Real-time observation of glomerular hemodynamic changes in diabetic rats: effects of insulin and ARB.
Real-time observation of glomerular hemodynamic changes in diabetic rats: effects of insulin and ARB.
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DOI：
10.1111/j.1523-1755.2004.00979.x
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发表时间：
2004-11
影响因子：
19.6
通讯作者：
Bing Li;Jian Yao;K. Kawamura;Y. Oyanagi-Tanaka;M. Hoshiyama;T. Morioka;F. Gejyo;M. Uchiyama;T. Oite
中科院分区：
文献类型：
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作者：
Bing Li;Jian Yao;K. Kawamura;Y. Oyanagi-Tanaka;M. Hoshiyama;T. Morioka;F. Gejyo;M. Uchiyama;T. Oite
背景糖尿病肾病的进展与肾小球血流动力学紊乱密切相关，如肾小球高血压和/或高灌注。应用激光共聚焦扫描显微镜（CLSM）观察和分析糖尿病（DM）大鼠肾小球血流动力学。我们还研究了坎地沙坦酯（TCV-116），一种选择性血管紧张素II 1型受体阻滞剂（ARB），对糖尿病肾小球血流动力学的影响。方法将Munich-Wistar大鼠分为6组：（1）4 d对照组;（2）4 d糖尿病组;（3）28 d对照组;（4）28 d糖尿病组;（5）糖尿病胰岛素治疗组;（6）糖尿病TCV-116治疗组。估计肾体重比、肾小球体积和蛋白尿。采用激光共聚焦显微镜观察肾小球血流动力学变化，免疫荧光法检测肾组织内皮型一氧化氮合酶（eNOS）和神经型一氧化氮合酶（nNOS）的表达。结果糖尿病4 d组大鼠肾重/体重比、肾小球体积、输入小动脉（AA）和输出小动脉（EA）直径、肾小球内红细胞流速和肾小球毛细血管袢体积流量均显著高于对照组，糖尿病28 d组增加更为明显。TCV-116治疗改善了所有这些结果，并显著降低了蛋白尿，但对血糖水平没有影响。另一方面，胰岛素治疗后，所有这些变化的正常化引起的糖尿病。当用TCV-116或胰岛素治疗时，DM中增强的肾脏eNOS表达被抑制，而四组中nNOS的表达没有改变。结论该成像方法可用于评价肾小球微循环，包括AA和EA直径、红细胞流速和体积流量。糖尿病可引起肾小球血流动力学改变和肾脏肥大。糖尿病治疗与胰岛素或ARB改善这些变化。这项研究表明，成像技术的进步有望为揭示肾小球疾病中血流动力学变化的参与，帮助预后和监测治疗效果做出重大贡献。
BACKGROUND The progression of diabetic nephropathy is closely related to disturbances in glomerular hemodynamics, such as glomerular hypertension and/or hyperperfusion. The aim of this study was to observe and to analyze glomerular hemodynamics in rats with diabetes mellitus (DM) in vivo using confocal laser scan microscopy (CLSM). We also examined the effects of candesartan cilexetil (TCV-116), a selective angiotensin II type 1 receptor blocker (ARB), on glomerular hemodynamics in DM. METHODS Munich-Wistar rats were divided into six groups: (1) four-day control; (2) four-day DM; (3) 28-day control; (4) 28-day DM; (5) DM treated with insulin; (6) DM treated with TCV-116. The kidney-to-body weight ratio, glomerular volume, and proteinuria were estimated. Glomerular hemodynamic changes were observed using CLSM and renal expression of endothelial nitric oxide synthase (eNOS), and neuronal nitric oxide synthase (nNOS) was evaluated by immunofluorescence. RESULTS The kidney-to-body weight ratio, glomerular volume, the diameters of afferent arterioles (AA) and efferent arterioles (EA), erythrocyte velocities within glomeruli, and volume flow in glomerular capillary loops in four-day DM were significantly higher than in control rats, and increases were even more pronounced in the 28-day DM. TCV-116 treatment ameliorated all these findings and significantly decreased proteinuria, but there was no effect on the blood glucose level. On the other hand, insulin treatment was followed by normalization of all these changes induced in DM. Enhanced renal expression of eNOS in DM was suppressed when treated with either TCV-116 or insulin, while expression of nNOS was unaltered among the four groups. CONCLUSION This imaging procedure allowed us to evaluate glomerular microcirculation in vivo, including the diameters of AA and EA, erythrocyte velocity, and volume flow. DM significantly induced glomerular hemodynamic alteration and renal hypertrophy. DM treated with either insulin or ARB ameliorated these changes. This study shows that progress in imaging technology promises to make major contributions to revealing the involvement of hemodynamic changes in glomerular diseases, aiding prognosis and the monitoring of therapeutic effects, as well.