肾局部血流在蛋白尿产生中的机制初探

The role of renal cortical blood flow in the development of proteinuria

目的 了解肾局部血流在蛋白尿发生发展过程中的变化及产生机制。方法 ①一次性注射法复制大鼠阿霉素肾病综合征模型。并测取 2 4h尿蛋白含量 ;②分别于蛋白尿的前期、上升期、高峰期及下降期和多功能监护仪测量血压变化 ,激光多普勒微血管流量测定仪测定肾皮质血流 ;③取血及肾皮质匀浆用放射免疫法检测内皮素 (ET)含量 ,用Griess法检测一氧化氮 (NO)代谢产物NO-2 ,代表NO水平 ;④分别研究肾皮质血流与血浆、肾皮质的ET、NO、尿蛋白排泌量的变化及相关性。结果 ①平均动脉压 (mmHg)正常鼠 4个时间点数值为 118,119,118,117;肾病鼠为 116 ,12 4,12 9,12 1;各时间点与同期正常鼠间差异无显著性 ;②肾局部血流量 (Pu) :正常鼠 4个时间点值为 6 6 2 ,6 8 4,6 7 2 ,70 ;肾病鼠为 5 8,5 2 ,19 ,2 3 ;同期比较 :4d差异无显著性 ,8,32 ,5 6d明显低于正常组 ;同组比较 :4,8d分别与 32 ,5 6d差异有显著性 ,4d与 8,32与 5 6d差异无显著性 ;③ 4个时间点血浆ET值 (ng/ml)分别为 134,15 0 ,5 38,445 ,自上升期始明显高于同期对照组 (12 6～12 9) ;肾皮质ET分别为 346 6 ,6 5 3 3 ,15 2 6 8,1393 6 ,自蛋白尿前期 ,均明显高于对照组 (2 35 9～ 2 46 1,P <0 0 5 ) ;4个病期血浆NO值 (nmol/ml)分别为 40 ,36 。

Objective To study the role of renal cortical blood flow (RCBF) in development of proteinuria in rat.Methods ①Neophrotic syndrome was induced by single injection of adriamycin in rat; ②Urinary protein excretion was quantitated every 24 hours; ③Rat blood pressure was measured by multi-function monitor and renal cortical blood flow was measured by multi-function monitor and renal cortical blood flow was neasured by laser-doppler specnoscopy respectively on day 4, 8, 32 and 56 after adriamycin injection; ④Endothelin (ET) and nitric oxide (NO) in rat plasma and renal cortical homogenate were measured by radioimmunoassay and by Griess's method; ⑤The correlation between RCBF and urinary protein, ET or NO was compared respectively. Results ①Urinary protein was normal 4 days after adriamycin injection, increased on day 8; peaked on day 32 and decrease on day 56; ②The arterial blood pressure of the 4 time points was 118, 119, 118 and 117 mmHg in normal rat and was 116, 124, 129 and 121 mmHg in nephrotic rat. There was no difference between nephrotic and normal rat ( P <0 05);③RCBF of the 4 time points was 66,68,67 and 70 in control and was 58, 52,19 and 23 in nephrotic rat, with significant difference between the two group at all time point; ④ET of the 4 time points in nephrotic rat was 134, 150,538 and 445 ng/ml, with significant increase on day 32 and 56 compared to control ( P <0 05). The renal cortical ET of the 4 time points were 365, 653, 1 527 and 1 394, significantly higher than that of corresponding time points in control ( P <0 05);⑤Plasma NO in nephrotic rat was 40, 36, 8 and 11 nmol/ml, significantly lower than that of control from day 32 to day 56. The NO of renal cortex was significantly lower than that of normal rat ( P <0 05).There was no correlation between artery blood pressure and RCBF or urinary protein. Conclusion RCBF has more important role in the development of proteinuria than artery blood pressure. The changes of RCBF may be due to increased renal cortical ET and decreased NO.