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

本研究的目的是可视化肾小球微循环中弥散性血管内凝血（DIC）的转变，并通过测量大鼠的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。Wistar大鼠静脉注射5mg/kg脂多糖（LPS）诱导DIC。采用空间分辨率为0.86μm、时间分辨率为33ms的CCD活体视频显微镜系统测量肾小球毛细血管血流速度。LPS诱导DIC，导致肾小球毛细血管血流速度降低。在DIC诱导前用肝素预处理可防止血流速度下降约10%。在DIC诱导前用CV3988进行预处理，可使血流速度降低90%。肝素和CV3988预处理完全消除血流速度下降。单独给药肝素或CV3988均未引起DIC，没有引起血流速度的变化。CV3988对血流速度的降低比肝素更有效。从血流速度方面发现CV3988和肝素预处理均可阻止DIC的进展。这种联合治疗有望成为治疗DIC的一种新方法。

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.