Insulin-like growth factor-I increases p21 expression and attenuates cisplatin-induced acute renal injury in rats
Insulin-like growth factor-I increases p21 expression and attenuates cisplatin-induced acute renal injury in rats
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DOI：
10.1007/s10157-003-0263-x
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发表时间：
2004-03
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影响因子：
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通讯作者：
H. Yasuda;Akihiko Kato;T. Miyaji;Hua Zhou;A. Togawa;A. Hishida
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文献类型：
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作者：
H. Yasuda;Akihiko Kato;T. Miyaji;Hua Zhou;A. Togawa;A. Hishida
外源性胰岛素样生长因子-I(IGF-I)可促进缺血性肾损伤的恢复，但其对顺铂(CDDP)肾毒性的影响及其减轻肾损伤的机制尚不清楚。顺铂前后24 h每日1次，每次5 mg/kg，静脉滴注。结果治疗后第5天，重组人胰岛素样生长因子-I治疗组大鼠血肌酐(0.92±0.11vs1.50±0.15 mg/dl；P≪0.05)、肾小管损伤评分、外延髓外条带细胞凋亡率/管上皮细胞数均显著降低(P≪0.05)。P21阳性核数(5.15±0.19vs3.45±0.42/×400hpf；P≪0.05)和增殖细胞核抗原阳性核数(28.61±1.89vs18.26±2.14/×400hpf；P≪0.05)明显增加，而cyClinD1阳性细胞数(3.3±0.3vs6.3±1.7/×400hpf)明显减少；结论重组人IGF-I可增加肾组织中p21和≪的表达，但降低细胞周期蛋白D1的表达。外源性重组人胰岛素样生长因子-I可能通过使细胞周期停滞于G1/S期而减轻肾损伤。
BackgroundExogenous insulin-like growth factor-I (IGF-I) promotes recovery from ischemic renal injury, but its effect on cisplatin (CDDP)-induced nephrotoxicity and its mechanisms for the attenuation of renal injury are unknown.MethodsWe administered recombinant human IGF-I (rhIGF-I, 150 µg/day, i.p.) once a day 24 h prior to and after CDDP (5 mg/kg, i.v.) injection in rats.ResultsThe rhIGF-I treatment significantly decreased serum creatinine (0.92 ± 0.11 vs 1.50 ± 0.15 mg/dl;P≪ 0.05), the tubular damage score, and the ratio of apoptotic cells to tubular epithelial cells in the outer stripe of the outer medulla on day 5 (P≪ 0.05). rhIGF-I significantly increased the numbers of p21-positive nuclei (5.15 ± 0.19 vs 3.45 ± 0.42/×400 high-power field (HPF);P≪ 0.05) and proliferating cell nuclear antigen (PCNA)-positive nuclei (28.61 ± 1.89 vs 18.26 ± 2.14/×400 HPF;P≪ 0.05), but decreased the number of cyclin D1-positive cells (3.3 ± 0.3 vs 6.3 ± 1.7/×400 HPF;P≪ 0.05) on day 3. rhIGF-I did not alter 5-bromo-3-deoxyuridine (BrdU) incorporation.ConclusionsOur findings suggested that rhIGF-I increased renal p21 and PCNA expression, but reduced cyclin D1 expression in CDDP-treated kidneys. Exogenous rhIGF-I may ameliorate renal damage, in part by stopping the cell cycle at G1/S phase.