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.

这项研究的目的是可视化肾小球微循环中传播血管内凝血（DIC）的过渡，并通过将血液流量速度测量为大鼠的指数来评估肝素和血小板激活因子CV3988的抑制剂CV3988。为了影响DIC，将5mg/kg的脂多糖（LPS）静脉注射到Wistar大鼠。使用我们的CCD插入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。诱导的DIC，导致肾小球毛细血管血流速度的降低。在诱导DIC之前对肝素进行预处理，可防止血流速度降低约10％。在诱导DIC之前对CV3988进行预处理，可防止血流速度降低90％。用肝素和CV3988预处理完全消除了血流速度下降。无诱导DIC的肝素或CV3988的唯一给药根本不会引起任何血流速度变化。 CV3988比肝素更有效，对于血流速度降低。发现CV3988和肝素的预处理可防止DIC从血流速度的方面进展。这种组合治疗预计将是针对DIC的新方法。

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。

Yasuo Ogasawara: "Three-dimensional quantitative analysis of glomerular microcirculation in diabetic nephropathy using syncrotron radiation X-ray micro-CT"Circulation Journal. 66. 364 (2002)

Yasuo Ogasawara：“利用同步辐射X射线显微CT对糖尿病肾病肾小球微循环进行三维定量分析”循环杂志。