Boyce N W, Holdsworth S R
Kidney Int. 1987 Jan;31(1):8-14. doi: 10.1038/ki.1987.2.
An isolated perfused kidney system (IPK) was used to study the direct intrarenal hemodynamic effects of binding of anti-glomerular-basement membrane (anti-GBM) antibody in the absence of all other circulating humoral and cellular inflammatory mediators. Control IPK's (perfused with Krebs-Henseleit buffered 5% albumin solution containing non-immune globulin) had a renal vascular resistance (RVR) mean +/- SEM 3.10 +/- 0.47 mm Hg/ml/min and a GFR mean +/- SEM 0.63 +/- 0.8 ml/min/g. Anti-GBM antibody administration raised RVR (4.83 +/- 0.52 mm Hg/ml/min, P less than 0.01) and lowered GFR (0.34 +/- 0.04 ml/min/g, P less than 0.01). Perfusate renin activity was higher after antibody administration (684 +/- 87 ng AI/ml/hr compared with control 308 +/- 42 ngAI/ml/hr, P less than 0.01). Treatment with Sar1Ala8All (3 X 10(-6) M) or captopril (10 mg/ml) attenuated antibody-induced vasoconstriction (RVR mm Hg/ml/min, Sara1Ala8All = 3.78 +/- 0.13 captopril = 3.26 +/- 0.12, both P less than 0.05 compared with anti-GBM alone). Both inhibitors of the renin-angiotensin system (RAS) also aggrevated the decline in GFR seen after antibody administration (GFR ml/min/g, Sara1Ala8All = 0.24 +/- 0.05, Captopril = 0.18 +/- 0.03, both P less than 0.05 compared with anti-GBM alone). These IPK studies demonstrate that anti-GBM antibody itself may directly induce intrarenal hemodynamic alterations in the absence of complement activation, neutrophil infiltration, neural influences or circulating vasoactive substances. The results from perfusate renin sampling and blockade of the RAS provide evidence that anti-GBM antibody deposition activates the intrarenal RAS and thereby induces significant hemodynamic alterations.
采用离体灌注肾系统（IPK），在不存在所有其他循环体液和细胞炎症介质的情况下，研究抗肾小球基底膜（anti - GBM）抗体结合的直接肾内血流动力学效应。对照IPK（用含非免疫球蛋白的克雷布斯 - 亨泽莱特缓冲5%白蛋白溶液灌注）的肾血管阻力（RVR）平均值±标准误为3.10±0.47 mmHg/ml/min，肾小球滤过率（GFR）平均值±标准误为0.63±0.8 ml/min/g。给予抗GBM抗体后，RVR升高（4.83±0.52 mmHg/ml/min，P<0.01），GFR降低（0.34±0.04 ml/min/g，P<0.01）。给予抗体后灌注液肾素活性升高（684±87 ng AI/ml/hr，而对照为308±42 ngAI/ml/hr，P<0.01）。用Sar1Ala8All（3×10⁻⁶ M）或卡托普利（10 mg/ml）治疗可减轻抗体诱导的血管收缩（RVR mmHg/ml/min，Sar1Ala8All = 3.78±0.13，卡托普利 = 3.26±0.12，与单独使用抗GBM相比，两者P均<0.05）。肾素 - 血管紧张素系统（RAS）的两种抑制剂也加重了给予抗体后出现的GFR下降（GFR ml/min/g，Sar1Ala8All = 0.24±0.05，卡托普利 = 0.18±0.03，与单独使用抗GBM相比，两者P均<0.05）。这些IPK研究表明，抗GBM抗体本身在不存在补体激活、中性粒细胞浸润、神经影响或循环血管活性物质的情况下，可能直接诱导肾内血流动力学改变。灌注液肾素采样和RAS阻断的结果提供了证据，表明抗GBM抗体沉积激活肾内RAS，从而诱导显著的血流动力学改变。
