Pathogesis and prevention of graft rejection and graft coronary arteriosclerosis in an experimental heart transplantation model

实验性心脏移植模型中移植物排斥反应和移植物冠状动脉硬化的发病机制及预防

• 批准号: 03670651
• 负责人: TABAYASHI Koichi
• 金额: $ 1.28万
• 依托单位: TOHOKU UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1991
• 资助国家: 日本
• 起止时间: 1991 至 1993
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-03670651/
• 关键词: working model; non-working model; coronary arteriosclerosis; graft rejection; graft coronary arteriosclerosis; workingモデル; 急性拒絶反応; 慢性拒絶反応; PGI_2; non-working model; working model; 冠動脈病変; 心臓移植; 冠動脈硬化; シクロスポリン; FK506; 15ーDeoxyspergualin

The purpose of this study are to evaluate the effects of immunosuppressivedrugs, to compare the effects of non-working left heart model and working model, and to assess the protective effects of PG12 on myocardial rejection and coronary arteriosclerosis after heterotopic heart transplantation.1)Comparison of the effects of Cyclosporine(Cs), FK-506(FK) and 15-Deoxyspergualin(DOS) on coronary arteriosclerosis after rat heart transplantation.Three gruops of Lewis rats(n=7, each)received heterotopic heart transplants from F-344 donors and were treated with Cs, FK, and DOS intraperitoneally.All rats were sacrificed 60 days after transplantation and assessed microscopic grading asore of rejection and arteriosclerosis, andmeasured serum lipid.There was no significant difference in the grading score of arteriosclerosis in the Cs group was significantly higher than it of DOS group.Trigriceride level in the Cs group was significantly higher than the FK and DOS groups, and LOL level in the Cs and … More FK groups were significantly higher than them of DOS group. We conclude that DOS has a superior protective effect against coronary arteriosclerosis after heart transplantation and it may depend on the different mechanizm of immunosuppression and lipid metabolism abnormality causing by immunosuppressants.2)Technique for working left heart model of heterotopic(abdominal)heart transplantation.The interatrial septum and tricuspid valve of the donor heart are removed. The pulmonary arterial trunk, pulmonary veins, and inferior vena cava are ligated, and the stumps of the donor aorta and superior vena cava are anastomosed in an end-to-side fashion to the recipient abdominal aorta and inferior vena cava, respectively. In this model, the donor left ventricle did not pump out enough venous blood to desaturate the recipient femoral arterial blood but did generate approximately the same pressure as the recipient's heart.3)Comparison of the effects of non-working left heart model and working model, and the protection effects of prostaglandin 12(PG12) on graft rejection and graft coronary arterisclerosis after heterotopic heart transplantation.Fischer rats were used as donors and Lewis rats as recipients.Twenty Fischer to Lewis allograft were diveded equally into six groups.Group 1 received working type of heterotopic heart transplantation without treatment of cychosporin A (Cy A) and PG12, and killed on day 20.Group 2 received non-working type of heterotopic heart transplantation without treatment of Cy A and PG12, and killed on day 20.Group 3 received working type of heterotopic heart transplantation with treatment of CY a and without PG12, and killed on day 60.Group 4 received non-working type of heterotopic heart transplantation with treatment of Cy a and without PG12, and killed on day 60.Group 5 received working type of heterotopic heart transplantation with treatment of Cy A and PG12, and killed on day 60.Group 6 received non-working type of heterotopic heart transplantation with treatment of Cy A and PG12, and killed on day 60.The severity of rejection was evaluated using Billingham grading scale.The degree of coronary arterial injury was assessed using Lurie grading scale.Left ventricular wall theckness was measured at the free wall and interventricular septum. The following results were obtained.i)LV free wall thickness of graft in working model was significantly thicker than it in recipient heart.LV wall thickness of grafts in non-working model was the same as it in recipient heart.ii)The degree of rejection in working model was the same as it in non-working model.iii)The degree of coronary arterial injury in working model was significantly lesser than it in non-working model.iv)There was no significant difference of the degree of rejection with or without treatment of PG12.v)There was no significant difference of the degree of graft coronary arteriosclerosis with or without treatment of PG12. Less

本研究的目的是评价免疫抑制剂对异位心脏移植术后心肌排斥反应和冠状动脉粥样硬化的影响，比较非工作模型和工作模型的效果，以及PG_（12）对异位心脏移植术后心肌排斥反应和冠状动脉粥样硬化的保护作用。FK-506和15-脱氧精胍菌素对大鼠心脏移植后冠状动脉粥样硬化的影响（n=7，各）接受来自F-344供体的异位心脏移植，并用Cs，FK，所有大鼠于移植后60天处死，进行排斥反应和动脉硬化的显微镜分级，Cs组动脉硬化分级评分明显高于DOS组，Cs组甘油三酯水平明显高于FK组和DOS组，Cs组和DOS组的LOL水平明显高于FK组和DOS组，Cs组和DOS组的LOL水平明显高于FK组和DOS组，Cs组和DOS组的LOL水平明显高于FK组和DOS组。 ...更多信息 FK组明显高于DOS组。结论：DOS对心脏移植术后冠状动脉粥样硬化有上级保护作用，其机制可能与免疫抑制剂引起的免疫抑制和脂代谢异常有关。2）异位（腹式）心脏移植左心模型制作技术：去除供心的房间隔和三尖瓣。结扎肺动脉干、肺静脉和下腔静脉，并将供体主动脉和上级腔静脉的残端以端侧方式分别与受体腹主动脉和下腔静脉吻合。在该模型中，供体左心室没有泵出足够的静脉血来使受体股动脉血液去饱和，但确实产生了与受体心脏大致相同的压力。3）非工作左心模型和工作模型的效果比较，前列腺素12（PG 12）的保护作用以Fischer大鼠为供体，刘易斯大鼠为受体，将20只Fischer-刘易斯同种异体心脏平均分为6只第1组为工作型异位心脏移植组，术后第20天处死;第2组为非工作型异位心脏移植组，术后第20天处死;第3组为工作型异位心脏移植组，术后第20天处死;第4组为非工作型异位心脏移植组，术后第60天处死;第5组为工作型异位心脏移植组，术后第60天处死。第6组为非工作型异位心脏移植组，给予Cy A和PG 12治疗，采用比灵厄姆分级法评价排斥反应的严重程度，Lurie分级法评价冠状动脉损伤程度，测量左室游离壁和室间隔厚度。结果表明：工作模型移植物左室游离壁厚度明显大于受体心脏，非工作模型移植物左室游离壁厚度与受体心脏相同;工作模型移植物排异反应程度与非工作模型相同;工作模型冠状动脉损伤程度明显小于非工作模型;有或没有PG 12治疗的排斥反应的程度没有显着差异。v）有或没有PG 12治疗的移植物冠状动脉硬化的程度没有显着差异。少

项目成果

Ohmi M,Yokoyama H,Nakame T,et al: "Hemodynamic performance in a heterotopically transplanted dog heart:Roposal of techniques for working left heart model of heterotopic(abdominal)heart transplantation." J.Heart.Lung.Transplant.11. 1147-1150 (1992)

Ohmi M、Yokoyama H、Nakame T 等人：“异位移植狗心脏的血流动力学表现：异位（腹部）心脏移植左心模型技术的建议”。

Ohmi M, Yokoyama II,Nakame T. et al: "Hemodynamic performance in a heterotopically transplanted Dog heart: Proposal of techniques for working left heart model of he terotopic(abdominal) heart transplantation" J Heart Lung transplant. 11. 1147-1150 (1992)

Ohmi M、Yokoyama II、Nakame T. 等人：“异位移植狗心脏的血流动力学性能：异位（腹部）心脏移植的左心模型工作技术的建议”J心肺移植。

長嶺 進: "心移植後の冠動脈硬化に関する実験的研究ー特に免疫抑制剤の影響についてー" 日本胸部外科学会雑誌.

Susumu Nagamine：“心脏移植后冠状动脉硬化的实验研究 - 特别是免疫抑制剂的影响”日本胸外科学会杂志。