Basic Studies on Liver Transplantation and Liver Preservation
肝移植与肝脏保存的基础研究
基本信息
- 批准号:01480328
- 负责人:
- 金额:$ 4.35万
- 依托单位:
- 依托单位国家:日本
- 项目类别:Grant-in-Aid for General Scientific Research (B)
- 财政年份:1989
- 资助国家:日本
- 起止时间:1989 至 1991
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
First Research : The protective effect of the immunosuppressive drug FK506 on warm ischemic injury of pig liver was studied as research of liver preservation.Second Research : The incidence of ulcer is very high after orthotopic liver transplantation in young pigs. Therefore we studied the pathogenesis of gastric ulcer following pig liver transplantation and its prevention by vagotomy-pyloroplasty.Third Research : To prevent rejection effectively, allograft recipients usually receive life-long immunosuppressive treatment, which may occasionally be associated with life-threatening complications. These complications of long-term immunosuppressive treatment would be avoided if it were possible to achieve a state of antigen-specific unresponsiveness that would promote a condition such tolerance we have attempted to induce such tolerance by injection of donor's spleen cells to recipients spleen at the end of operation and by administration of cyclosporin for only 7 days postoperatively.Mate … More rials and MethodsFirst Research : Male or female pigs weighing from 18 to 22 kg were used. Before induction of ischemic injury to the liver, side-to-side portocaval shunt and cannulation through the common bile duct were performed. Warm ischemia for 3 hours was induced by cross-clamping the portal vein and the hepatic artery at the hepatic hilus. The animals were divided into two groups : Group I pigs (n=7) served as the control, Group II (n=5) was given FK506 (1mg/kg, i. m.) for 4 days prior to being subjected to the ischemia. Survival rate, serum glutamic oxaloacetic transaminase (S-GOT), serum lactic dehydrogenase (S-LDH), hepatic transport activity of BSP, bile flow, neutrophil dependent chemiluminescence, and histologic examination of the liver were serially studied.Second Research : Eleven orthotopic liver transplantations were performed on female young pigs weighing from 14 to 21 kg. The animals were divided into control (4 pigs) and vagotomy (7 pigs) groups. Bilateral truncal vagotomy and phyloroplasty were performed in pigs of vagotomy group. Cyclosporin (10 mg/kg, orally) was given postoperatively in the both groups. A necropsy was performed when recipient pigs died.Third Research : To study the induction of immuno-tolerance, 5 orthotopic liver transplantations with truncal vagotomy and pyloroplasty were performed on female young pigs weighing from 19 to 20 kg. The animals were randomized into control (3 pigs) which received a 7-day postoperative course of cyclosporin (10 mg/kg, orally) and the experimental group which received the injection of donor's spleen cells (2^*10^9) to the recipient spleen via the splenic artery at the end of operation and a 7-day postoperative course of cyclosporin.ResultsFirst Research : Six of 7 animals in Group I (control) died within 7 days. In contrast, all of the 5 pigs in Group II survived more than 7 days. Hepatic transport activity of BSP and bile flow were improved in Group II. The chemiluminescence of blood samples from Group I increased markedly after reperfusion. In contrast, marked increase of the chemiluminescence of blood from Group II was not observed. Vacuolar degeneration of the hepatic cells and dilatation of the sinusoid in Group I were revealed histologically, similar histological changes of the liver in Group II, however, were slight.Second Research : In the control pigs which did not have vagotomy-pyloroplasty, the incidence of the ulcer was 100%. The ulcers involved the cardia-lesser curvature massively and all four animals died of massive gastrointestinal bleeding. In the vagotomy group, gastric ulcer was not observed. One pig is still alive one year after operation. The others died of ileus (two pigs, survived in days 5 and 28), liver necrosis (one pig, 3 days), suppurative cholangitis (2 pigs, in day 34 and 84), accidental bleeding due to falling out from arterial cannulation (one pig, 3 days). Vagotomy-pyloroplasty prevented gastric ulcer very effectively in young pig orthotopic liver transplantation.Third Research : Results of the experiment to induced the immunoto-lerance are not clear yet. Survival of the experimental group which received donor's spleen cells was in days 28 and 84. In contrast, survival of the control group was in days 3, 5 and 34. Less
第一项研究:本实验研究免疫抑制剂FK 506对猪肝热缺血损伤的保护作用,作为肝脏保存的研究。研究之二:幼猪原位肝移植术后溃疡的发生率很高。因此,我们研究了猪肝移植后胃溃疡的发病机制及其预防迷走神经幽门成形术。第三项研究:为了有效地防止排斥反应,同种异体移植受体通常接受终身免疫抑制治疗,这可能偶尔与危及生命的并发症。如果能达到一种抗原特异性无反应状态,促进免疫耐受,就可以避免长期免疫抑制治疗的这些并发症。我们曾试图在手术结束时将供体脾细胞注射到受体脾中,术后仅用7天的环孢菌素来诱导这种耐受。 ...更多信息 方法研究一:选用体重18 ~ 22 kg的公、母猪。在诱导肝脏缺血性损伤之前,进行侧-侧门腔静脉分流术和经胆总管插管。通过在肝门处交叉夹闭门静脉和肝动脉诱导热缺血3小时。实验动物分为两组,Ⅰ组(n=7)为对照组,Ⅱ组(n=5)为FK 506(1 mg/kg,i.米)。在进行局部缺血前4天。对存活率、血清谷草转氨酶(S-GOT)、血清乳酸脱氢酶(S-LDH)、肝内BSP转运活性、胆汁流量、中性粒细胞依赖的化学发光和肝脏组织学检查进行了连续观察。动物分为对照组(4只)和迷走神经切断组(7只)。迷走神经切断组行双侧迷走神经干切断和神经叶成形术。两组术后均给予环孢素10 mg/kg口服。第三项研究:为了研究免疫耐受的诱导,对体重为19 - 20 kg的雌性幼猪进行了5次原位肝移植联合迷走神经干切断术和幽门成形术。将动物随机分为对照组(3只猪),术后接受7天的环孢菌素治疗实验组在手术结束时经脾动脉向受体脾内注射供体脾细胞(2^* 10 ^9),术后给予环孢素7天。第I组(对照组)7只动物中有6只在7天内死亡。相比之下,组II中的所有5头猪均存活超过7天。Ⅱ组肝内BSP转运活性和胆汁流量均得到改善。再灌注后,I组血标本的化学发光明显增强。相比之下,II组血液化学发光未观察到明显增加。第二研究:未行迷走神经切断术-幽门成形术的对照组猪,溃疡发生率为100%。溃疡大量累及心脏小弯,所有四只动物均死于胃肠道大出血。在迷走神经切断组中,未观察到胃溃疡。一只猪在手术后一年还活着。其他动物死于肠梗阻(2只猪,在第5天和第28天存活)、肝坏死(1只猪,3天)、化脓性胆管炎(2只猪,在第34天和第84天)、由于动脉插管脱落导致的意外出血(1只猪,3天)。迷走神经幽门成形术在幼猪原位肝移植中能有效地预防胃溃疡的发生。研究之三:诱导免疫耐受的实验结果尚不清楚。接受供体脾细胞的实验组的存活时间为28天和84天。相比之下,对照组的存活时间为第3、5和34天。少
项目成果
期刊论文数量(26)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Kazufumi Okamoto共著: "Intraoperative management of a patient undergoing extracoporeal Ilver surgery (bench surgery)" Journal of Anesthesia. 5. 436-440 (1991)
Kazufumi Okamoto 合着:“接受体外 Ilver 手术(台式手术)的患者的术中管理”《麻醉杂志》5. 436-440 (1991)。
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沢田 俊彦(共著): "ブタ同所性肝移植術ーVーV bypassの門脈の流出路にドナ-下大静脈片を使用する新術式" 今日の移植. (1991)
Toshihiko Sawada(合著者):“猪原位肝移植 - 在 V-V 旁路的门静脉流出道中使用供体下腔静脉碎片的新手术技术”今日移植(1991 年)
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Shunji Kawamoto 共著: "Mechanism for enteroーhepatic injury caused by circulatory disturbance of hepatic vessel in the rat" proc.Soc.Exp Bio1.Med. 198. 629-635 (1991)
Shunji Kawamoto 合着:“大鼠肝血管循环障碍引起的肠肝损伤的机制” proc.Soc.Exp Bio1.Med 198. 629-635 (1991)
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Sawada T, Tashiro S, Inoue K, Kawamoto S, Tsuji T, Tanabe D, Kanemitsu K, Kamimoto Y.: "A technique of orthotopic liver transplantation by veno-venous bypass using donor's caval graft as a shunt route from the portal vein in the pig." Trnasplantation Now.
Sawada T、Tashiro S、Inoue K、Kawamoto S、Tsuji T、Tanabe D、Kanemitsu K、Kamimoto Y.:“一种通过静脉-静脉旁路进行原位肝移植的技术,使用供者的腔静脉移植物作为门静脉的分流路线
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田代 征記 他: "体外肝手術による肝左三区域切除・右肝静脈部分記除術の経験" 手術. 45. 507-514 (1991)
Masaki Tashiro 等:“体外肝脏手术左三段切除和右肝静脉部分切除的经验”Surgery 45. 507-514 (1991)。
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