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目的探讨p53蛋白表达对宫内生长受限(IUGR)大鼠肾脏发育的影响。方法孕鼠随机分为正常组、IUGR组和干预组。正常组孕鼠以普通饲料(含21%蛋白)喂养;IUGR组和干预组大鼠孕期均采用低蛋白饲料(含10%蛋白)喂养。仔鼠出生后,IUGR组母鼠普通饲料喂养;干预组母鼠在普通饲料喂养的基础上,每日于饮水中添加左旋精氨酸(L-Arg)200 mg/kg。仔鼠2月龄取肾脏组织,酸消化法进行肾小球数目计数,观察肾小球和肾小管细胞增生和凋亡情况,以及上皮细胞超微结构;采用Western Blot法,观察7天、21天、2月和3月龄仔鼠肾脏p53蛋白的表达。结果 2月龄时,IUGR组大鼠的肾小球数目低于正常组[(23 647±541)比(27 689±492)个/单侧,P<0.01];IUGR组大鼠肾脏细胞凋亡指数高于正常组[(21.9±2.0)比(16.7±2.5)%,P<0.05],两组增生指数差异无统计学意义(P>0.05);IUGR组和干预组肾小球系膜细胞均有增生,滤过膜足突减少及部分融合,但干预组系膜细胞增生少于IUGR组,正常组系膜细胞无明显增生,滤过膜足突形态正常。各组大鼠肾脏在7天和21天均未见p53蛋白的明显表达,2月龄和3月龄时IUGR组和干预组p53蛋白表达均高于正常组[2月:(0.28±0.03)、(0.21±0.01)比(0.10±0.02);3月:(0.39±0.04)、(0.26±0.02)比(0.17±0.03);P均<0.01],IUGR组高于干预组(P<0.05)。结论 IUGR大鼠肾小球数目减少,并存在肾脏细胞凋亡增加和p53蛋白表达增强,出现肾小球系膜细胞增生、滤过膜足突减少及部分融合。使用L-Arg后可以在一定程度上改善IUGR大鼠肾脏组织结构。
Objective To investigate the effect of p53 protein expression on the development of kidney in IUGR rats. Methods Pregnant mice were randomly divided into normal group, IUGR group and intervention group. The normal pregnant rats were fed with normal diet (containing 21% protein). The rats in IUGR group and intervention group were fed with low protein diet (containing 10% protein) during pregnancy. After the offspring was born, the females in IUGR group were fed with the normal diet. The females in the intervention group were given L-arginine (L-Arg) 200 mg / kg daily in the drinking water on the basis of normal feed. At 2 months of age, the kidneys were taken from the kidneys and the number of glomeruli was counted by acid digestion. The proliferation and apoptosis of glomerulus and tubular cells were observed, and the ultrastructure of epithelial cells were observed. The expression of p53 protein in kidneys of day, February and 3 months old pups. Results At 2 months of age, the number of glomeruli in IUGR rats was lower than that in normal rats [(23 647 ± 541) vs (27 689 ± 492) / unilateral, P <0.01] The index of death was higher in the IUGR group and the intervention group than in the normal group [(21.9 ± 2.0) vs (16.7 ± 2.5)%, P <0.05], but there was no significant difference between the two groups (P> 0.05) Cells were hyperplasia, filtration membrane foot process to reduce and partial fusion, but the intervention group mesangial cell proliferation less than IUGR group, no significant proliferation of normal mesangial cells, filtration membrane podocyte morphology was normal. The expression of p53 protein was not observed in the kidneys of 7 and 21 days in each group, and the expression of p53 protein in IUGR group and intervention group was significantly higher than that in the normal group at 2 and 3 months [February: (0.28 ± 0.03) (0.21 ± 0.01) vs (0. 10 ± 0. 02); March: (0.39 ± 0.04), (0.26 ± 0.02) vs (0.17 ± 0.03), P <0.01; ). Conclusions The number of glomeruli in IUGR rats is decreased. There is an increase in renal cell apoptosis and p53 protein expression in IUGR rats. Glomerular mesangial cell proliferation, filtration membrane foot process, and partial fusion occur. The use of L-Arg can improve the renal tissue structure of IUGR rats to a certain extent.