 proteins, and by in situ hybridization, MAPK and ras mRNA expression levels were detected. The results showed that the expression levels of MAPK and Ras proteins were increased by turns in groups A, B and C, and decreased by turns in groups D and E. The protein expression of P53 was higher in the treated groups. The expression of Ras, HSP70 mRNA was identical as that of protein. It is suggested that the MAPK cascade pathway and P53 pathway can protect the hepatocytes by different mechanisms after liver transplantation. MAPKs cascade pathway repairs hepatocyte injury or accelerates hepatocytes into proliferation or differentiation. P53 pathway blocks cell cycle within G1 phase to make hepatocyte repair or apoptosis to reduce disorder differentiation.     

Expression of fractalkine and its receptor in acute cardiac allografts rejection

Objective To investigate the expression of fractalkine(FKN) and its receptor CX3CR1 in cardiac allografts and the effect of Cyclosporin A(CsA). Methods Three groups of rats underwent heterotopic cardiac transplantation, 45 cases in each group and 5 cases in control group:SD to SD regarded as isograft group (group A), Wistear to SD divided into CsA untreated allograft group(group B) and CsA treated allograft group (group C), normal SD rats as control group. The FKN mRNA expression was detected by one-step RT-PCR method and the expression of FKN and CX3CR1 protein was detected by standard ABC immunohistochemical technique. Results The expressin of FKN mRNA and protein was weak in both isografts and normal heart specimens. The changes of FKN mRNA expression were correkted with the process of acute allograft rejection. The peak of FKN mRNA expression(0.8 ±0.26) appeared on the seventh day after transplantation, which could be downregulated by CsA significantly ( t = 2.390, P < 0.05). FKN protein was locate     

Response of the xenograft endothelium in the concordant xenotransplantation

Objective: To investigate the response of the xenograft endothelium in the concordant hamster to rat cardiac xenotransplantation and the mechanism of acute vascular rejection. Methods: The animals were divided into 5 groups randomly: control group,CsA group, splenectomy group, D0 splenectomy CsA group and D3 splenectomy CsA group. Hamster heart was heterotopicaly transplanted to rat abdominal cavity. The graft survival was monitored by palpation of the rat abdominal wall. The histological and ultrastructural changes of the xenogafts were investigated. NF-κB and P-selectin expression in the xenograft were detected. Hene Oxigenase-1 and Bcl-2 expression were also detected in the xenografts of different groups. Results: The mean survival time of the xenografts in control group, CsA group, splenectomy group, D0 splenectomy CsA group and D3 splenectomy CsA group was 3.4±0.55, 3.8±0.45, 6.4±1.52, 30 and 7.4±1.14 days. The rejected graft showed typical acute vascular rejection in control group, CsA group,splenectomy group and D3 splenectomy CsA group. Endothelial cells of the rejected xenograft showed dramatic assembly of ribosomes and expansion of the rough endoplasmic reticulum. However, the endothelium of the long-term survived grafts in D0 splenectomy CsA group showed normal architecture. NF-κB and P-selectin expression were detected in the rejected xenografts. HO-1 expression was observed in the long-term survived xenografts in D0 splenectomy CsA group. Conclusion: The endothelial cells of the xenograft might be activated during the acute vascular rejection. Expression of HO-1 might inhibit the upregulation of NF-κB and adhesion molecular which decreases the activation of the endothelium of the graft.     

Significance of Rosiglitazone Inhibiting TLR4 Expression in Partial Hepatic Ischemia/Reperfusion of Mice

The effect of rosiglitazone as the ligand of peroxisome proliferator-activated receptor γ (PPARγ) inhibiting the TLR4 expression in ischemic lobes in partial hepatic ischemia/reperfusion injury (IRI) in BABL/C mice and the action of rosiglitazone inhibiting the TLR4 receptor-mediated inherent immune response were investigated. The model of the mouse partial hepatic ische- mia/reperfusion injury was established. All the animals were randomly divided into 3 groups: rosiglitazone group, vehicle (dimethylsulphoxide, DMSO) group and sham operation group. The hepatic samples were collected when mice were sacrificed 0, 2, 4 and 6 h after reperfusion following 1 h ischemia to analyze the acute phase of hepatic IRI. The dynamic expression of TlR4 mRNA was de- tected quantitatively by real-time-PCR, and the levels of TNF-α, IL-10 and ALT in portal vein were determined in all groups. After restoration of blood supply, the expression of TLR4 mRNA in ischemic lobes was detected in 0, 2, 4 and 6 h after reperfusion following 1 h ischemia in rosiglitazone group and vehicle group. The most intensive expression of TLR4 mRNA was present at 4 h after reperfusion in ischemic lobes in vehicle group. As compared with vehicle group, the expression of TLR4 mRNA in ischemic lobes in rosiglitazone group was significantly decreased at 4 h after reper- fusion. The level of IL-10 in portal vein was markedly up-regulated in rosiglitazone group as compared with vehicle group. Contrarily, the levels of TNF-α and ALT in portal vein were markedly down-regulated in rosiglitazone group as compared with vehicle group at every time point in mouse partial hepatic IRI model. Rosiglitazone could alleviate the hepatic IRI by inhibiting TLR4 receptor-mediated inherent immune response.     

Application of human leukocyte antigen and cross-reactive group matching in clinical renal transplantation

Objective To investigate the application and significance of human leukocyte antigen (HLA) and cross-reactive groups ( CREGs) matching in clincal renal transplantation. Methods A total of 312 cases of kidney transplantation were divided into two groups. In one group of 149 cases of kidney transplantations, Class I CKEGs matching criteria were applied instead of conventional HLA - A, B matching which had two A, B mismatches (MM). In the other group of 163 cases of kidney transplantation there were A, B 0 - 2 MM by the conventional criteria. The graft survival rate at 1 year and incidence of acute rejection within 1 month after transplantation were compared between the 2 groups. Results The perecentages of HLA-I antigens 0,1,2 MM were 16.7% ,41.6% and 34.2% by CREGs matching criteria, and were 6.7%, 21.5% and 71.8% by conventional matching criteria. The matching rates in CREGs 0,1 MM group were significantly higher than those in corresponding conventional matching group ( P < 0.01). There were no signific     

Effects of Propofol on The mRNA Expression of Toll-like Receptor 4 in BV-2 Cells During Mimic Ischemia-Reperfusion Injury In Vitro

This study investigated the effects of propofol on the mRNA expression of Toll-like receptor-4 (TLR4) in BV-2 cells during mimic ischemia-reperfusion (I/R) injury in vitro. BV-2 cells, a mouse microglia line, were cultured and divided into 4 groups at random: control group (group C), ischemia/reperfusion group (group I/R), low-dose propofol (25 μmol/L) intervention group (group PF25) and high-dose propofol (100 μmol/L) intervention group (group PF100). The mRNA expression of TLR4 and NF-κB was measured by means of RT-PCR. TNF-α levels in the supernatants of BV-2 cells were detected by ELISA. The results showed that the mRNA expression of TLR4 and NF-κB was significantly higher in groups I/R, PF25 and PF100 than in group C (P<0.01). And the TNF-α level in the supernatants was elevated in groups I/R, PF25 and PF100 as compared with that in group C (P<0.01). After pre-treatment with propofol, the mRNA expressions of TLR4 and NF-κB and the TNF-α level were significantly decreased in groups PF25 and PF100 in comparison to those in group I/R (P<0.01). And the decrease in those indicators was more significant in group PF100 than in group PF25 (P<0.01). It was concluded that propofol exerted brain-protecting effects during I/R injury by suppressing the mRNA expressions of TLR4 and NF-κB and deceasing the TNF-α level.     

基质细胞衍生因子-1与趋化因子受体4在大鼠角膜移植排斥反应中的作用

目的 探讨基质细胞衍生因子-1(SDF-1)与基质细胞衍生因子-1(CXCR4)在大鼠角膜组织中的表达及其在角膜移植术后免疫排斥反应中的作用.方法 取15只Wistar大鼠作为正常对照组;取22只Wistar大鼠行自体角膜移植术作为自体组;取22只SD大鼠与44只Wistar大鼠,以SD大鼠为供体,Wistar大鼠为受体行穿透性角膜移植,术后随机抽取22只归入典必殊组,术眼滴典必殊眼液(每日2次),剩余22只归入异体组,术眼滴同等量生理盐水,共一个月.参照Larkin法对各组角膜植片进行临床评估;分别于术后第5、9天取术眼角膜植片,行组织病理学观察、免疫组化检查、实时荧光定量PCR检测.结果 自体组不发生排斥反应,典必殊组角膜存活时间为24±0.32 d,远高于异体组10±0.36 d (P＜0.001).组织病理学检查发现异体组角膜有大量炎性细胞浸润以及新生血管形成.SDF-1和CXCR4 mRNA在异体组角膜组织中表达水平明显升高(第5天P＜0.001,第9天P＜0.01),典必殊组较异体组明显降低.免疫组化检查发现SDF-1/CXCR4主要表达在角膜植片的上皮层与基质层,异体组角膜组织SDF-1和CXCR4含量明显升高.结论 SDF-1/CXCR4可能参与了大鼠角膜移植术后早期的排斥反应,其机制可能为SDF-1特异性诱导CXCR4+细胞成熟和朝着排斥部位趋化,并促进角膜新生血管形成.     

CD86在大鼠角膜移植排斥反应中的表达及意义

目的观察大鼠角膜组织中共刺激分子CD86(B7-2)的原位表达,以了解共刺激分子在大鼠角膜移植排斥反应中的作用和意义。方法制作大鼠角膜移植模型,观察角膜透明度、新生血管。采用免疫组化法检测CD86在角膜、脾脏组织中的表达。结果术后角膜植片均出现不同程度的新生血管,角膜水肿、混浊,基质增厚。CD86在正常的角膜组织中无阳性表达;在移植后出现急性排斥反应的角膜上皮层中有大量阳性细胞表达。在脾脏的阳性细胞表达与文献报道的一致。结论共刺激分子CD86在移植后发生排斥的角膜组织中的阳性表达,可能与免疫排斥反应有关。     

CD86在大鼠角膜移植排斥反应中的表达及意义

目的 观察大鼠角膜组织中共刺激分子CD86(B7-2)的原位表达，以了解共刺激分子在大鼠角膜移植排斥反应中的作用和意义。方法 制作大鼠角膜移植模型，观察角膜透明度、新生血管。采用免疫组化法检测CD86在角膜、脾脏组织中的表达。结果 术后角膜植片均出现不同程度的新生血管，角膜水肿、混浊，基质增厚。CD86在正常的角膜组织中无阳性表达；在移植后出现急性排斥反应的角膜上皮层中有大量阳性细胞表达。在脾脏的阳性细胞表达与文献报道的一致。结论 共刺激分子CD86在移植后发生排斥的角膜组织中的阳性表达，可能与免疫排斥反应有关。     

CD25单克隆抗体对大鼠角膜移植术后房水中细胞因子表达的影响

目的 研究CD25单克隆抗体对大鼠角膜的毒性以及对同种异体大鼠角膜移植后房水中细胞因子的影响.探讨其对大鼠角膜移植免疫排斥反应的防治效果.方法 ①将12只SD大鼠随机分为生理盐水对照组、50μg CD25单克隆抗体结膜下注射组、100μg CD25单克隆抗体结膜下注射组、200μg CD25单克隆抗体结膜下注射组,每组3只.各组大鼠均右眼用药.分别于0、2、4、6、8d结膜下注射生理盐水及不同剂量的CD25单克隆抗体,共5次.每日行裂隙灯显微镜检查.观察角膜有无水肿、混浊发生.并于第9天取右眼角膜行病理及透射电镜观察角膜各层的变化.②以Wistar大鼠为供体,SD大鼠为受体建立角膜移植实验模型.将93只SD大鼠随机分为五组,A组:正常组;B组:角膜移植对照组;C组:CD25单克隆抗体治疗组;D组:CD25单克隆抗体联合地塞米松治疗组;E组:地塞米松治疗组.B组术后给予生理盐水;C组术后给予CD25单克隆抗体100 μg;D组术后给予CD25单克隆抗体100μg联合地塞米松50 μg治疗;E组术后给予地塞米松100μg;各共用5次,分别于术后0、2、4、6、8 d经球结膜下注射给药.用裂隙灯观察移植排斥情况.利用逆转录-多聚酶链反应检测植片内IFN-γmRNA的表达,酶联免疫吸附法检测房水中IFN-γ和IL-4的浓度.结果 ①50μgCD25单克隆抗体和100μgCD25单克隆抗体对角膜基本无影响;200μg的CD25单克隆抗体组透射电镜检查发现角膜基质细胞及内皮细胞有不同程度的肿胀.②C、D、E组发生排斥反应时间分别为(13.167±1.169),(17.333±2.160),(16.417±1.379)d较B组发生排斥反应时间(10.583±1.084)a明显延迟,差异有统计学意义(p＜0.05).正常角膜无IFN-γmRNA的表达,术后11天.B组移植角膜植片内IFN-γmRNA的表达较C、D、E组明显增强(p＜0.05).C、D、E组术后6 d及11 d房水巧N叫的含量明显低于同期的B组(p＜0.05);同C组相比,术后11d D、E组房水IFN-γ的含量明显降低(P＜0.05).术后6 d和11 d,与B组相比,同期C组IL-4含量明显升高(P＜0.05),而同期D、E组IL-4含量明显降低(P＜0.05);术后6 d和11 d,与C组相比,同期D、E组IL-4含量明显降低(P＜0.05).结论 50μg CD25单克隆抗体和100 μgCD25单克隆抗体对角膜基本无影响.IFN-γ和IL-4在角膜移植免疫排斥反应过程中发挥重要的作用.CD25单克隆抗体通过抑制Th1因子(IFN-γ)、促进Th2因子(IL-4)表达降低角膜移植免疫排斥反应的发生率,从而延长角膜植片存活时间;而CD25单克隆抗体联合地塞米松治疗通过同时抑制Th1因子(IFN-γ)、Th2因子(IL-4)表达,却更能延长角膜植片的存活时间,具有重要的临床应用价值.     

树突状细胞在大鼠穿透性角膜移植排斥反应中的作用

目的 观察大鼠角膜组织中树突状细胞的分布,以了解树突状细胞在穿透性角膜移植排斥反应中的作用.方法 制作大鼠穿透性角膜移植模型,观察角膜透明度、新生血管.采用免疫组织化学方法检测OX-62 树突状细胞在角膜的分布.结果 术后角膜植片均出现不同程度的新生血管、角膜水肿、混浊、基质增厚.排斥反应发生率100%.正常角膜组织中未见OX-62 树突状细胞分布,在发生急性排斥反应的角膜上皮层中有阳性细胞表达.脾脏阳性细胞表达与文献报道一致.结论 OX-62 树突状细胞出现在移植后发生排斥的角膜组织中,角膜组织中的树突状细胞可能参与角膜移植后的免疫反应.     

穿透性角膜移植术后免疫排斥反应高危因素分析

目的 分析穿透性角膜移植术后免疫排斥反应的高危因素。寻找角膜移植术后免疫排斥反应的有效防治方法。方法 对穿透性角膜移植术后发生免疲排斥反应的31例，从角膜盲原因、植床新生血管程度、合并症、移植片直径、联合手术等5大高危因素进行回顾性分析。结果 血管化角膜、大植片移植、植床术前的活动性炎症、偏中心移植、多次移植、联合手术等应视为穿透性角膜移植术后免疲排斥反应的高危因素，而移植片上皮反复脱落、眼压高、旧病复发、术眼再次手术、缝线松解与拆线等可能是诱导排斥反应发生的促发因素。结论 尽量减轻角膜血管化，掌握适当的手术时机，强调病人的及时复诊和治疗，术后坚持局部使用免疲抑制剂半年，排斥发生时及时足量地全身及局部使用激素和免疲抑制剂，均可以在一定程度上帮助控制免疲排斥反应。     

雷帕霉素抑制大鼠高危角膜移植免疫排斥反应的实验研究

目的：研究雷帕霉素对大鼠高危角膜移植免疫排斥反应的抑制作用。方法：建立大鼠高危穿透性角膜移植动物模型，以角膜新生血管化sD大鼠为受体。Wistar大鼠为供体，分别腹腔注射0．5％羧甲基纤维素（对照组）、雷帕霉素、环孢霉素A、雷帕霉素＋环孢霉素A，共12d。用裂隙灯显微镜对角膜植片进行临床观察，记录角膜植片存活时间，并进行组织学检查。结果：用药组角膜植片的存活时间显著增加（P〈0．01）；组织学发现联合用药组的角膜炎性细胞浸润、新生血管形成度水肿程度均明显好于其他各组。结论：雷帕霉素能显著延长角膜植片的存活时间，对大鼠高危穿透性角膜移植排斥反应具有抑削作用，与环孢霉素A联合用药具有协同作用，优于各单药物治疗组。     

Effects of 1alpha, 25-dihydroxyvitamin D3 on the acute immune rejection and corneal neovascularization in high-risk penetrating keratoplasty in rats]

OBJECTIVE: To investigate the effects of 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)), a hormone that has immunosuppressive properties, on acute rejection and corneal neovascularization in rat keratoplasty model, so as to assess the therapeutic effects and explore the mechanism of 1,25(OH)(2)D(3) as an immunosuppressant in corneal transplantation. METHODS: High risk corneal transplantation was performed orthotopically in SD rat models of high risk penetrating keratoplasty established by placing three 10-0 nylon sutures in the central corneas for two weeks, with the Wistar rats as the donors. The SD rat models were randomly assigned into 5 groups and treated with 1,25(OH)(2)D(3) at varied concentrations and cyclosporine A (CsA). The expressions of interleukin (IL)-1alpha, tumor necrosis factor (TNF)-alpha, and vascular endothelial growth factor (VEGF) mRNA were detected by in situ hybridization (ISH). RESULTS: 1,25(OH)(2)D(3) significantly suppressed acute graft rejection and inhibited corneal neovascularization as compared with saline. 1,25(OH)(2)D(3) showed better immunomodulatory effects when administered along with CsA in rat corneal allotransplants. ISH study demonstrated that 1,25(OH)(2)D(3) strongly suppressed mRNA and protein expressions of the cytokines IL-1alpha and TNF-but not those of VEGF. CONCLUSION: Topical administration of 1,25(OH)(2)D(3) can be effective in suppressing acute corneal graft rejection by inhibiting the expression of proinflammatory cytokines (IL-1alpha and TNF-alpha).     

Effect of a cyclosporine A delivery system in corneal transplantation

目的　探讨前房内植入含环孢素A的缓释系统 (CsADDS)抑制高危角膜移植术后免疫排斥反应的有效性和可行性。方法　角膜新生血管化的近交系Wistar大鼠作为受体 ,供体取自SD大鼠 ,行穿透性角膜移植的大鼠随机分为 4组 :(1)对照组 ;(2 )CsADDS前房植入组 ;(3)CsADDS结膜下植入组 ;(4) 1%CsA橄榄油滴眼组。植片每 3天行裂隙灯显微镜检查并加以评估。分别于术后 1、2、4周行房水中CsA浓度的检测。移植后的 1、2、4周取眼球行组织病理学检查。结果　角膜植片平均存活时间分别为 :对照组 8 2± 1 4 8天 ;CsADDS结膜下植入组 11 4± 2 5 0天 ;前房植入CsADDS组 17 0± 2 0 0天。前房植入组与其它各组相比 ,有显著统计学差异 (P <0 0 5 )。相对于其它治疗组前房植入组的眼内CsA浓度明显增高 ,并且发现CsA聚合物的植入体在前房中只引起轻微而短暂的炎症反应。结论　前房植入CsA聚合物可明显延长高危角膜移植术后的植片存活时间 ,这一眼内缓释系统对于抑制高危角膜移植术后的免疫排斥反应不失为一种有效方法。     

兔同种异体角膜缘移植术后免疫排斥反应的实验研究

目的：本研究旨在探索同种异体角膜缘移植免疫排斥反应规律并观察环孢霉素A（CsA）滴眼液的免疫抑制作用。方法：32只新西兰白兔随机分成实验组和CsA对照组．建立右眼角膜缘缺陷症动物模型，1月后实施同种异体角膜缘移植术，术后分别予生理盐水及1％CsA眼液滴眼并观察4周。术前1天及术后1～8周动态监测外周血T淋巴细胞上CD25的表达；分别取术后第4、8及10周的角膜缘植片观测淋巴细胞浸润及T淋巴细胞上CD25的表达。结果：实验组术后第1周外周血表达CD25的T淋巴细胞数就有增高，第3周已达到高峰，第5周开始缓慢下降。CsA组角膜缘植片中浸润的淋巴细胞及表达CD25的T淋巴细胞数目显著低于实验组。结论：同种异体角膜缘移植术后排斥反应的发生与表达CD25的T淋巴细胞数目密切相关：CsA眼液可抑制外周血及植片中T淋巴细胞上CD25的表达，从而抑制排斥反应发生。