Restoration of renal microcirculation by eNOS gene transfection for overcoming the antibody-mediated rejection and achievement of long-term renal allograft survival

通过eNOS基因转染恢复肾微循环以克服抗体介导的排斥反应并实现肾同种异体移植物的长期存活

• 批准号: 15390487
• 负责人: TAKAHASHI Kota
• 金额: $ 8万
• 依托单位: Niigata University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-15390487/
• 关键词: microcirculation injury; ischemia-reperfusion injury; renal vascular endothelial cells; rat bone marrow transplantation; GFP positive cells; stem cell transplantation; 腎虚血再潅流生涯; 血管内皮細胞傷害; GFPラット; 実時間型実体顕微鏡; シクロスポリン; アデノウイルスベクター; 腎虚血再灌流障害; 血管内

1. From the clinicopathological observation of antibody-mediated rejection in living donor ABO-incompatible kidney transplantation and ischemia-reperfusion injury in deceased donor kidney transplantation, We had analyzed and evaluated the process of the microcirculation injury and microvascular endothelial cell damage.2. We had established the GFP(+) to (-) rat bone marrow transplantation model and evaluated the role of The bone marrow derived endothelial progenitor cells in the regeneration of the injured microvascular Cells in renal ischemia-reperfusion injury.3. We have revealed that the bone marrow derived endothelial cells have migrated and recovered the injured endothelial cells in renal ischemia-reperfusion injury.It was approved not only by static immunohinstopathological method but also by dynamic direct observation by real-time phase contrast microscopy.4. We have also established in vitro eNOS gene transfection into cultured vascular endothelial cells, However, transplantation and restoration of injured endothelial cells by eNOS transfectant endothelial cells in "in vivo" experimental model could not be established.5.These result will be useful for the clinical renal preservation and regeneration therapy for antibody-mediated rejection in ABO-incompatible kidney transplantation and ischemia-reperfusion injury in deceased donor kidney transplantation.

1.通过对活体供者ABO血型不合肾移植中抗体介导的排斥反应和已故供者肾移植中缺血再灌注损伤的临床病理观察，分析和评价微循环损伤和微血管内皮细胞损伤的过程。建立GFP（+）转GFP（-）大鼠骨髓移植模型，评价骨髓源性内皮祖细胞在肾缺血再灌注损伤中对受损微血管细胞再生的作用.本研究揭示了骨髓来源的内皮细胞在肾缺血再灌注损伤中迁移并修复受损的内皮细胞，这不仅得到了静态免疫组织病理学方法的证实，而且得到了实时相差显微镜动态直接观察的证实.我们还建立了体外eNOS基因转染培养的血管内皮细胞，然而，本实验结果为临床上ABO血型不合肾移植和缺血性肾损伤的保护和再生治疗提供了实验依据。死亡供体肾移植再灌注损伤的研究

项目成果

Bone marrow cells contribute to damaged glomerular endothelial cells

骨髓细胞导致肾小球内皮细胞受损

• 发表时间: 2005
• 期刊: Kidney International 67(5)
• 作者: Ikarashi K;Li B;Suwa M;et al.
• 通讯作者: et al.

Local deliveryof angiotensin receptor blocker into the kidney ameliorates progression of experimental glomerulonephritis.

将血管紧张素受体阻滞剂局部递送至肾脏可改善实验性肾小球肾炎的进展。

• 发表时间: 2006
• 期刊: Kidney International 70
• 作者: J.Mahmood;F.Khan;S.Okada;N.Kumagai;T.Morioka;T.Oite
• 通讯作者: T.Oite

諏訪通博: "実時間型共焦点レーザー走査生体顕微鏡を用いたEnhanced Green Fluorescent Protein(EGFP)陽性細胞の同定法"新潟医学会雑誌. 118・12(印刷中). (2004)

Michihiro Suwa：“使用实时共聚焦激光扫描生物显微镜识别增强型绿色荧光蛋白 (EGFP) 阳性细胞”，《新泻医学会杂志》118, 12（出版中）。

Local delivery of angiotensin receptor blocker into the kidney ameliorates progression of experimental glomerulonephritis.

将血管紧张素受体阻滞剂局部递送至肾脏可改善实验性肾小球肾炎的进展。

• 发表时间: 2006
• 期刊: Kidney International 70
• 作者: J.Mahmood;F.Khan;S.Okada;N.Kumagai;T.Morioka T.Oite.
• 通讯作者: T.Morioka T.Oite.

Kawamura K, Li B, Suwa M, et al.: "Turbulence of glomerular hemodynamics involved in the progressive glomerulosclerosis"Journal of American Society of Nephrology. 14. 605A (2003)

Kawamura K、Li B、Suwa M 等人：“进行性肾小球硬化症中涉及的肾小球血流动力学湍流”美国肾脏病学会杂志。