首页 | 本学科首页   官方微博 | 高级检索  
相似文献
 共查询到19条相似文献,搜索用时 171 毫秒
1.
目的探索异种气管移植免疫排斥反应特点,为解决供体气管来源提供新方向,并为研究肺移植继发的气道阻塞性疾病(OAD)建立理想的动物模型。方法建立SD大鼠颈部肌肉瓣包裹移植气管模型,以深低温冻储同种异体气管移植为对照,通过组织化学检查,免疫荧光检查,流式细胞术等方法,观察冷冻与非冷冻豚鼠—大鼠非协调性异种气管移植的成活情况,分析其免疫排斥反应的特点和机制。结果颈部肌肉瓣包裹深低温冻储同种异体SD大鼠长期存活。豚鼠—大鼠冷冻异种气管移植最长成活14 d,平均(13.2±0.75)d;新鲜异种气管移植最长成活9 d,平均(8.0±1.09)d。组织学检查,异体移植气管基本正常,气管通畅度大于80%。异种移植气管呈急性排斥反应表现,移植物大量嗜酸粒细胞,淋巴细胞,单核巨嗜细胞浸润;受体IgM,IgG,C3沉积;外周血CD4+T、CD8+T淋巴细胞明显升高;黏膜上皮剥脱,软骨失去活性;气管通畅度小于50%。以上表现随时间延长而加重,冷冻组弱于非冷冻组。结论细胞免疫反应参与的体液免疫反应为主的急性排斥反应是豚鼠—大鼠非协调性异种气管移植免疫反应特点。深低温冻储消减供体抗原,在一定范围内延长异种移植物成活时间。  相似文献   

2.
目的 建立豚鼠至大鼠非协调性异种肝移植动物模型,并对动脉化模型和静脉化模型进行比较.方法 共进行异种肝移植40次,其中20对为动脉化组,20对为静脉化组.比较两组存活时间、受体血中肝脏酶的变化,移植肝组织学改变和荧光抗体染色.结果 动脉化组存活时间为(92.95±28.52) min,静脉化组为(135.10±46.12) min.两组移植肝组织学变化基本相似,肝细胞水样变形、血管和血窦淤血;荧光染色见IgM和IgG沉积于血管内皮细胞和肝血窦.结论 在没有克服超急性排斥反应之前,豚鼠至大鼠异种肝移植静脉化模型比动脉化模型更简单实用.  相似文献   

3.
异种反应性天然抗体在豚鼠至大鼠肝移植中的作用   总被引:1,自引:0,他引:1  
目的 研究异种反应性天然抗体 (XNA)在豚鼠至大鼠异种肝移植超急性排斥反应(HAR)中的作用。方法 将实验鼠随机分成A、B、C、D组 ,每组 2 0只 ,分别为对照组、术前输注豚鼠肝细胞 (HC)组、术前连续肌注山地明 (CsA)组和术前输注HC合用CsA组。采用流式细胞仪和免疫组织化学方法检测受体体内XNA含量 ,观察了受体存活时间和移植肝组织学改变。结果 移植肝组织发生了HAR。受体体内存在XNA ,以IgM为主。术前输注HC使受体体内的抗体明显升高 ,A组IgM(单位 :平均荧光强度 ,下同 )为 74.58± 31 .75 ,B组为 40 6 .42± 1 0 8.0 2 (P <0 .0 1 ) ,而使用CsA能预防抗体爆发反应 ,C组为 48.82± 1 1 .0 4 (同B组比较 ,P <0 .0 1 )。术前输注豚鼠肝细胞合并使用CsA能延长受体存活时间 ,A组为 (1 2 4 .1 0± 33 .42 )min,D组为 (1 83 .70± 2 6 .85)min(P <0 .0 1 )。移植肝表现为肝细胞水样变性 ,肝血窦和血管扩张瘀血 ,但小叶结构完整。结论在豚鼠至大鼠异种肝移植中发生的HAR是一种强烈的免疫反应 ,其中XNA所起作用有限 ;术前输注豚鼠肝细胞合并使用CsA能延长受体存活时间  相似文献   

4.
异种肝细胞移植排斥机理的探讨   总被引:7,自引:0,他引:7  
目的:探讨异种肝细胞排斥反应的机理,为治疗异种肝细胞移植排斥反应提供理论依据。方法,用D-氨基半乳糖腹腔内注射制成肝功能衰竭大鼠模型,并在其脾内植入豚鼠肝细胞,通过免疫组化方法,用抗大鼠IgM抗体和抗大鼠IgG抗体,抗大鼠CD4和抗大鼠CD8抗体与因排斥反应在大鼠脾 内可能产生的IgM,IgG抗体和CD4,CD8淋巴细胞结合,在移植后不同时间取受鼠脾脏标本,检测其内是否有IgM,IgG抗体和CD4,CD8淋巴细胞存在。结果:移植后12hIgM抗体存在,移植后24h大鼠脾内出现IgG抗体,同时有CD4^=和CD8^+淋巴细胞,且在移植后1周大鼠脾内均可见上述4种物质。结论:体液和细胞免疫均参与异种肝细胞移植的排斥反应。  相似文献   

5.
目的探讨异种肝细胞移植对大鼠急性肝功能衰竭防治效果及其免疫排斥反应。方法将异种豚鼠肝细胞,90%肝除术前1d植入大鼠脾脏内。观察受试大鼠存活时间,及切肝术后24h血生化改变。另外观察植入肝细胞被排斥情况及受体CH50、异种抗体IgG、IgM水平变化。结果(1)中位存活时间,对照组为21h,同种组为56h,异种组为40h。同种组存活时间较对照组延长(P<0·01),异种组亦延长(P<0·05)。(2)异种组血糖和凝血酶原时间改善较明显(P<0·05),同种组谷丙转氨酶、总胆红素、血糖、凝血酶原时间都有明显改善(P<0·05或P<0·01)。(3)受体CH50和异种抗体IgM水平下降与植入异种肝细胞排斥过程同步。结论异种肝细胞移植对大鼠急性肝功能衰竭有防治作用,补体和异种抗体IgM与排斥反应关系密切。  相似文献   

6.
目的 研究hIL-10基因修饰的骨髓间充质干细胞(MSCs)对大鼠原位异种肝移植排斥反应的影响及机制.方法 采用豚鼠对Wistar大鼠的非协调性异种原位肝脏移植模型,实验动物随机分为3组:空白对照组,MSCs组,hIL-10-MSCs组.观察受体存活时间、受体鼠肝功能变化.术后第24小时取移植肝脏,用RT-PCR、ELISA法观察E-Selectin、LFA-1、VCAM-1及NF-κB的表达情况.结果 与空白对照组相比,hIL-10-MSCs组大鼠生存时间延长、肝功能好转,黏附分子E-Selec-tin、LFA-1、VCAM-1和NF-κB表达明显降低(P<0.05).结论 hIL-10-MSCs对移植肝脏保护作用可能与其抑制NF-κB、E-Selectin、LFA-1、VCAM-1的表达有关.  相似文献   

7.
目的 探讨补体在异种大动物猪到猴心脏移植排斥反应中的作用及机理.方法 以梅山猪为供者,中国猕猴为受者,行异种腹腔异位心脏移植.随机将受者分为3组.A组(5只):为空白对照组,受者心脏移植后不作任何处理.B组(5只):为照射预处理组,受者于心脏移植前28 d、即1.5个月龄时接受60Coγ3 Gy全身剂量照射,其余同A组.C组(8只):为照射+胸腺注射预处理组,心脏移植前21 d,将供者的脾细胞(按照5×107个/只的数量)注入受者的两侧胸腺内,其余同B组.观察心脏移植术后各组移植心的存活时间;猪对猴单向混合淋巴细胞培养的刺激效应;采用双抗体夹心法检测补体C3和CD46的血清浓度;通过流式细胞术检测受者外周血细胞表面IgM、IgG阳性细胞百分比水平.结果 A、B、C三组移植心的存活时间分别为:(36.6±5.8)h、(65.6±6.5)h和(91.1±22.8)h,C组移植心的存活时间明显延长,与A组比较,P<0.01,与B组比较,P<0.05.C组在猪对猴单向混合淋巴细胞反应中的刺激效应较A、B组明显下降(P<0.01).B、C组移植前补体水平(C3)无明显变化,但随着IgM、IgG水平的上升,发生排斥反应时C3和CD46水平显著降低.C组猕猴特异性抗猪抗体IgM及IgG的上升速度均较A、B组明显延缓.结论 对受者进行异种胸腺注射联合全身照射预处理在抑制T淋巴细胞免疫及体液免疫方面有重要作用,但无法抑制异种排斥反应中补体的激活,补体通过经典途径参与了延迟性异种排斥反应的发生.  相似文献   

8.
小鼠异种胰岛移植排斥反应研究   总被引:4,自引:0,他引:4  
目的观察小鼠对肾被膜下异种胰岛移植物的排斥反应规律和免疫病理学特点。方法将大鼠胰岛移植到小鼠肾被膜下,分别于术后当日、第1、2、4、5、6天取出移植物,研究异种胰岛排斥的病理组织学形态特点和过程。结果异种胰岛移植可有功能存活(5.9±1.2)d,在自然情况下,胰岛在术后6d左右完全被排斥,术后4d胰岛形态已不完整,单核细胞浸润明显增多。移植物附近未发现IgG+IgM的免疫沉积。结论异种胰岛的排斥反应是一个以单核细胞浸润为特征的渐进性过程,移植后4~6d达排斥高峰,CD4+T细胞可能在急性细胞性排斥反应中起重要作用,而体液免疫没有或很少参与。  相似文献   

9.
目的:了解豚鼠至大鼠异种肝移植动物模型中移植肝病理学表现。方法:利用血管套技术和显微外科技术进行了20例豚鼠至大鼠肝移植。观察了受体存活时间和移植肝HE染色情况、电子显微镜下表现和荧光染色表现。用TUNEL法检测了移植肝细胞凋亡情况。结果:受体存活时间平均为(135.10±46.12)min,组织学表现为肝小叶结构存在,但肝细胞发生弥漫性水样变性,中央静脉和小叶间静脉淤血;电子显微镜下见肝细胞内糖原颗粒消失,细胞器水肿,近血窦处肝细胞膜破坏;IgM和IgG染色主要位于肝脏血管内皮细胞表面和肝血窦内。细胞凋亡指数为(0.80±0.31)%。结论:首次建立了豚鼠至大鼠异种肝移植模型,观察了超急性排斥反应。  相似文献   

10.
猪—猴异种血管移植免疫反应初探   总被引:1,自引:0,他引:1  
目的 探讨猪-猴异种血管移植超急性排斥反应(HAR)的机理。方法 猪股静脉原位异种移植于恒河猴,发生HAR后通过免疫组化检测移植血管IgG、IgG、C3及C4的沉积。结果 大量IgM、C3和C4沉积于移植静脉内皮, 未发现IgG沉积于移植血管内皮。结论 猪-猴异种移植HAR是由异种自然抗体IgM与异抗原特异结合启动,进而以经典途径激活补体系统而发生。  相似文献   

11.
中华眼镜蛇蛇毒因子在豚鼠—大鼠异种心脏移植中的作用   总被引:2,自引:1,他引:1  
目的 应用中眼镜蛇蛇毒因子(CVF)消耗补体,观察豚鼠心脏在移植入Wistar大鼠腹腔内后对超急性排斥反应的变化。方法 按0.2μg/g体重CVF大鼠腹腔内分两次间隔6小时注射,18小时后进行心脏移植。脾切除及腹腔内注射环磷酰胺(Cy)均在移植前一天进行。设计分为四组:A组为对照组,不用任何药物;B组仅用CVF;C组应用CVF+Cy+脾切除;D组Cy+脾切除。Cy的用量为60mg/kg体重腹腔内注射。检测各组受体的供心存活时间,并在供心停跳后取出行光镜、电镜检查。结果 A、B、C、D各组供心存活时间分别为15-3120分钟。供心存活时间的统计学分析:A组与B、C两组比较P值<0.01,A组与D组比较,B组与C组比较P值>0.05,B组与D组比较,C组与D组比较P值<0.01。光镜、电镜结果提示:B、C组与A、D组有明显不同。结论 CVF能明显抑制补体活性,减轻或延缓超急性排斥反应的发生,使供体器官存活时间延长。CVF具有异种器官移植的基础研究和临床开发意义。  相似文献   

12.
Kiyochi H, Kellersmann R, Blömer A, Garcia BM, Zhang Z, Zhong R and Grant DR. Rat-to-mouse small bowel xenotransplantation: A novel model for studying acute vascular and hyperacute xenograft rejection and xenogenic cell migration. Xenotransplantation 1999; 6: 00-00. ©Munksgaard, Copenhagen Abstract: The present study was undertaken to establish a rat-to-mouse vascularized small bowel xenotransplantation model to study acute vascular and hyperacute xenograft rejection, and xenogenic cell migration. Lewis rat small bowel grafts were transplanted heterotopically to group 1, Balb/c mice, and group 2, Balb/c mice pre-sensitized with a donor spleen cell injection. The grafts were examined by serial pathology and flow cytometry. In group 1, acute vascular rejection was present by the 5th post-operative day (POD). Immunohistology showed a strong endothelial deposition of IgG, IgM and C3, associated with a minimal lymphocytic infiltrate. There was a vigorous cell migration from the recipient to the graft, in which recipient origin cells comprised 80.1± 6.9% of the graft mesenteric lymph node by POD 3. However, there was almost no cell migration from the graft to the recipient. The intestinal xenografts in the group 2 showed massive hemorrhage, fibrin deposition, vascular congestion and thrombosis 60 min after transplantation. IgG and C3 were present on the endothelium as early as 1 min after reperfusion. The vigorous humorally-mediated vascular damage and rapid elimination of donor cells seen with intestinal xenograft rejection are distinct from the usual picture of allograft rejection. Hyperacute rejection can be induced by recipient pre-sensitization with donor spleen cells. The potential advantages of studying xenotransplantation in this model include: (1) the wide range of immunologic reagents available for mice; (2) the opportunity to study the progression of vascular damage easily by performing serial biopsies in the same animal; and (3) the opportunity to study, in vivo, two-way cellular response by examining cell trafficking in the mesenteric lymph nodes.  相似文献   

13.
If effective modes of prevention of hyperacute rejection were available, the problem of the absence of enough suitable donors could be solved by the use of organ xenografts. Organ xenograft rejection is principally mediated by preformed antibodies which are responsible for the hyperacute pattern of rejection. We decided therefore to study various methods of prevention of rejection in the guinea pig to Lewis rat combination (donor-recipient discordant species) in which hyperacute rejection is particularly intense. Three series of experiments were performed. In the first series immunosuppression of the recipient was induced using an oral solution of cyclosporin A. In the second series antiplatelet-aggregation therapy was administered to the recipient, using intravenous prostacyclin (PGI2). In the third series antibody depletion of the recipient was attempted using exchange transfusion with or without prostacyclin perfusion. The most significant (p less than 0.01) prolongation of graft survival time was observed when combining exchange transfusion (8 ml) and PGI2 infusion (620 ng/kg/min). This observation suggests that, if antibody depletion in the recipient is the primary goal, measures aiming at reducing the consequences of the antigen-antibody reaction are also necessary to improve the results of organ xenografting.  相似文献   

14.
Abstract: Discordant grafting, the best alternative for future transplantation, is hampered by hyperacute rejection (HAR). Yet, there might be a difference in susceptibility to HAR between organs. In allogeneic transplantation the liver is less sensitive to antibody mediated rejection. In order to investigate whether this might also occur in discordant xenotransplantation, we performed orthotopic liver transplantation (OLT) from Dunkin Hartley guinea pigs (GP) to Brown Norway rats. Five groups were studied. In group 1, untreated controls survived for 1.5 to 4.5 hr (n = 5). In order to investigate how long a recipient could survive without a functioning graft, animals in group 2 underwent total hepatectomy (tHx) with portal-caval shunt, resulting in survival times ranging from 2 to 7 hr (n = 5). Antibody reduction by splenectomy (Spx) on day -5 (group 3) did not increase survival time (1 to 2 hr, n = 5). Complement depletion by cobra venom factor (CVF) prolonged the survival time up to 35 hr (n = 7, group 4). One animal lived for 4 days. The combined treatment of Spx and CVF resulted in similar survival times as following CVF alone, ranging from 2 hr to 6 days (n = 6, group 5). Surprisingly, none of the grafts in either of the groups showed classical signs of hyperacute rejection, like hemorrhage, edema, or obstruction of capillaries and veins as seen in the GP to rat heart transplantation model. Also liver enzyme parameters indicated no ongoing rejection. Immunohistochemistry revealed deposits of complement factors C1q, C3, and C6 on Kupffer cells but not on endothelial cells. These results indicate that, in this particular discordant model, the liver is not affected by the classical features of HAR. The beneficial effect of CVF on recipient survival therefore may rather be due to inhibition of a lethal secondary response evoked by the graft than to inhibition of HAR.  相似文献   

15.
Abstract: Background: Organ shortage impairs the proposition of multivisceral transplantation to treat multiple organ failure. Interspecies (xeno) transplantation is a valid solution for organ shortage; however, suitable models of this advance are lacking. We describe an effective model of multivisceral xenotransplantation to study hyperacute rejection. Methods: Under general anesthesia, we in block recovered the distal esophagus, stomach, small bowel, colon, liver, pancreas, spleen, and kidneys from donors and implanted heterotopically in the lower abdomen of recipients. Animals were divided into four groups: I—canine donor, swine recipient (n = 6); II – swine donor, canine recipient (n = 5); III—canine donor, canine recipient (n = 4); and IV—swine donor, swine recipient (n = 5). Groups I and II comprised experimental (xenotransplantation) and III and IV control groups (allotransplantation). During the experiment, we appraised recipient evolution and graft modification by sequential biopsy up to 3 h. At this time, we killed animals for autopsy (experimental end point). Results: We accomplished all experiments successfully. Every grafts attained customary appearance and convenient urine output immediately after unclamp. Around 15 min after reperfusion, xenografts achieved signs of progressive hyperacute rejection and absence of urine output. At the end of experiments we observed moderate to severe hyperacute rejection at small bowel, colon, mesenteric lymph node, liver, spleen, pancreas, and kidney, while stomach and esophagus achieved mild lesions. In contrast, allograft achieved normal or minimum ischemia/reperfusion injury and constant urine output. Conclusion: The present procedure assembles a simple and effective model to study multivisceral xenotransplantation and may ultimately spread researches toward hyperacute rejection.  相似文献   

16.
目的 利用眼镜蛇蛇毒因子 (CVF)、全身照射 (WBI)、异基因胸腺修饰等途径预处理受者 ,探讨这些处理对非协调性异种心脏移植物存活期及免疫排斥反应的影响。方法 供者为三色豚鼠 ,受者为SD大鼠 ,随机配对分成空白组 (O组 ) ;单用CVF的对照组 (A组 ) ;CVF +全身照射组 (B组 ) ;CVF +全身照射 +胸腺注射组 (C组 )。各组分别行大鼠腹腔内异位异种心脏移植术。观察各组供心存活时间及排斥后的光镜及电镜表现。结果  (1)存活时间 :B组、C组和A组均较O组明显延长 (P <0 .0 1) ;B组和C组又较A组明显延长 (P <0 .0 5 ) ;但C组与B组比较 ,差异无显著性 (P >0 .0 5 )。 (2 )病理表现 :O组呈超急性排斥反应 ,另三组均呈延迟性异种排斥改变。结论 在本模型中 ,使用CVF可克服超急性排斥反应 ,联用全身照射可进一步延长供心存活时间 ;但在此基础上加用异基因胸腺修饰对延长供心存活时间无显著意义。  相似文献   

17.
INTRODUCTION: The search for alternative sources for transplant organs leads us to the search for animals as an inexhaustible source of organs. The objective of this study was to analyze whether livers from polytransgenic pigs expressing the human complement regulatory proteins CD55 (hDAF), CD59, and alfa alpha1,2-fucosyltransferase (H-transferase), protected against hyperacute rejection after orthotopic liver xenotransplantation to a baboon and also to study pig liver function in a nonhuman primate. MATERIALS AND METHODS: Nine liver transplants from pig to baboon were divided into two groups: a control group (n = 4) of genetically unmodified pigs and an experimental group (n = 5) of pigs transgenic for CD55, CD59, and H-transferase as donors. All the donating piglets obtained through hysterectomy were maintained in specific pathogen-free conditions. The selection of transgenic pig donors followed demonstration of transgene expression using monoclonal antibodies (antiCD55, antiCD59) and immunohistological studies on liver biopsies. RESULTS: All animals in the control group developed hyperacute rejection with survival rates less than 16 hours without function of transplanted livers. In the experimental group none of the animals suffered hyperacute rejection. Survival in this group was between 13 and 24 hours. The livers were functional, producing bile and maintaining above 35% prothrombin activity. Only in one case was there primary dysfunction of the xenograft. CONCLUSION: Polytransgenic livers for complement regulatory proteins prevent hyperacute rejection when xenotransplanted into a baboon.  相似文献   

18.
In the guinea pig-to-rat model of hyperacute xenograft (Xg) rejection, the effect of complement inhibition using systemically administered soluble complement receptor type 1 (sCR1) on discordant cardiac Xg survival was investigated. In PBS-treated control Xg recipients (n = 13), hyperacute rejection was rapid, with a mean Xg survival of 17 +/- 4 min. Therapy with sCR1 prolonged survival of cardiac Xgs in a dose-dependent manner. A 3 mg/kg bolus of sCR1 (n = 4) prolonged Xg survival to 64 +/- 29 min (not significant). Increasing the sCR1 dose to 5.9 mg/kg (n = 4) significantly delayed Xg rejection to 71 +/- 17 min (P-0.026, log-rank test vs. control). In 10 recipients treated with 15 mg/kg sCR1, mean Xg survival was further prolonged to 189 +/- 36 min (P-0.0004) with no adverse effects. While 2 of 8 recipients receiving 60 mg/kg sCR1 died with functioning Xgs at 30 and 300 min due to anastomotic bleeding, Xg survival averaged over 12 hr (747 +/- 100 min, P-0.0004) in the remaining 6 recipients. sCR1 administration significantly inhibited serum complement activity in a parallel dose-dependent fashion, with the 60 mg/kg dose reducing complement activity by 95 +/- 1 and 96 +/- 1% five and 30 min following Xg reperfusion, respectively. Immunofluorescence microscopy revealed rat IgM bound to all cardiac Xgs in control as well as sCR1-treated recipients. In addition, serial histologic examination of cardiac Xgs harvested within 21 min of graft reperfusion revealed occlusive platelet aggregates within the coronary vessels as well as interstitial hemorrhage and myocardial necrosis in Xgs from control recipients, all of which were only minimally present in Xgs from recipients treated with sCR1. These studies show that complement inhibition with sCR1 significantly delays hyperacute cardiac Xg rejection in this discordant model and may be an important component in a therapeutic protocol for xenotransplantation.  相似文献   

19.
目的 探讨转染人白细胞介素10(Hil-10)基因的骨髓间充质干细胞(MSC)对大鼠异种移植肝脏细胞凋亡的影响.方法 以携带Hil-10基因的慢病毒Hil-10/LOX-cwGFP转染豚鼠的MSC.以豚鼠为供者,Wistar大鼠为受者,利用两套管法行原位肝移植.空白对照组的受者分别于术前24 h和术后24 h经股静脉注射生理盐水2 ml+地塞米松0.5 ml(2 mg/ml)各1次;MSC组的受者分别于上述时间点自股静脉注射2.0×106/ml的MSC单细胞悬液2 ml+地塞米松0.5 ml(2mg/ml)各1次;Hil-10-MSC组的受者分别于上述时间点自股静脉注射2.0×106/ml的Hil-10-MSC单细胞悬液2 ml+地塞米松0.5 ml(2 mg/ml)各1次.术后12 h切取移植肝脏,观察移植肝组织学变化,测定肝组织中Hil-10、凋亡蛋白酶-3(Caspase-3)、Fas和FasL的表达,观察肝细胞的凋亡情况.结果 与空白对照组、MSC组相比,Hil-10-MSC组的病理改变最轻,IL-110表达明显增加,FasL明显减少.Hil-10-MSC组的Fas和Caspase-3的阳性区域面积分别为11.5%和25.1%,明显低于空白对照组的35.3%和70.8%(P<0.05).Hil-10-MSC组的凋亡指数为32.5%,明显低于空白对照组的74.1%和MSC组的50.3%(P<0.05).结论 Hil-10-MSC可明显减轻大鼠异种移植肝脏的细胞凋亡,其机制可能与其抑制Fas/FasL的表达有关.  相似文献   

设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号