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胰岛素样生长因子-1对新生兔低氧血症性肾功能不全的有益作用。

Beneficial effect of insulin-like growth factor-1 on hypoxemic renal dysfunction in the newborn rabbit.

作者信息

Prévot Anne, Julita Monique, Tung David K, Mosig Dolores

机构信息

Nephrology Unit, Department of Pediatrics, Lausanne University Medical Center (CHUV), Lausanne, Switzerland.

出版信息

Pediatr Nephrol. 2009 May;24(5):973-81. doi: 10.1007/s00467-008-1098-1. Epub 2009 Jan 24.

Abstract

Acute normocapnic hypoxemia can cause functional renal insufficiency by increasing renal vascular resistance (RVR), leading to renal hypoperfusion and decreased glomerular filtration rate (GFR). Insulin-like growth factor 1 (IGF-1) activity is low in fetuses and newborns and further decreases during hypoxia. IGF-1 administration to humans and adult animals induces pre- and postglomerular vasodilation, thereby increasing GFR and renal blood flow (RBF). A potential protective effect of IGF-1 on renal function was evaluated in newborn rabbits with hypoxemia-induced renal insufficiency. Renal function and hemodynamic parameters were assessed in 17 anesthetized and mechanically ventilated newborn rabbits. After hypoxemia stabilization, saline solution (time control) or IGF-1 (1 mg/kg) was given as an intravenous (i.v.) bolus, and renal function was determined for six 30-min periods. Normocapnic hypoxemia significantly increased RVR (+16%), leading to decreased GFR (-14%), RBF (-19%) and diuresis (-12%), with an increased filtration fraction (FF). Saline solution resulted in a worsening of parameters affected by hypoxemia. Contrarily, although mean blood pressure decreased slightly but significantly, IGF-1 prevented a further increase in RVR, with subsequent improvement of GFR, RBF and diuresis. FF indicated relative postglomerular vasodilation. Although hypoxemia-induced acute renal failure was not completely prevented, IGF-1 elicited efferent vasodilation, thereby precluding a further decline in renal function.

摘要

急性等碳酸血症性低氧血症可通过增加肾血管阻力(RVR)导致功能性肾功能不全,进而引起肾灌注不足和肾小球滤过率(GFR)降低。胰岛素样生长因子1(IGF-1)在胎儿和新生儿中的活性较低,在缺氧时会进一步降低。对人类和成年动物给予IGF-1可诱导肾小球前和肾小球后血管舒张,从而增加GFR和肾血流量(RBF)。在低氧血症诱导的肾功能不全的新生兔中评估了IGF-1对肾功能的潜在保护作用。对17只麻醉并机械通气的新生兔评估了肾功能和血流动力学参数。低氧血症稳定后,静脉推注生理盐水(时间对照)或IGF-1(1mg/kg),并在六个30分钟时间段内测定肾功能。等碳酸血症性低氧血症显著增加了RVR(+16%),导致GFR(-14%)、RBF(-19%)和尿量(-12%)降低,滤过分数(FF)增加。生理盐水导致受低氧血症影响的参数恶化。相反,尽管平均血压略有但显著下降,但IGF-1阻止了RVR的进一步增加,随后GFR、RBF和尿量得到改善。FF表明肾小球后血管相对舒张。尽管低氧血症诱导的急性肾衰竭未被完全预防,但IGF-1引起了出球小动脉舒张,从而防止了肾功能的进一步下降。

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