Construction of an analysis system on acute renal failure pathogenesis by direct measurement of renal microcirculation haemodynamics

直接测量肾脏微循环血流动力学分析急性肾衰竭发病机制的构建

• 批准号: 14380418
• 负责人: NAKAMOTO Hiroshi
• 金额: $ 9.09万
• 依托单位: Kawasaki Medical School
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14380418/
• 关键词: microcirculation; visualisation; CCD intravital videomicroscope; acute renal failure; blood flow velocity; endotoxin; glomerulus; disseminated intravascular coagulation; 播種性血管内

The purposes of this study are to visualise the transition of disseminated intravascular coagulation(DIC) in the glomerular microcirculation and to evaluate the effects of heparin and an inhibitor of platelet activating factor, CV3988, by measuring blood flow velocity as an index in a rat. To induce DIC, 5mg/kg of lipopolysaccharide(LPS) was administered intravenously to Wistar rats. Glomerular capillary blood flow velocities were measured with our CCD intravital videomicroscope system, which has a spatial resolution of 0.86μm and a time resolution of 33ms.LPS induced DIC resulting in decrease of glomerular capillary blood flow velocities. Pretreatment with heparin before induction of DIC prevented blood flow velocity decrease approximately by 10%. Pretreatment with CV3988 before induction of DIC prevented blood flow velocity decrease by 90%. Pretreatment with heparin and CV3988 completely abolished the blood flow velocity decrease. Sole administration of either heparin or CV3988 without inducing DIC did not cause any blood flow velocity change at all. CV3988 was more effective than heparin for the blood flow velocity decrease. The pretreatment with both CV3988 and heparin was found to prevent progression of DIC from the aspect of blood flow velocity. This combination treatment is expected to be a new treatment against DIC.

本研究的目的是观察肾小球微循环中弥散性血管内凝血 (DIC) 的转变，并通过测量大鼠血流速度作为指标来评估肝素和血小板活化因子抑制剂 CV3988 的作用。为了诱导DIC，给Wistar大鼠静脉注射5mg/kg的脂多糖(LPS)。采用我们的CCD活体视频显微镜系统测量肾小球毛细血管血流速度，该系统的空间分辨率为0.86μm，时间分辨率为33ms。LPS诱导DIC导致肾小球毛细血管血流速度降低。在诱导 DIC 之前用肝素进行预处理可防止血流速度降低约 10%。在诱导 DIC 之前用 CV3988 进行预处理可防止血流速度降低 90%。肝素和CV3988预处理完全消除了血流速度的降低。单独施用肝素或 CV3988 而不诱导 DIC 根本不会引起任何血流速度变化。 CV3988对于降低血流速度比肝素更有效。研究发现，CV3988和肝素联合预处理可从血流速度方面预防DIC的进展。这种联合治疗有望成为对抗DIC的新疗法。

项目成果

Tokunori Yamamoto: "Visualisation of in-vivo renal microcirculation in hypertensive and diabetic pathological rat models"Journal of Japanese Society of Biorheology(B & R). 16(4). 91-100 (2002)

山本德典：“高血压和糖尿病病理大鼠模型体内肾脏微循环的可视化”日本生物流变学会杂志（B）

Takahiko Kiyooka: "Functional role of capillaries in reactive hyperemia by direct observation with a pencil-lens intravital videomicroscope"Microcirculation annual 2003. 19. 63-64 (2003)

Takahiko Kiyooka：“通过使用铅笔镜头活体视频显微镜直接观察毛细血管在反应性充血中的功能作用”微循环年鉴 2003. 19. 63-64 (2003)

Takahiko Kiyooka: "Functional role of capillaries in reactive hyperemia by direct observation with a pencil-lens intravital videomicroscope"Microcirculation annual. 19. 63-64 (2003)

Takahiko Kiyooka：“通过使用铅笔式活体视频显微镜直接观察毛细血管在反应性充血中的功能作用”年度微循环。

Yasuo Ogasawara et al.: "Analysis of three dimensional architecture of reanl microcirculation"SPring-8 User Experiment Report. 9. 125 (2002)

Yasuo Ogasawara等人：《真实微循环三维架构分析》SPring-8用户实验报告。

Hiroshi Nakamoto: "In-vivo Evaluation of renal microcirculatiory disturbance -by glomerular capillary blood flow velocity measurement-"6th Polish-Japanese Symposium on Bio-Medical Engineering. 47-51 (2003)

Hiroshi Nakamoto：“肾脏微循环障碍的体内评估 - 通过肾小球毛细血管血流速度测量 -”第六届波兰-日本生物医学工程研讨会。