人胚胎肾组织形态发生与PAX2表达

Histogenesis of Kidney and PAX Expression of Developing Kidney in Humans

[目的]通过观察人类肾组织形态发生和PAX2在发育肾的表达模式,以了解肾正常形态发生与其功能的联系,认识PAX2在肾发生中所起的重要作用.[方法]通过HE染色观察18例8～34周龄胎儿肾组织标本,研究肾组织形态发生,同时采用免疫组化法分析PAX2在胚胎肾的表达模式.[结果]HE染色显示:①肾发生带位于肾皮质外侧,紧贴肾包膜,随胎龄增加逐渐减少,胎龄33～34周消失;②肾小球沿输尿管芽'T'型分支,两侧成对出现,越近肾髓质中心肾小球越趋向成熟,肾发生带内见不到成熟期肾小球.8～9周龄可见第1～2代成熟期肾小球,19周之前肾小球增加较快,19周时约达8代,34周约为11～12代;原始肾小管伴随肾小球成熟而逐渐成熟,C-期后可看出近端和远端肾小管明显结构差异.免疫组化可见:①输尿管芽末端、压缩间充质细胞PAX2呈强阳性表达,肾囊泡、comma-型小体也表达强烈;②S-型小体原始肾小管部位PAX2表达明显,S-型小体的原始足细胞和C-期原始足细胞PAX2表达有些微弱或不表达,有些表达仍较明显;③成熟肾小球足细胞未检测到PAX2表达,壁层上皮细胞有些持续存在表达,有些无表达;④在发育后期阶段近端小管和远端小管PAX2表达进行性减少,少数仍存在远端小管微弱表达,集合管表达持续存在.[结论]①人胚胎肾单位形成呈明显由内向外的放射状特征,外侧为最不成熟肾小球,第1～2代成熟肾小球出现在8～9周龄,19周时已形成大部分成熟期肾小球,33～34周肾小球分化结束.②输尿管芽分支多寡是决定肾小球和肾小管数量的关键.③PAX2主要参与早期肾小球和肾小管上皮细胞的分化发育,且存在有个体表达特异性,部分胎儿PAX2基因关闭时间较文献报道延迟.

[Objective]To observe histogenesis of human kidney and pattern of PAX2 expression in fetal kidney, in order to fadlitate further analysis of the relationship between PAX2 expression and kidney development. [Methods]The histogensis of human fetal kidney was studied within 8-34 weeks gestation by HE staining. Immunohistochemisty was used to investigate the PAX2 expression in the fetal kidney. [Results]①HE staining displayed that the nephrogenesis zone lacated outside renal cortex and decreased gradually with age, disappearing in 33-34 wks gestation. We also noticed that the double glomeruli developed beside the T-model branching ureteric-bud and that M-stage glomerulus had occurred in the kidney of 8-9 wks gestation with recognizable proximal and distal tubules, glomerular numbers increasing with ages, about 8 generations in 19 wks gestation age and 11 or 12 generations in 33 -34 wks. ②PAX2 expression was mainly in the nephrogenesis zone. The intense immunostaining of PAX2 was showed in ureteric bud tip, condensing mesenchyme, renal vesicle and comma-shaped body. The staining of primitive tubules was evident. Individual difference of PAX2 expression occurred in the primitive podocytes of S-shaped body and immature podocytes of glomeruli of C-stage, as well as in parietal epithelial cells, where some cells showed no expression, yet the others powerful expression. Attenuation of PAX2 was detected in tubules in later stage of renal development, but a few of distal tubules and collecting tubules expressing continuously. [Conclusion]①The glomeruli development presents a radiated feature toward renal cortex and is more immature outside cortex than inside, its differentiation finished about 33 to 34wks gestation age.②The number of branching ureteric bud could control nephron developmental decisions.③ PAX2 is an important factor regulating differentiation of early nephron in humans. The expression of PAX2 presents individual specificity in developing kidney, the time of switch off of PAX2 gene may be in some individuals posterior to that of literature report.