胎羊单侧输尿管不完全性梗阻解除前后肾脏组织足细胞表型转化及PAX2、VEGF的表达

目的 从超微结构和分子学方面探讨胎儿期单侧输尿管不完全性梗阻解除后肾脏恢复之机制.方法 26只孕75～85 d的胎羊分3组:梗阻组,对12只胎羊实行宫内手术造成单侧输尿管不完全性梗阻;梗阻解除组,对10只胎羊以同样的手术方法造成单侧输尿管不完全性梗阻,3周后,再次宫内手术解除梗阻;对照组,对4只胎羊实行宫内手术但不结扎输尿管.待胎羊出生后,取其肾脏标本检测病理改变,足细胞表型转化以及PAX2和VEGF的表达变化.结果 梗阻组12只胎羊,其中9只顺利出生;梗阻解除组10只胎羊,其中8只顺利出生;对照组4只胎羊,均顺利生产.与对照组羔羊肾脏相比,梗阻组羔羊梗阻侧肾脏,表现为皮质囊性改变,间质纤维化,肾小球数目显著减少;足细胞足突广泛融合(4.20±1.08)%比(86.79±1.66)%];PAX2表达显著升高(1.43±0.09比2.44±0.09);而VEGF表达明显减少(0.80±0.15比0.33±0.14).解除梗阻后,肾脏的囊性改变大大改善,肾小球数目增加,但细胞外基质沉着仍明显;足细胞足突融合减轻(41.18±3.13)%比(86.79±1.66)%];VEGF的表达显著升高(2.08±0.21比0.33±0.14);PAX2的表达也有一定程度的恢复(2.05±0.14比2.44±0.09).结论 通过对胎羊单侧输尿管不完全性梗阻解除前后肾脏组织病理改变、足细胞表型转化以及PAX2和VEGF表达变化的观察,说明宫内干预能减缓甚至逆转输尿管不完全性梗阻所致的肾脏损伤性改变.

Abstract：

Objective To investigate ultrastructure and molecular change of kidneys after correction of partial unilateral ureteral obstruction. Methods The 26 fetal lambs at 75-85 days of gestation were divided into 3 groups. Obstructed group: partial unilateral ureteral obstruction was achieved with intrauterine surgery in 12 fetal lambs. Decompressed group: partial unilateral ureteral obstruction in 10 fetal lambs first was released 3 weeks later by intrauterine surgery. Control group: a sham operation was performed. The kidneys of the lambs were removed after birth to study the transformation of podocytes as well as expression of paired-box 2 (PAX2) and vascular endothelial growth factor (VEGF). Results Overall, 21 fetal lambs survived: 9 from the obstructed group, 8 from the decompressed group, and 4 from the control group. Compared with the control kidneys, the obstructed kidneys showed cysts of various sizes in the cortex, fibrosis of the interstitial tissue, significantly decreased number of glomeruli, severer podocyte foot process fusion (4. 20 ± 1. 08% vs 86.79 ± 1. 66%) , markedly increased PAX2 (1. 43 ± 0. 09 vs 2. 44 ± 0. 09) and decreased VEGF expressions (0. 80 ± 0. 15 vs 0. 33 ± 0. 14). However, in the decompressed kidneys, the cystic changes decreased, number of glomeruli increased, but extracellular matrix (ECM) deposition was still obvious, fusion of the podocyte foot processes was reduced (41. 18±3. 13% vs 86. 79± 1. 66%), VEGF expression was significantly increased (2. 08 ± 0. 21 vs 0. 33 ± 0. 14) , and expression of PAX2 was restored to some extent (2. 05 ± 0. 14 vs 2. 44 ± 0. 09) in decompressed kidneys. Conclusions Relief of obstruction in utero can reverse the development of nephropathy, evidenced by the phenotype transformation of podocytes, expression of PAX2 and VEGF.

Effects of antenatal intervention on the phenotype transformation of podocytes and expressions of PAX2 and VEGF in kidneys of fetal lambs with partial unilateral ureteral obstruction

Objective To investigate ultrastructure and molecular change of kidneys after correction of partial unilateral ureteral obstruction. Methods The 26 fetal lambs at 75-85 days of gestation were divided into 3 groups. Obstructed group: partial unilateral ureteral obstruction was achieved with intrauterine surgery in 12 fetal lambs. Decompressed group: partial unilateral ureteral obstruction in 10 fetal lambs first was released 3 weeks later by intrauterine surgery. Control group: a sham operation was performed. The kidneys of the lambs were removed after birth to study the transformation of podocytes as well as expression of paired-box 2 (PAX2) and vascular endothelial growth factor (VEGF). Results Overall, 21 fetal lambs survived: 9 from the obstructed group, 8 from the decompressed group, and 4 from the control group. Compared with the control kidneys, the obstructed kidneys showed cysts of various sizes in the cortex, fibrosis of the interstitial tissue, significantly decreased number of glomeruli, severer podocyte foot process fusion (4. 20 ± 1. 08% vs 86.79 ± 1. 66%) , markedly increased PAX2 (1. 43 ± 0. 09 vs 2. 44 ± 0. 09) and decreased VEGF expressions (0. 80 ± 0. 15 vs 0. 33 ± 0. 14). However, in the decompressed kidneys, the cystic changes decreased, number of glomeruli increased, but extracellular matrix (ECM) deposition was still obvious, fusion of the podocyte foot processes was reduced (41. 18±3. 13% vs 86. 79± 1. 66%), VEGF expression was significantly increased (2. 08 ± 0. 21 vs 0. 33 ± 0. 14) , and expression of PAX2 was restored to some extent (2. 05 ± 0. 14 vs 2. 44 ± 0. 09) in decompressed kidneys. Conclusions Relief of obstruction in utero can reverse the development of nephropathy, evidenced by the phenotype transformation of podocytes, expression of PAX2 and VEGF.