Vehaskari V M, Aviles D H, Manning J
Department of Pediatrics, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112, USA.
Kidney Int. 2001 Jan;59(1):238-45. doi: 10.1046/j.1523-1755.2001.00484.x.
Epidemiological studies have suggested that low birthweight is a risk factor for the development of essential hypertension in adulthood, but the mechanism is unknown.
A rat model of intrauterine growth retardation was employed. Pregnant Sprague-Dawley rats were kept on 6% protein or on control isocaloric 20% protein diet from gestational day 12 until term. Systolic blood pressures of the offspring were monitored by the tail cuff method. Apoptosis was determined by the TUNEL method, cell proliferation by anti-Ki67 antibody, and the total number of glomeruli by the maceration method. Results are mean +/- SD.
The kidney and body sizes of the offspring from the low-protein pregnancies (LP) were proportionately decreased at birth. Full catch-up growth occurred during the first two weeks of life. The kidneys were normal by standard histology but exhibited increased apoptosis without increased cell proliferation at eight weeks of age. The total number of glomeruli per kidney was decreased by 28% in males (P < 0.001) and by 29% in females (P < 0.01). By eight weeks of age, both male and female LP had systolic blood pressures that were 20 to 25 mm Hg higher than those of control animals (P < 0.001), and their 18-month survival was significantly decreased (44 vs. 93%, P < 0.01). During the prehypertensive stage, at four weeks of age, PRA in LP was low (1.7 +/- 1.4 vs. 19.7 +/- 5.5 ng/mL/hour in males, P < 0.0001; 4.9 +/- 2.2 vs. 14.9 +/- 7.2 ng/mL/hour in females, P < 0.0005), and aldosterone was high (93 +/- 15 vs. 54 +/- 27 pg/mL in males, P < 0. 005; 93 +/- 20 vs. 48 +/- 20 pg/mL in females, P < 0.0001). Smaller but significant differences persisted at eight weeks of age.
Adult blood pressure profile is susceptible to prenatal programming by maternal low-protein diet in the rat. The mechanism may involve an altered renin-aldosterone axis and a deficit in total nephron number.
流行病学研究表明，低出生体重是成年后患原发性高血压的一个危险因素，但其机制尚不清楚。
采用子宫内生长迟缓大鼠模型。从妊娠第12天至足月，将怀孕的斯普拉格-道利大鼠分别给予6%蛋白质饮食或等热量的20%蛋白质对照饮食。通过尾套法监测子代的收缩压。采用TUNEL法测定细胞凋亡，用抗Ki67抗体测定细胞增殖，用浸软法测定肾小球总数。结果以平均值±标准差表示。
低蛋白妊娠（LP）子代的肾脏和身体大小在出生时成比例减小。在出生后的前两周实现了完全追赶生长。通过标准组织学检查，肾脏外观正常，但在8周龄时显示细胞凋亡增加，而细胞增殖未增加。雄性大鼠每只肾脏的肾小球总数减少28%（P<0.001），雌性大鼠减少29%（P<0.01）。到8周龄时，雄性和雌性LP大鼠的收缩压均比对照动物高20至25 mmHg（P<0.001），其18个月生存率显著降低（44%对93%，P<0.01）。在高血压前期，即4周龄时，LP大鼠的肾素活性较低（雄性为1.7±1.4对19.7±5.5 ng/mL/小时，P<0.0001；雌性为4.9±2.2对14.9±7.2 ng/mL/小时，P<0.0005），而醛固酮水平较高（雄性为93±15对54±27 pg/mL，P<0.005；雌性为93±20对48±20 pg/mL，P<0.0001）。在8周龄时仍存在较小但显著的差异。
在大鼠中，成年血压状况易受母体低蛋白饮食的产前编程影响。其机制可能涉及肾素-醛固酮轴的改变和总肾单位数量的减少。
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