Effects of early postnatal hyperglycaemia on renal cortex maturity, endothelial nitric oxide synthase expression and nephron deficit in mice
Effects of early postnatal hyperglycaemia on renal cortex maturity, endothelial nitric oxide synthase expression and nephron deficit in mice
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DOI：
10.1111/j.1365-2613.2008.00593.x
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发表时间：
2008-08-01
影响因子：
3
通讯作者：
Mandarim-de-Lacerda, Carlos Alberto
中科院分区：
文献类型：
--
作者：
Cunha, Ana Rosa;Aguila, Marcia Barbosa;Mandarim-de-Lacerda, Carlos Alberto
高血糖对链脲佐菌素(STZ)(40 mg/kg)诱导的小鼠肾脏发育的影响在出生后7天和21天进行了研究。取肾脏进行光镜、免疫组织化学和体视学检查。7日龄幼鼠的未成熟肾小球和成熟肾小球分别被评估。用免疫组织化学方法检测增殖细胞核抗原(PCNA)和内皮型一氧化氮合酶(ENOS)的表达。7日龄时，STZ组未成熟/成熟肾小球比率(IMGR)显著高于对照组。STZ组肾小球数量与对照组无差异，但对照组至21日龄肾小球数量增加了20%以上，而STZ组无明显变化。STZ仔鼠肾小管上皮细胞内可见大量的增殖细胞核，而对照组未见。21日龄时，对照组仔鼠肾小球内皮细胞核外层eNOS表达较强，而STZ仔鼠表达较弱。新生早期应用链脲佐菌素干扰了啮齿动物这个阶段的正常肾发生，并导致肾皮质成熟延迟，表现为增殖细胞核抗原和IMGR的表达增加，eNOS的表达减少。
The influence of hyperglycaemia on nephrogenesis on Swiss mice pups treated with streptozotocin (STZ) (40 mg/kg, i.p.) was studied after birth, at 7 and 21 days. Kidneys were prepared for light microscopy, immunohistochemistry and stereology. In 7-day-old pups, both immature and mature glomeruli were evaluated separately. Proliferating cell nuclear antigen (PCNA) and endothelial nitric oxide synthase (eNOS) immunostaining were performed and quantified. At age 7 days, the immature-to-mature glomeruli ratio (IMGR) was significantly higher in the STZ group than in the control group. There was no difference in the number of glomeruli between the STZ and control groups; however, the number of glomeruli increased by more than 20% in the control group until 21 days of age, but not in the STZ group. STZ pups showed numerous PCNA-positive nuclei mainly in tubular cells, but not control pups. At 21 days, eNOS expression in the outer layer of glomerular endothelial nuclei was strong in control pups, but weaker in STZ pups. Treatment with STZ during the early neonatal period disturbs the normal nephrogenesis occurring at this stage of the rodent's life and causes retardation in renal cortical maturity, as indicated by the increase in both PCNA expression and IMGR, and reduction in eNOS expression.