共查询到18条相似文献,搜索用时 171 毫秒
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目的:研究大鼠肝移植后树突状细胞(DC)的迁移情况。方法:制作Wistar大鼠到SD大鼠的肝移植模型(实验组),并设Wistar大鼠间肝移植作为对照(对照组)。分别于术后第3、5、7天处死受者,切取移植肝组织及腹腔淋巴结,进行组织学观察,并以免疫组织化学染色观察移植肝组织和淋巴结中S-100^+DC的动态变化,以及CD25^+T淋巴细胞在淋巴结的活化增殖。结果:肝组织病理学检查显示,实验组移植后第5天即出现轻至中度急性排斥反应,至第7天发展成中至重度排斥反应,受者存活时间(9.7±1.4)d。免疫组织化学染色显示,术后第3天实验组移植肝组织中DC数量明显增多,于第5天达到高峰,第7天则出现下降,明显高于对照组,差异有统计学意义(P〈0.05)。从第3天开始,淋巴结中DC数量明显增多,第5、7天持续上升,与对照组相比,差异有统计学意义(P〈0.05)。移植术后第3天,实验组淋巴结中CD25^+T淋巴细胞明显增多,呈现明显的T淋巴细胞活化增殖反应。结论:同种异体肝移植后,DC对抗原的摄取和递呈加速,产生对T淋巴细胞强烈而持久的刺激,最终激活T淋巴细胞,导致排斥反应的发生。 相似文献
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目的 探讨外源性重组白细胞介素13(rIL-13)抑制同种肝移植大鼠的排斥反应和延长大鼠存活时间的作用及其机制.方法 以Lewis大鼠为供鼠,BN大鼠为受鼠,采用重建肝动脉的大鼠肝移植方法建立同种大鼠原位肝移植模型.采用随机数字表法将受鼠分为两组,实验组于术后第1、2、3、4和5天经尾静脉注射rIL-13 10μg/d,同期对照组注射等体积生理盐水.术后第7天,检测两组移植肝功能,测定移植肝组织病理改变、细胞因子表达及CD8+T淋巴细胞浸润等情况,并根据Banff标准计算排斥活动指数(RAI),观察术后2周的存活率.结果 与对照组相比,实验组肝功能明显改善,肝组织肿瘤坏死因子α(TNF-α)与E选择素的表达明显降低(P<0.05),CD8+T淋巴细胞浸润明显减少(P<0.05),术后2周存活率明显提高(P<0.05).实验组的RAI为4.8±1.2,明显低于对照组的7.5±1.2(P<0.05).结论 外源性重组rIL-13可减少促炎症因子TNF-α的释放和抑制E选择素的表达,减少移植物CD8+T淋巴细胞的浸润,从而减轻肝移植后急性排斥反应,延长大鼠的存活时间. 相似文献
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目的 探讨热休克蛋白70(HSP70)在大鼠肝移植术后的表达规律及对急性排斥反应的早期诊断意义.方法 采用改良"二袖套法"建立大鼠原位肝移植模型.随机将大鼠分为3组,每组供、受者各15只.对照组:供、受者均采用Wistar大鼠;未治疗组:供者为SD大鼠,受者为Wistar大鼠,肝移植后不用任何免疫抑制剂;治疗组:供者为SD大鼠,受者为Wistar大鼠,肝移植术后肌肉注射他克莫司(FK506)2 mg·kg-1·d-1.每组分别于术后第3、5、7天随机各处死5只受者,取移植肝脏观察组织病理学变化,免疫组织化学及逆转录聚合酶链反应(RT-PCR)检测移植肝HSP70的表达,并分析其与急性排斥反应的相互关系.结果 对照组术后无排斥反应发生;未治疗组术后第3天出现典型的排斥反应病理变化,随术后时间推移,排斥反应活动度积分(RAI)逐渐升高(P<0.05);治疗组表现为无排斥反应或交界性排斥反应.对照组移植肝HSP70的表达在术后出现短暂升高后迅速降低(P<0.05),未治疗组移植肝HSP70的表达水平较对照组高,并随术后时间的推移而逐渐升高(P<0.01),与移植肝RAI之间存在着明显的正相关(P<0.01);治疗组移植肝组织HSP70在术后各时间段均呈低表达.结论 移植肝组织中HSP70的表达与急性排斥反应的发生和发展密切相关;HSP70表达升高对早期诊断急性排斥反应有一定的意义. 相似文献
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目的 制备肝硬化大鼠的原位肝移植模型,观察术后排斥反应发生情况,为进行其它研究创建一个平台.方法 以皮下注射CCl4联合饮用苯巴比妥钠和乙醇溶液的方法制备大鼠肝硬化模型,应用改良的"二袖套"法建立大鼠原位肝移植模型,同系移植者的供、受者均为SD大鼠(SD实验组),以接受肝移植的正常SD大鼠为对照(SD对照组);同种移植者的供者为Lewis大鼠,受者为BN大鼠(BN实验组),以接受肝移植的正常BN大鼠为对照(BN对照组).术后观察受者的存活情况以及移植肝的组织学变化.结果 肝硬化大鼠门静脉压力为(182.0±10.7)mm H2O,显著高于正常大鼠的(70.8±5.5)mm H2O(P<0.01),移植后7 d降至(82.7±10.7)mm H2O.同种移植组术后5~12 d,移植肝组织中均可见中、重度急性排斥反应病理改变.同系移植者存活时间中位数均>100 d;同种移植者中,BN对照组和BN实验组受者肝移植后存活时间中位数均为10 d.结论 以Lewis大鼠为供者、肝硬化BN大鼠为受者制备的肝移植模型术后排斥反应的发生率较高,可作为肝移植后排斥反应相关研究的平台. 相似文献
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目的 观察Wistar-SD大鼠原位肝移植(OLT)术后发生急性排斥反应时的表现及其判断方法。方法 观察大鼠术后生存状况,采用肝功能检查及组织病理学检查等方法研究OLT模型大鼠发生急性排斥反应的表现,结果Wistar-SD实验组OLT术后发生中,重度急性排斥反应。实验组大鼠肝移植术后血清ALT,AST,TB于第1~3天及第7天各指标数值呈明显上升,高于对照组各相应时点,差异仃统计学意义(P〈0.05):结论Wistar-SD大鼠OLT模型可发生巾,重度急性排斥反应,其肝功能指标的变化可以说明急性排斥反应是否已发生. 相似文献
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目的 建立豚鼠至大鼠异种肝移植动脉化动物模型。方法 利用血管套技术和显微外科技术进行了30例豚鼠至大鼠肝移植。观察受者存活时间和移植肝组织学及超微结构变化。结果移植大鼠存活时间平均为(98.00±26.38)min,肝细胞发生弥漫性水样变性,中央静脉和小叶间静脉淤血。肝细胞内糖原颗粒消失,细胞器水肿。结论 成功地建立了非协调性异种肝移植动脉化模型。能观察移植肝的超急性排斥反应变化。 相似文献
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雷公藤多甙对大鼠原位肝移植急性排斥反应的影响 总被引:1,自引:0,他引:1
目的 探讨雷公藤多甙(TⅡ)对大鼠肝移植术后急性排斥反应的抑制作用和机制。方法 用“二袖套法”建立Wistar→SD大鼠原位肝移植模型,分对照组(n=12)和TⅡ治疗组(n=13),移植术后第7d两组各杀死部分大鼠,测肝功能、肝组织病理和脾淋巴细胞IL—2活性,其余大鼠留作观察存活时间。结果术后第7d,TⅡ组肝功能损害和移植肝病理急性排斥反应程度轻于对照组,IL—2活性低于对照组。TⅡ组大鼠术后存活时间比对照组明显延长。结论 TⅡ可明显延长肝移植术后存活时间,减轻急性排斥反应程度。 相似文献
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目的芳香烃受体(AhR)是一种配体激活性转录因子,可以影响T细胞分化,在多种免疫性疾病中发挥作用,本研究主要探索AhR在大鼠肝移植免疫应答中的作用以及机制。 方法建立大鼠肝移植同基因耐受模型和异基因排斥模型,术后1、3、7、14 d检测各组AhR和程序性死亡(PD-1)表达量。对肝移植排斥模型进行不同处理并分组。A组:对照组,腹腔注射(i.p.)羧甲基纤维素钠(CMC-Na) 1 ml;B组:200 mg·kg-1·d-1的3,4-DAA(i.p.);C组:10 mg·kg-1·d-1的CH223191(i.p.);D组:200 mg·kg-1·d-1的3,4-DAA和10 mg·kg-1·d-1的CH223191(i.p.)。7 d后采集受体外周血检测肝功能指标及CD4+Foxp3+T细胞和CD4+PD-1+T细胞占比,收集大鼠移植肝组织进行病理学检查,采用Banff分级评估排斥活动指数(RAI),并通过免疫印迹法、qPCR检测移植肝组织AhR、PD-1的变化。 结果在肝移植排斥模型中AhR和PD-1表达量随着时间逐渐降低,在肝移植耐受模型中逐渐增加。与A组相比,B组受体大鼠RAI降低,存活时间延长,移植排斥减轻;而C组肝功能指标明显上调,RAI升高,移植排斥反应加重;D组与A组差异不明显。AhR和PD-1表达以及CD4+Foxp3+T细胞、CD4+PD-1+T细胞占比在受体中呈现相同的趋势。 结论随着肝移植排斥反应的加重,AhR和PD-1表达降低,反之亦然。AhR激活可通过增加调节性T细胞的比例和PD-1的表达,有效降低大鼠肝移植排斥反应的发生。AhR有可能成为临床肝移植术后排斥治疗的新靶点。 相似文献
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阻断趋化因子受体途径对胰岛移植后急性排斥反应的影响 总被引:1,自引:0,他引:1
目的探讨趋化因子拮抗剂Met-RANTES对大鼠同种异体胰岛移植后急性排斥反应的影响及其作用机制。方法实验分2个组进行,对照组仅行胰岛移植,实验组在胰岛移植后第1~7d腹腔内注射Met-RANTES200μg/kg。术后监测大鼠的血糖变化及受者的存活情况,并观察移植胰岛的组织病理学变化;采用微量全血3H-胸腺嘧啶掺入法检测单个核细胞在刀豆蛋白A刺激下的增殖程度,流式细胞仪检测外周血CD4+细胞/CD8+细胞比值的变化及CCR5的表达。结果术后对照组和实验组血糖维持正常的时间分别为(3.8±4.5)d和(23.0±10.5)d,受者的存活时间分别为(11.4±4.2)d和(32.0±8.0)d,差异均有统计学意义(P<0.05);术后7d,对照组单个核细胞在刀豆蛋白A刺激下的增殖程度明显强于实验组(闪烁计数值分别为254.4次/min±116.3次/min和175.0次/min±98.2次/min),差异有统计学意义(P<0.05);两个组外周血CD4+细胞/CD8+细胞比值的差异无统计学意义,但对照组CCR5的表达明显强于实验组,差异有统计学意义(P<0.05);术后第7d,对照组移植胰岛周围可见较多淋巴细胞浸润,胰岛细胞减少,而实验组移植胰岛周围淋巴细胞浸润少见,移植胰岛完整。结论Met-RANTES通过阻断趋化因子受体途径抑制单个核细胞的活性;移植术后应用Met-RANTES可明显抑制大鼠胰岛移植后排斥反应的发生,显著延长移植物及受者的存活时间。 相似文献
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目的探讨大黄素对大鼠肝脏移植术后肝细胞凋亡的作用。方法建立大鼠肝移植模型,分为三组:对照组,供受体均为LEW大鼠;移植组;供体为LEW大鼠,受体为BN大鼠;大黄素组,在移植组基础上,移植术后每日以大黄素50mg·kg-1腹腔注射。分别于术后第1,3,5,7天各取6只移植大鼠的肝脏,TUNEL法染色,检测肝脏细胞凋亡。以肝脏细胞凋亡阳性细胞数占总肝脏细胞数的百分比作为肝细胞凋亡指数(AI)。结果移植组肝细胞于术后第1天即已出现凋亡,第3天明显增加,第7天达到高峰。大黄素组各时间点肝细胞凋亡指数明显小于对应的移植组(P<0.01)。结论大黄素对肝移植急性排斥反应中肝细胞凋亡有显著抑制作用。 相似文献
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近交系大鼠DA到LEW肝移植急性排斥模型的特点 总被引:1,自引:0,他引:1
目的 探讨近交系大鼠DA到LEW原位肝移植模型的特点并判断排斥反应发生的强度.方法 采用Kamada二袖套法,利用封闭群大鼠SD和Wistar进行建模技能训练,在此基础上建立近交系大鼠DA到LEW肝移植模型,根据临床表现和Banff标准判断排斥反应发生的强度.结果 共施行DA到LEW大鼠肝移植模型15例,手术成功率86.7%,死亡原因为肝上下腔静脉漏血、肝下下腔静脉血栓、胆道梗阻.术后第3天开始出现排斥反应,7 d后逐渐达到高峰,除术后并发症致死外,其余均在12 d内死于Ⅲ级排斥反应.结论 DA到LEW为稳定、强烈的大鼠肝移植急排模型,是研究肝移植排斥反应及免疫耐受的理想动物模型.但近交系大鼠在组织结构上有其自身特点,给建模带来一定难度. 相似文献
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嗅鞘细胞移植对坐骨神经切断后神经元的作用 总被引:2,自引:1,他引:1
目的研究嗅鞘细胞(olfactory ensheathing cells,OECs)移植对周围神经切断后脊髓及神经节内神经元的保护作用。方法SD大鼠55只,随机分为3个组:空白组5只、实验组及对照组各25只。行右侧坐骨神经切断,近端断端行肌肉内包埋,实验组和对照组分别予OECs及细胞培养液,空白组暴露神经后不作任何处理。术后1、2、3、7和14d,分批处死,行组织学观察及TUNEL标记观察神经元的改变。结果空白组术后14d均无阳性变化。大鼠坐骨神经切断后,脊髓及神经节内均有神经元凋亡发生。术后1、2、3d实验组细胞存活率分别为98.4%±6.5%、97.6%±6.5%及95.2%±6.7%,对照组分别为97.8%±6.7%、97.4%±6.4%及94.3%±6.8%,比较差异无统计学意义(P>0.05);7、14d实验组细胞存活率分别为92.4%±8.9%、87.7%±9.4%,较对照组87.4%±8.6%、83.4%±8.5%高,差异有统计学意义(P<0.05)。术后1、2d实验组及对照组脊髓前角运动神经元无细胞凋亡;3、7、14d实验组脊髓前角运动神经元凋亡指数分别为1.2±0.8、1.4±0.6及4.1±1.3,较对照组2.1±1.1、3.1±1.1、6.1±1.8低,差异有统计学意义(P<0.05)。术后1、2、3d神经节内细胞无凋亡;7d实验组神经节内的凋亡指数2.10±0.32,较对照组4.40±0.56低,差异有统计学意义(P<0.05);14d实验组神经节内的凋亡指数4.3±1.80与对照组6.70±2.50比较,差异无统计学意义(P>0.05)。结论周围神经损伤后脊髓及神经节内神经元有神经元凋亡发生,OECs移植对神经元凋亡有保护作用。 相似文献
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Deletion variant of hepatocyte growth factor prolongs allograft survival after liver transplantation in rats. 总被引:3,自引:0,他引:3
BACKGROUND: Despite continued progress in the development of immunosuppressive agents, allograft rejection remains an important cause of morbidity and mortality after liver transplantation. We examined the effect of the deletion variant of hepatocyte growth factor (dHGF) on allograft rejection after liver transplantation. METHODS: Male Dark Agouti rats (RT1a) were selected as donors and male Lewis rats (RT1l) as recipients for a rejection model. The recipients were divided into 2 groups after orthotopic liver transplantation (OLTx): in the dHGF group dHGF was given intravenously twice a day (1 mg/kg/day) after OLTx, whereas in the control group vehicle buffer was given intravenously daily twice after OLTx. The survival period, serum chemistry studies, and histopathologic findings were then compared between the 2 groups. RESULTS: The mean survival period after OLTx in the dHGF group was significantly longer than that in the control group (21.4 +/- 1.3 days vs 11.8 +/- 0.4 days, P < .001). On the 10th posttransplant day the serum albumin level significantly improved in the dHGF group (P < .01), and the serum total bilirubin and aspartate aminotransferase levels were significantly lower in the dHGF group (P < .01 and P < .05, respectively). On the 10th posttransplant day a histologic examination revealed no apparent difference in the severity of rejection between the 2 groups. The number of proliferating cell nuclear antigen-positive hepatocytes in the dHGF group significantly increased (P < .01), whereas the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling-positive hepatocytes were significantly reduced in the dHGF group (P < .01) in comparison with those in the control group. CONCLUSION: dHGF has an antiapoptotic property as well as a proliferative and protective effect on hepatocytes under allograft rejection. dHGF might serve as a novel agent for reducing the harmful effects of hepatic allograft rejection in rats. 相似文献
16.
Hynek Mergental Jan Kriz Eva Honsova Michal Kudla Tomas Pantoflicek Katerina Tcherentsova Matej Kocik Frantisek Saudek Miroslav Ryska 《Transplant international》2004,17(11):687-691
Abstract Our study was designed to determine effect of gemcitabine on acute rejection of liver in rats. Liver transplantation was performed in rats of the Dark Agouti (DA) and Lewis (LEW) strains. Recipients were divided into three groups: A, DA-to-LEW without immunosuppression; B, DA-to-LEW, treated with cyclosporine A; C, DA-to-LEW, treated with gemcitabine. Immunosuppressants were subcutaneously injected for seven consecutive days after transplantation. On day 7, blood samples and liver graft tissue specimens were harvested. Group A showed severe rejection changes (RAI 8/9); in group B no rejection changes were present (RAI 0/9), and in group C moderate rejection changes were observed (RAI 6/9). Differences were significant between B vs C and A vs C groups; P >0.05. Serum creatinine and urea levels in the gemcitabine group were significantly lower than those in the cyclosporine A group. We did not confirm gemcitabine ability to prevent liver allograft rejection. 相似文献
17.
Hynek Mergental Jan Kriz Eva Honsova Michal Kudla Tomas Pantoflicek Katerina Tcherentsova Matej Kocik Frantisek Saudek Miroslav Ryska 《Transplant international》2005,17(11):687-691
Our study was designed to determine effect of gemcitabine on acute rejection of liver in rats. Liver transplantation was performed in rats of the Dark Agouti (DA) and Lewis (LEW) strains. Recipients were divided into three groups: A, DA-to-LEW without immunosuppression; B, DA-to-LEW, treated with cyclosporine A; C, DA-to-LEW, treated with gemcitabine. Immunosuppressants were subcutaneously injected for seven consecutive days after transplantation. On day 7, blood samples and liver graft tissue specimens were harvested. Group A showed severe rejection changes (RAI 8/9); in group B no rejection changes were present (RAI 0/9), and in group C moderate rejection changes were observed (RAI 6/9). Differences were significant between B vs C and A vs C groups; P<0.05. Serum creatinine and urea levels in the gemcitabine group were significantly lower than those in the cyclosporine A group. We did not confirm gemcitabine ability to prevent liver allograft rejection. 相似文献
18.
D Grant R Zhong D Hurlbut B Garcia H F Chen D Lamont P Z Wang C Stiller J Duff 《Transplantation》1991,51(5):948-954
Two surgical techniques are commonly used for small intestinal transplantation: heterotopic (accessory) intestinal grafting (HIT), where the small bowel is initially defunctioned with restoration of intestinal continuity at a later date, and orthotopic (in continuity) intestinal grafting (OIT), where the small bowel is immediately anastomosed to the native intestine. The present experiments were undertaken to compare the advantages and disadvantages of these two surgical models. Graft barrier function (intestinal permeability), intestinal histology, and graft survival were evaluated after heterotopic and orthotopic intestinal transplantation in the following groups of rats: group 1: isografts, group 2: untreated allografts, group 3: low-dose cyclosporine-treated allografts (subcutaneous CsA 2 mg/kg/day), and group 4: high-dose CsA-treated allografts (subcutaneous CsA 4 mg/kg/day). Intestinal permeability was consistently higher after HIT than OIT in all of the groups (ANOVA; P less than 0.01). Histological evidence of rejection appeared earlier after HIT than OIT (HIT 5th postoperative day (POD); OIT 7th POD; P less than 0.05). The mean survival of untreated allografts was longer after HIT than OIT (HIT 15.7 +/- 6 days, OIT 9.2 +/- 1 days, P less than 0.05). The rats treated with low-dose CsA after OIT lost weight and died of rejection after a mean survival time of 17.7 +/- 2 days, while the rats treated with low-dose CsA after HIT remained well until sacrifice on POD 28 (P less than 0.01). The rats with isografts and rats with allografts treated with high-dose CsA remained well after HIT and OIT until sacrifice on the 28th POD. These data suggest that nutrients and other factors in the succus entericus may improve gut barrier function and delay the onset of rejection after OIT. However, rejection of the orthotopic intestinal graft is usually fatal, while rejection of the heterotopic graft is often surprisingly well tolerated. These factors must be taken into consideration when choosing a surgical technique for intestinal transplantation in humans. 相似文献