Humoral antibody response in rat renal allotransplantation.

Female inbred Fischer (F344) rats were grafted with kidneys from female BN rats. Humoral antibodies in some of the recipients were demonstrated as early as 3 days after transplantation: (1) antibodies bound to the graft were detected by mixed agglutination tests with graft sections and erythrocytes of the donor as indicator cells; (2) lytic and agglutinating antibodies against donor strain erythrocytes were demonstrated in the recipients' sera by hemolysis in agar gel and dextran hemagglutination tests; and (3) similar antibodies secreted by a significant number of cells were detected in the recipients' spleens by plaque assay. The antibody response of the recipients was directed against a single antigen, designated N, which was shown to be present on erythrocytes of 57% of Fischer strain rats and was shared by erythrocytes of all rat strains tested (BN, Lewis, Wistar, ACI, MAXX, and Buffalo). The N antigen did not seem to belong to any known rat histocompatibility antigen system. Segregation of the gene coding for this antigen within the Fischer strain would indicate residual genetic heterogeneity. Evidence was presented that this antigen is present not only on erythrocytes, but also on other cells including splenocytes.     

雷帕霉素对大鼠心脏移植的免疫抑制效果

为了探讨雷帕霉素对ＳＤ、Ｗｉｓｔａｒ大鼠心脏移植的免疫抑制效果，将大鼠分为３组，实验组给ＲＰＭ，对照且包括未治疗组及环孢素组。结果显示ＲＰＭ为一强效免疫抑制剂，治疗优于ＣｓＡ。ＲＰＭ具有强大的免疫抑制效果，可显著延长心脏移植物的存活时间。     

建立同种大鼠心脏移植超急性排斥反应动物模型

目的建立大鼠心脏移植超急性排斥反应的实验动物模型。方法以BN大鼠为供者，Lewis大鼠为受者。供、受者间连续进行3次皮肤移植，使受者预致敏。再进行颈部异位心脏移植。采用微量淋巴毒试验监测受者体内抗供者抗体滴度的变化。结果预致敏后的受者体内抗供者抗体滴度明显升高。7只受者心脏移植后有6只移植心在24h内被排斥，病理学证实为超急性排斥反应。结论供、受者间连续3次皮肤移植预致敏后，再行心脏移植可以建立稳定的同种移植超急性排斥反应模型。     

Orthotopic forelimb allotransplantation in the rat model

In this report, we present a rat orthotopic forelimb allotransplantation model. Eight forelimbs were transplanted from Brown Norway rats to Lewis rats. Axillary vessels of transplant were used as the vascular pedicles, which were anastomosed to the external jugular vein and common carotid artery of the recipient rat. The ulnar, radial, and median nerves were also repaired. Among rats, a tapered dose of cyclosporine was administered in five rats. In other three rats, no immunosuppressive therapy was given. The viability and signs of rejection of transplanted forelimbs, sensation recovery, bone healing, and histology were assessed up to the 90^th postoperative day. All of rats but one survived surgery. All of transplanted forelimbs survived. In the rats treated with cyclosporine the transplanted forelimbs achieved long‐term survival with motion and sensation recovery. On 90^th day after surgery, bone healing was achieved. There was no sign of rejection in histology. In the rats without cyclosporine treatment, the transplanted forelimbs experienced tissue necrosis started from day 12 postoperatively. This experimental study showed the feasibility of orthotopic forelimb allotransplantation in the rat model. © 2015 Wiley Periodicals, Inc. Microsurgery 36:672–675, 2016.     

鼠带蒂肾上腺自体移植术的研究

目的 探讨临床肾上腺带蒂移植小血管吻合方法的改进。方法 采用显微外科技术，进行鼠肾上腺带蒂移植。经假手术组（６只），双侧肾上腺切除组（６只），肾上腺移植组（６只）的术后存活观察、内分泌检测及病理检查进行比较。结果 双侧肾上腺切除组血、尿醛固酮值明显下降，平均存活６．８ｄ。而肾上腺移植组术后１、１４ｄ尿醛固酮值分别达术前的２２０．６％和１０６．１％。术后能长期存活。结论 通过显微外科技术可以成功完成     

Short-term immunosuppression after rat parathyroid allotransplantation

The aim of this study was to evaluate whether short-term postoperative immunosuppression is able to sufficiently prolong graft survival after experimental allogeneic parathyroid transplantation. Heterotopic parathyroid transplantation was performed in 6 groups: 1) syngeneic control Lewis (LEW) to LEW; 2) allogeneic control Wistar-Furth (WF) to LEW; 3-5) WF to LEW plus short-term immunosuppression, postoperative days 1-13 (cyclosporine 5/10/20 mg/kg); and 6) WF to LEW plus 10 mg/kg CyA from preoperative day 7 to postoperative day 7. Graft function was examined up to 60 days; histological and immunohistological examination was performed on all grafts with impaired function. Graft function after syngeneic transplantation was indefinite, while recipients of allogeneic grafts turned hypocalcemic after 13 +/- 2 days. With immunosuppression, graft function was 21 +/- 2 days (groups 5 and 6) and 28 +/- 3 days (groups 3 and 4). Histologically, a cellular infiltrate responsible for graft destruction was found. The results show that indefinite parathyroid allograft survival cannot be achieved by short-term immunosuppression alone. Whether the combination of an additional graft pretreatment and immunosuppression has an impact on graft function will be further examined.     

Islet of Langerhans allotransplantation in the rat.

Normoglycemia in rats allotransplanted with islets of Langerhans was studied. It was found that pretreatment with donor liver extract and pertussis followed by a short course of ALS treatment results in much better overall survival of functioning islets of Langerhans allotransplants than with other forms of immunosuppression tested.     

A new rat model of maxilla allotransplantation

We developed a rat model to test the effects of vascularized maxilla allotransplantation on composite maxillary substructures. Allograft maxilla transplantations were performed across the major histocompatibility barrier between 10 Lewis-Brown-Norway (RT1(n+l)) and 10 Lewis (RT1(l)) recipient rats under cyclosporin A monotherapy. Grafts were dissected along Le-Fort II osteotomy lines based on the common carotid artery and external jugular vein and transplanted to the anterior abdominal wall via microvascular anastomosis. Allografts were examined by tomography, flow cytometry, angiography, and histology. Three of the allografts survived up to 105 days without any signs of rejection. High level of donor-specific chimerism for T-cell and B-cell lineages was maintained in the peripheral blood. The incisors continued to grow; teeth buds, bone, cartilage, and mucosa remained intact. Moderate inflammation of the nasal, oral mucosa, and keratinous metaplasia was noted histologically. We created a maxilla allotransplantation model that allows the study of immunologic responses and demonstrates potential clinical applications based on the growth properties of the allograft.     

Use of cyclosporin A in allotransplantation of rat limbs

An experimental model for limb transplantation as a composite tissue transfer has been developed using two genetically well defined strains of rats, BUF and LEW. The study shows that cyclosporin A (CyA) is very effective as an immunosuppressive agent in preventing rejection of transplanted limbs in rats. It is found to suppress rejection of the homotransplants as long as treatment is continuous. No untoward side effects have been noted at the current experimental dosage of the medication. CyA is superior to the conventional agents, such as azathioprine and prednisolone, which allow rejection of the limbs while treatment is in progress. There is a period of immune tolerance following CyA treatment; however, this period becomes shorter as the length of the treatment is increased. This may indicate that CyA treatment should be continuous and not pulsed at the dosage used in this experimental model. Additional experiments are underway to further elucidate this phenomenon.     

冷冻保存对带血管异体关节移植排斥反应的影响实验研究

目的 观察冷冻保存和环孢霉素Ａ（ＣｙＡ）对鼠带智力这异体关节移植斥反应的作用。方法 ４０只ＳＤ大鼠随机分成４组：１组、新鲜同系移植;２组、新鲜异体移植;３组,冷冻保存异体移植;４组、冷冻保存异体移植术后用ＣｙＡ。术后进行血管造影,测定ＩＬ０－２活性及Ｔ细胞亚群（ＣＤ４／ＣＤ８）的变化,按照Ｓａｋａｉ等评分标准进行组织这评分。结果 ２组通畅率为０,与科各组比较差异有显著性（Ｐ〈０．０１）。ＩＬ－２及     

大鼠胚胎卵巢异体异位移植的研究

为了解胚胎卵巢异体异位移植后的存活和生长发育情况 ,将大鼠胚胎卵巢分别移植到去势雌鼠颈部皮下或肾被膜下 ,HE染色观察。移植后第 1 0天时移植物周围有结缔组织包裹 ,内有原始卵泡 ;移植后第 2 5天开始 ,移植物内可见大量发育卵泡及黄体与间质腺 ,移植卵巢中有丰富的血管。移植后平均 2 2天阴道上皮细胞出现周期性改变。细胞化学及免疫组织化学反应显示 :移植 3 5天后卵巢的卵泡膜内层细胞 3 -β羟甾脱氢酶呈阳性反应 ,卵巢血管内皮细胞碱性磷酸酶和 ATP酶为阳性 ;雌 ,孕激素及其受体反应强度与正常对照无明显差异。放射免疫法测定血清雌激素 ,孕激素 ,卵泡刺激素 (FSH)及黄体生成素 (L H)显示 ,移植 3 5天后 ,FSH和 L H的浓度接近正常。以上结果说明胚胎卵巢能在异体异位存活、生长发育并具有内分泌功能     

Immunological treatment with low dosage ciclosporin in rat liver allotransplantation

Ciclosporin (CsA) was administered subcutaneously at a dose of 3 mg/kg body weight/day from the day of operation to 14 days of liver allotransplantation in ACI rat (RT1a) to LEW rat (RT1(l) strain combination. All LEW recipients of ACI liver transplants without immunosuppressive treatment had severe rejection and expired within 12 days. In contrast, 7 out of 9 recipients in the same strain combination with temporary CsA treatment survived indefinitely. Histologically, widespread cellular infiltration and massive hepatocyte necrosis were evident upon autopsy of the recipients without CsA treatment. In contrast, in the surviving rats of the CsA-treated group, mononuclear cell infiltration was restricted to the periportal field and hepatocytes appeared to be normal at 14 days posttransplant. CsA concentrations in whole blood were determined by high-performance liquid chromatography. The trough levels were 788 +/- 48, 621 +/- 76 and 546 +/- 52 ng/ml, at 5, 10 and 14 days posttransplant, respectively. We concluded that this relatively low-dose subcutaneous administration of CsA offered adequate immunosuppression in rat liver allotransplantation in this strain combination.     

The immunomodulatory effect of cryopreservation in rat tracheal allotransplantation.

BACKGROUND: Cryopreservation is one solution to the problem of donor organ deficit. To investigate the effect of cryopreservation on tracheal allografts, we performed 2 experiments in rats. METHODS: In Experiment 1, we assessed second-set graft rejection. Two weeks after primary heterotopic transplantation (Group 1, fresh isografts; Group 2, fresh allografts from Lewis rats; and Group 3, cryopreserved allografts from Lewis rats; n = 5, respectively), each animal underwent secondary heterotopic grafting with isografts and allografts from Lewis and Wistar Furth rats (n = 5, respectively). Four weeks after the secondary transplantation, all grafts were retrieved for histologic analysis. In Experiment 2, we assessed the long-term results of allograft cryopreservation, without immunosuppression therapy. Six months after transplantation of fresh (Group 4) and cryopreserved (Group 5) allografts, the tracheal segments (each group, n = 5) were histologically evaluated. RESULTS: In Experiment 1, only the secondary allografts from Lewis rats in Group 2 did not maintain lumen structure and often showed dislocated or destroyed cartilage. Second-set graft rejection was specifically recognized in Group 2, but not in Group 1 or 3. In Experiment 2, the cryopreserved allografts appeared almost normal and lumen rigidity was preserved 6 months after transplantation. These allografts were superior to the fresh allografts in patency and in cartilage dislocation and mononuclear cell infiltration scores, but not in the viable chondrocyte ratio. CONCLUSIONS: We conclude that cryopreservation may produce successful long-term results because of its immunomodulatory effect on tracheal allografts.     

深低温冻储在大鼠同种异体气管移植中免疫抑制作用

目的探讨深低温冻储在同种异体气管移植中的作用.方法选择近交系Lewis大鼠自体气管移植(L-L组),及F344和Lewis行未冻储(F-L组)、冻储(CF-L组)同种异体气管移植,分别在术后2、7、30天观察各组移植段光镜下免疫排斥反应变化.结果①CF-L组在移植术后各时间点与F-L组相比较,炎细胞浸润程度及上皮下组织增殖相比显著降低(P＜0.05).②CF-L组PBMC内γ-IFN表达量在术后2、7、30天均明显低于F-L组(P＜0.01).③F-L组在移植术后2、7、30天,凋亡细胞计数均较L-L组和CF-L组高(P＞0.05).结论深低温冻储可能通过调节同种异体气管移植术后Th型细胞因子的变化和移植物细胞凋亡,从而抑制了免疫排斥反应.