胰岛素样生长因子-Ⅰ在缺血性急性肾功衰竭中的作用

The Role of Insulin-like Growth Factor-Ⅰ in Ischemic Acute Renal Failure

目的 探讨胰岛素样生长因子 - (IGF- )在缺血性急性肾功能衰竭 (IARF)中的作用机制。方法 将 32只大鼠夹闭双肾动脉 45分钟建立 IARF模型 ,并随机分为 :IARF组 ,IGF- 组 (16只 ,每日皮下注射rh IGF- 2 5 0 ng/kg1次。另 16只大鼠为假手术对照组。观察大鼠内生肌酐清除率 (Ccr) ,2 4小时尿蛋白 ,β2 -微球蛋白 (β2 - MG) ,血、尿 IGF- ,表皮生长因子 (EGF) ,血栓素 B2 (TXB2 ) ,6 -酮 -前列腺素 F1α(6 - keto- PGF1α)水平及肾脏组织形态学改变。结果 缺血后 IARF组 Ccr显著下降 ,2 4小时尿蛋白 ,β2 - MG,血、尿 TXB2 及肾重 /体重增高 ,血、尿 EGF,6 - keto- PGF1α及尿 IGF- 1水平降低 ,与对照组相比差异显著。IGF- 组 Ccr升高 ,且较快恢复到对照水平 ;2 4小时尿蛋白 ,β2 - MG及血尿 TXB2 下降 ,血、尿 EGF,6 - keto- PGF1α及尿 IGF- 水平增高 ;肾组织学观察肾小管损伤程度减轻 ,肾小管上皮再生恢复快。结论 IGF- 可改善 IAFR肾功能 ,减轻肾小管损伤程度 ,具有促进肾小管上皮再生恢复的作用。

Objective To explore the role of insulin-like growth factor-Ⅰ(IGF-Ⅰ) in ischemic acute renal failure(IARF). Methods Wistar rats were divided into three groups: sham-operation group (n=16); IARF group (n=16), in which the rats were subjected to 45 minutes of bilateral renal ischemia; IGF-1 group (n=16), in which a subcutaneous injection of rhIGF-Ⅰ(250ng/kg) was given to the rats per day after the release of clamped bilateral renal arteries. Creatinine clearance(Ccr), urine protein per 24 hours, serum and urine β 2-microglobulin (β 2-MG),IGF-1, epidermal growth factor(EGF), thromboxane(TXB 2), prostaglandin F1alpha(PGF 1α) were measured and renal histology was observed. Results Ccr concentration in IARF group decreased obviously, while proteinuria per 24 hours, β 2-MG, kidney weight/body weight, serum and urine levels of TXB 2 were higher and the serum and urine levels of EGF, PGF 1α and urine IGF were lower than those in the control group. In the IFG-Ⅰ group, the Ccr concentration increased and showed a more rapid return toward base-line; the serum and urine levels of TXB 2, urine protein per 24 hours and β 2-Mg reduced, and the serum and urine levels of EGF, PGF 1α and urine IGF increased as compared with those in the IARF group. The kidneys from rats that had received IGF-Ⅰ were improved in histopathologically. Conclusion IGF-Ⅰ improves renal function, hastens recovery and accelearates regeneration of damaged tubular epithelia following ischemic acute renal failure.