糖尿病早期大鼠肾小管上皮细胞凋亡与增殖的观察

An Observation on Apoptosis and Proliferation of the Renal Tubular Epithelium of rats in the Early Phase of Diabetes Mellitus

为了解糖尿病早期肾小管上皮细胞（ｒｅｎａｌｔｕｂｕｌａｒｅｐｉｔｈｌｉａｌｃｅｌｌｓ， 简称ＲＴＥＣｓ） 是否有损害，探讨微蛋白尿发生的机制。方法：四氧嘧啶（ａｌｌｏｘａｎ）尾静脉注射（５０ ｍｇ／ｋｇ）雄性Ｗｉｓｔａｒ 大鼠６０ 只，石蜡包埋肾切片经ＴＵＮＥＬ法和ＰＣＮＡ、ＢｒｄＵ免疫组化染色。结果：成模后２０～６０ ｄ 和９０～１４０ ｄ，ＴＵＮＥＬ法阳性ＲＴＥＣｓ 主要出现在远端小管、髓质肾小管、集合管。ＰＣＮＡ、ＢｒｄＵ 免疫组化染色阳性ＲＴＥＣｓ 主要见于注射后４０ ｄ、１３０ ～１４０ ｄ 皮质和髓质肾小管、集合管，其出现的部位、数量与凋亡基本一致。结论：本研究结果表明，高糖对ＲＴＥＣｓ 是一种亚坏死性损伤剂，导致其凋亡发生率增加，同时可能影响肾小管重吸收和分泌功能。ＲＴＥＣｓ 增殖发生略晚，但与凋亡发生率相匹配。笔者推测借此种机制糖尿病早期ＲＴＥＣｓ 的数目和肾小管的形态得以保护，造成一般组织学方法不能将ＲＴＥＣｓ 的损伤检测出来。

In order to know whether or not the renal tubular epithelial cells(RTECs)are damaged during the early phase of diabetes mellitus(DN),and to understand the pathogenic mechanism of micro protein urine, we designed this experiment. MATERIAL AND METHODS:60 male Wistar rats were injected alloxan (50mg/kg)through the tail vein; the paraffin embedded sections of kidneys were displayed by TUNEL method, PCNA and BrdU immunohistochemical staining. RESULTS:①During 20～60 days and 90～140 days after the injection, TUNEL(+) RTECs were mainly distributed in the distant tubules, the medullar tubules, and the collection tubules. The TUNEL(+) cells possessed typical morphological characteristics of apoptosis, and apoptotic bodies were occasionally found. With the extension of DN, the majority of TUNEL(+) RTECs were located in the medulla. ②On the 40 th day and during 130～140 days after the injection, the PCNA and BrdU positive immunostained RTECs were mainly distributed in the cortical and medullar tubules and collecting tubules. Their location and number were the same as those of the apoptotic RTECs. CONCLUSION:The above results suggested high blood sugar was a subnecrotic damage agent to RTECs, and could increase the apoptotic cells, and might offect the reabsorption and secretion of the renal tubules. The proliferation of RTECs occurred slightly later, and its rate matched up to apoptosis of RTECs. We guessed that in the early phase of DN the normal quantity of RTECs and morphological characteristics of the renal tubules were maintained through this new balance, which caused the damage of RTECs not to be observed by ordinary histological methods.