Haylor J L, McKillop I H, Oldroyd S D, El Nahas M A
Sheffield Kidney Institute, Northern General Hospital, Sheffield, UK.
Nephrol Dial Transplant. 2000 Jan;15(1):87-92. doi: 10.1093/ndt/15.1.87.
A role for insulin-like growth factor-I (IGF-I) as a mediator of renal hyperfiltration and hyperperfusion following unilateral nephrectomy (UNx) has been examined.
Adult male Wistar rats were subjected to either left UNx or sham operation. Twenty one days after surgery, the right kidney was removed under barbiturate anaesthesia, and renal function was measured ex vivo using an isolated rat kidney perfusion system. The glomerular filtration rate was assessed from the renal clearance of [(14)C]inulin.
UNx stimulated renal growth as shown by a significantly higher (P<0.02) tissue dry weight in kidneys from UNx (0.45+/-0.02 g) than from sham-operated rats (0.31+/-0.02 g). Compensatory hyperfiltration could be detected ex vivo; kidneys obtained from UNx rats having a significantly higher (P<0.05) [(14)C]inulin clearance (0.75+/-0.08 ml/min, n=8) than kidneys obtained from sham-operated animals (0.39+/-0.05 ml/min, n=8). Compensatory hyperperfusion was also detected ex vivo; kidneys obtained from UNx rats having a significantly higher (P<0.05) renal perfusate flow (28.2+/-2.7 ml/min) than kidneys obtained from sham-operated rats (22.5+/-0.8 ml/min). Following perfusion with either 50 microg monoclonal IGF-I antibody (n=4) or 6.5 microM genistein (n=4), an inhibitor of tyrosine kinase, no significant difference in [(14)C]inulin was observed between kidneys obtained from either UNx or sham-operated rats. In contrast to hyperfiltration, renal hyperperfusion remained unaffected by the IGF-I antibody and was only reduced by 30% following genistein administration.
The results suggest a role for renal IGF-I as a mediator of compensatory hyperfiltration in the rat.
胰岛素样生长因子-I（IGF-I）作为单侧肾切除（UNx）后肾脏高滤过和高灌注的介质作用已得到研究。
成年雄性Wistar大鼠接受左肾切除或假手术。术后21天，在巴比妥类麻醉下切除右肾，并使用离体大鼠肾脏灌注系统体外测量肾功能。通过[¹⁴C]菊粉的肾清除率评估肾小球滤过率。
UNx刺激了肾脏生长，UNx大鼠肾脏的组织干重（0.45±0.02 g）显著高于假手术大鼠（0.31±0.02 g）（P<0.02）。体外可检测到代偿性高滤过；UNx大鼠的肾脏[¹⁴C]菊粉清除率（0.75±0.08 ml/min，n = 8）显著高于假手术动物的肾脏（0.39±0.05 ml/min，n = 8）（P<0.05）。体外也检测到代偿性高灌注；UNx大鼠的肾脏肾灌注液流量（28.2±2.7 ml/min）显著高于假手术大鼠的肾脏（22.5±0.8 ml/min）（P<0.05）。在用50μg单克隆IGF-I抗体（n = 4）或6.5μM酪氨酸激酶抑制剂染料木黄酮（n = 4）灌注后，UNx大鼠和假手术大鼠的肾脏之间[¹⁴C]菊粉清除率没有显著差异。与高滤过相反，肾脏高灌注不受IGF-I抗体影响，仅在给予染料木黄酮后降低30%。
结果表明肾脏IGF-I在大鼠代偿性高滤过中起介质作用。
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