Development of new preservation solution to maintain vascular endothelial Integlity.

开发新的保存液以维持血管内皮完整性。

• 批准号: 13557101
• 负责人: JIN Maeng bong
• 金额: $ 8.7万
• 依托单位: HOKKAIDO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13557101/
• 关键词: Rho; Y-27632; edaravone; HTK; NAG; Cr; FENa; MDA; ET-1; 尿中NAG; HTK液; Rho-Kinase; 肝温阻血障害; ICAM-1; アデノシン; サイクリックAMP; アデニレートサイクラーゼ; ホスホジエステラーゼIII; アムリノン; ミルリノン; オロプリノン

A. The effect of vaso-reactive substances on the organ preservation were investigated. Vaso-active substances could reduce neutrophil infiltration into reperfused liver tissue. They also promoted the maintenance of hepatic tissue blood flow even after 2hr complete hepatic warm ischemia using total hepatic vascular occlusion model. Moreover, they attempted remarkable recovery of hepatic energy metabolism.B. For example, we tried a brand new Rho-associated protein kinase, Y 27632 to prove that Rho-kinase can play a key role even in the hepatic ischemia reperfusion injury. Male SD rats were engaged in a 70% partial hepatic ischemia model. Animals were divided into two groups, a no-treated group, a group treated with 10mg/kg Y-27632 p.o before 90 min warm ischemia, Survival, arterial pressure, hart rate, hepatic tissue blood flow, ALT, ET-1, Hyauronic acid, MPO activity, Mac-1 stain, and pathological history were investigated. The treatment ameliorated survival, hepatic tissue blood flow, ALT, ET-1, HA, and MPO, significantly, and also reduced the number of Mac-1 positive neutrophil infiltration into liver tissue.C. A brand new substance, edaravone, was tested for its ability as a radical scavenger using canine kidney auto transplantation model after 72hr cold preservation in HTK solution. Animal were randomly divided into two groups, treated one and untreated control. Edaravone was infused systematically before graft procurment, given into preservation solution, and administered systematically after grafting. The treatment unproved urine volume, NAG/Cr, FENa, and lessened Cr level, acute tubular necrosis, and MDA level in kidney draft.

A.探讨血管反应性物质在器官保存中的作用。血管活性物质可减少中性粒细胞向再灌注肝组织的浸润。它们还促进了肝组织血流的维持，即使在使用全肝血管闭塞模型的2小时完全肝热缺血后。此外，他们还试图显著恢复肝脏的能量代谢。例如，我们尝试了一种新的Rho相关蛋白激酶Y 27632，以证明Rho激酶在肝脏缺血再灌注损伤中也能发挥关键作用。雄性SD大鼠采用70%部分肝缺血模型。实验动物分为两组，热缺血前90 min给予Y-27632（10 mg/kg），观察动物存活率、动脉压、哈特率、肝组织血流量、ALT、ET-1、透明质酸、MPO活性、Mac-1染色及病理学变化。治疗组的生存率、肝组织血流量、ALT、ET-1、HA和MPO均明显改善，Mac-1阳性中性粒细胞浸润肝组织的数量也明显减少。用HTK液冷保存72小时的犬自体肾移植模型，检测了一种新物质依达拉奉作为自由基清除剂的能力。将动物随机分为两组，治疗组和未治疗对照组。依达拉奉在移植前系统输注，保存液中加入依达拉奉，移植后系统给药。治疗组尿量、NAG/Cr、FENa明显增加，Cr水平、急性肾小管坏死、肾功能指标MDA水平明显降低。

项目成果

Takeda T, Jin MB, Fujita M, Sakurai T, Nakayama M, Taniguchi M, Suzuki T, Shimamura T, Furukawa H, Todo S.: "A novel inhibitor of Rho-associated protein kinase, Y-27632, ameliorates hepatic ischemia and reperfusion injury in rats"Surgery. 133. 197-206 (20

Takeda T、Jin MB、Fujita M、Sakurai T、Nakayama M、Taniguchi M、Suzuki T、Shimamura T、Furukawa H、Todo S.：“Rho 相关蛋白激酶的新型抑制剂 Y-27632 可改善肝缺血和

Jin MB, et al.: "Clinical path in liver transplantation"Clinical Surgery (in Japanese). 58(11). 144-150 (2003)

Jin MB等：《肝移植的临床路径》《临床外科》（日文）。

Ishikawa H.: "Elevation of cyclic nucleotides attenuates ischemia and reperfusion injury of liver"Transplantation Proceedings. 33(1-2). 982-983 (2001)

Ishikawa H.：“环核苷酸的升高可减轻肝脏的缺血和再灌注损伤”移植论文集。

Masuko H, Jin MB, Horiuchi H, Suzuki T, Taniguchi M, Shimamura T, Fukai M, Magata S, Ogata K, Ishikawa H, Fujita M, Nagashima K, Furukawa H, Todo S: "Protective effect of angiotensin type I receptor antagonist, CV-11974, on ischemia and reperfusion injury

Masuko H、Jin MB、Horiuchi H、Suzuki T、Taniguchi M、Shimamura T、Fukai M、Magata S、Ogata K、Ishikawa H、Fujita M、Nagashima K、Furukawa H、Todo S：“血管紧张素 I 型受体的保护作用

Jin MB: "Manual for organ transplantation in animal experiment"Nihonigakukan, Tokyo. (2003)

Jin MB：“动物实验器官移植手册”，东京日本学院。