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成年大鼠产前接受地塞米松后的肾功能

Renal function in adult rats subjected to prenatal dexamethasone.

作者信息

Martins João P C, Monteiro Josélia C, Paixão Ana D O

机构信息

Department of Physiology and Pharmacology, Biological Science Center, Federal University of Pernambuco, Recife, PE, Brazil.

出版信息

Clin Exp Pharmacol Physiol. 2003 Jan-Feb;30(1-2):32-7. doi: 10.1046/j.1440-1681.2003.03787.x.

Abstract
  1. Prenatal dexamethasone leads to low birth weight and compromises organogenesis, but its effects on nephrogenesis in male and female rats have not yet been investigated extensively. Reduced renal mass may be responsible for hypertension and renal haemodynamic and morphological adjustments to maintain the glomerular filtration rate (GFR). Subsequently, these compensatory mechanisms determine glomerular sclerosis and irreversible reduction in GFR. When a high-protein diet is associated with reduced renal mass, it accelerates glomerular sclerosis and the decline in renal function. The aim of the present study was to evaluate whether rats subjected to prenatal dexamethasone and a high-protein diet during growth present a premature decline in renal function. 2. The number of nephrons and renal haemodynamics were estimated in Wistar rats fed a high-protein diet (40% protein) after weaning in offspring of dams treated with either dexamethasone (0.1 mg/kg per day) or its vehicle (control; physiological solution, 0.1 mL/kg per day) during gestation. 3. At 70 days of age, rat offspring were anaesthetized and prepared surgically for renal haemodynamic measurements. 4. Mean arterial pressure (MAP), renal blood flow (RBF) and GFR were measured using a blood pressure transducer, a flow probe and inulin clearance, respectively. 5. The number of nephrons was counted using the acid-maceration technique. 6. Dexamethasone during pregnancy induced a lower weight gain in the dams (65%; P < 0.0001) and a lower birth weight in both male and female offspring (14 and 13%, respectively; P < 0.01). 7. Compared with control, the number of nephrons in male rats was reduced by 13% (30 703 +/- 1262 vs 26 308 +/- 1305, respectively; P < 0.05), but was unaltered in female rats (23 197 +/- 553 vs 24 231 +/- 1009, respectively). 8. Male and female rats did not show any alteration in MAP. In addition, they did not show any alteration in renal vascular resistance, RBF, filtration fraction or GFR. 9. In conclusion, prenatally administered dexamethasone (0.1 mg/kg during the entire pregnancy) induced a low birth weight. The magnitude of the reduction in nephrogenesis in male offspring from mothers treated with dexamethasone was not sufficient to alter renal function (measured at 70 days), even when rats had been fed a high-protein diet.
摘要
  1. 产前使用地塞米松会导致低出生体重并影响器官发生,但其对雄性和雌性大鼠肾发生的影响尚未得到广泛研究。肾质量降低可能是高血压以及肾脏血流动力学和形态学调整以维持肾小球滤过率(GFR)的原因。随后,这些代偿机制会导致肾小球硬化和GFR的不可逆降低。当高蛋白饮食与肾质量降低相关联时,会加速肾小球硬化和肾功能下降。本研究的目的是评估在生长过程中接受产前地塞米松和高蛋白饮食的大鼠是否会出现肾功能过早下降。2. 在妊娠期间用要么地塞米松(0.1毫克/千克/天)要么其赋形剂(对照;生理溶液,0.1毫升/千克/天)处理的母鼠的后代断奶后,对喂食高蛋白饮食(40%蛋白质)的Wistar大鼠的肾单位数量和肾脏血流动力学进行评估。3. 在70日龄时,将大鼠后代麻醉并进行手术准备以测量肾脏血流动力学。4. 分别使用血压换能器、流量探头和菊粉清除率来测量平均动脉压(MAP)、肾血流量(RBF)和GFR。5. 使用酸浸技术计算肾单位数量。6. 孕期使用地塞米松导致母鼠体重增加降低(65%;P<0.0001),并且雄性和雌性后代的出生体重均降低(分别为14%和13%;P<0.01)。7. 与对照组相比,雄性大鼠的肾单位数量减少了13%(分别为30703±1262和26308±1305;P<0.05),但雌性大鼠的肾单位数量未改变(分别为23197±553和24231±1009)。8. 雄性和雌性大鼠的MAP均未显示任何改变。此外,它们的肾血管阻力、RBF、滤过分数或GFR均未显示任何改变。9. 总之,产前给予地塞米松(整个孕期0.1毫克/千克)会导致低出生体重。即使大鼠喂食高蛋白饮食,用其处理的母亲所生雄性后代肾发生减少程度也不足以改变肾功能(在70日龄时测量)。

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