Changes in cellular composition of kidney collecting duct cells in rats with lithium-induced NDI
Changes in cellular composition of kidney collecting duct cells in rats with lithium-induced NDI
复制标题
DOI：
10.1152/ajpcell.00266.2003
复制
发表时间：
2004-04-01
影响因子：
5.5
通讯作者：
Nielsen, S
中科院分区：
文献类型：
--
作者：
Christensen, BM;Marples, D;Nielsen, S
锂处理4周后引起严重多尿，水通道蛋白-2 （AQP-2）表达显著下调，AQP-2免疫反应性明显降低，集管内出现大量未标记AQP-2的细胞。令人惊讶的是，这并不完全是由于aqp -2阴性主细胞的增加，因为双重免疫标记显示大多数aqp -2阴性细胞显示[H+] atp酶标记，这表明它们是插层细胞。此外，多个[H+] atp酶标记的细胞相邻，这在对照大鼠中从未见过。定量证实，与对照组相比，AQP-2标记可检测的收集管细胞比例显著减少：皮质收集管为40 +/- 3.4，对照组为62 +/- 1.8% (P < 0.05, n = 4)；髓内收集管为58 +/- 1.6，对照组为81 +/- 1.3% （P < 0.05, n = 4）。同时，插入（[H+] atp酶阳性）细胞的比例显著增加。尿量、全肾AQP- 2表达、细胞组织、皮层和髓质内主细胞和插层细胞的比例在含锂饮食4周后恢复到控制水平。综上所述，锂处理不仅降低了AQP-2的表达，而且显著且可逆地降低了主细胞的比例，改变了收集管的细胞组织。这些影响可能在锂诱导的肾源性尿崩症中很重要。
Lithium treatment for 4 wk caused severe polyuria, dramatic downregulation in aquaporin-2 (AQP-2) expression, and marked decrease in AQP-2 immunoreactivity with the appearance of a large number of cells without AQP-2 labeling in the collecting ducts after lithium treatment. Surprisingly, this was not all due to an increase in AQP-2-negative principal cells, because double immunolabeling revealed that the majority of the AQP-2-negative cells displayed [H+]ATPase labeling, which identified them as intercalated cells. Moreover, multiple [H+]ATPase-labeled cells were adjacent, which was never seen in control rats. Quantitation confirmed a significant decrease in the fraction of collecting duct cells that exhibited detectable AQP-2 labeling compared with control rats: in cortical collecting ducts, 40 +/- 3.4 vs. 62 +/- 1.8% of controls (P < 0.05; n = 4) and in inner medullary collecting ducts, 58 +/- 1.6 vs. 81 +/- 1.3% of controls (P < 0.05; n = 4). In parallel, a significant increase in the fraction of intercalated ([H+]ATPase-positive) cells was shown. Urine output, whole kidney AQP- 2 expression, cellular organization, and the fractions of principal and intercalated cells in cortex and inner medulla returned to control levels after 4 wk on a lithium-free diet following 4 wk on a lithium-containing diet. In conclusion, lithium treatment not only decreased AQP-2 expression, but dramatically and reversibly reduced the fraction of principal cells and altered the cellular organization in collecting ducts. These effects are likely to be important in lithium-induced nephrogenic diabetes insipidus.