The influence of p53 protein expression on kidney development in rats with intrauterine growth restriction / 中国新生儿科杂志

ABSTRACT

Objective To study the effect of renal p53 protein expression on kidney development in rats with intrauterine growth restriction ( IUGR) . Methods Pregnant rats were randomly assigned into normal group, IUGR group and L-Arg treated group. Normal group were fed with normal diet (21％protein). IUGR group and L-Arg treated group were fed with low-protein diet (10％ protein). During lactation, maternal rats in the three groups were all fed with normal diet. Maternal rats in L-Arg treated group were given additional special drinking water ( L-Arg200 mg/kg) , while maternal rats in normal and IUGR group were given normal drinking water. Offspring weaned after 21 d and had free access to normal rodent diet and water. When the pups grew up to 2 m, the number of glomeruli was counted using acid digestion method, the proliferation and apoptosis of glomerular and tubular cells were studied using TUNEL and Ki-67 immunohistochemistry, and the ultrastructure of epithelial cells was determined by electron microscopy. At 7 d, 21 d, 2 m and 3 m, p53 protein expression in renal tissue was measured by Western blot, respectively. Results At 2 m, the number of glomerulus ( right kidney) in IUGR group was significantly lower than normal group [(23 647±541) vs. (27 689±492), P＜0. 01]; the index of renal cell apoptosis in IUGR group was higher than normal group [(21. 9 ± 2. 0) vs. (16. 7 ± 2. 5), P＜0. 05];however, IUGR group and normal group had no statistically significant difference (P＞0. 05). The proliferation of mesangial cells was found in IUGR and L-Arg treated group, but not in normal group. And the extent of proliferation in L-Arg treated group was lesser than IUGR group. A reduction of foot process and partial fusion of foot process could be observed in IUGR group and L-Arg treated group while the foot process morphology in normal group was normal. At 2 m and 3 m, p53 protein level in IUGR group and L-Arg treated group were higher than normal group [ 2 m ( 0. 28 ± 0. 03 ) and ( 0. 21 ± 0. 01 ) vs. (0. 10±0. 02);3 m(0. 39±0. 04) and (0. 26±0. 02) vs. (0. 17±0. 03);P＜0. 01], while IUGR group higher than L-Arg treated group ( P＜0. 05 ) . Conclusions The kidney of IUGR rats showed reduced glomerular number, increased renal cell apoptosis, enhanced p53 protein expression, increased proliferation of glomerular mesangial cells, decreased foot process, and partial fusion of foot process. And L-Arg could to some extent improve the organizational structure of the kidney in IUGR rats.