Tanner G A, Gretz N, Shao Y, Evan A P, Steinhausen M
Department of Physiology and Biophysics, Indiana University School of Medicine, Indianapolis 46202, USA.
J Am Soc Nephrol. 1997 Aug;8(8):1222-31. doi: 10.1681/ASN.V881222.
This study examined whether organic anion secretion contributes to fluid accumulation in cysts in polycystic kidney disease. Clearance and micropuncture studies were done on young (7 to 16 wk old), mostly male, heterozygous Han:SPRD cystic rats and healthy control littermate rats. Heterozygous Han:SPRD rats manifest a slowly progressive autosomal dominant polycystic kidney disease that closely resembles the human disorder. Left kidney GFR (polyfructosan clearance), in microl/min per 100 g body wt, averaged 331 +/- 36 (SD) in seven healthy rats and 278 +/- 75 in seven cystic rats. The maximal rate of p-aminohippurate (PAH) secretion, in micromol/min per 100 g body wt, averaged 0.94 +/- 0.24 in healthy rats and 0.83 +/- 0.11 in cystic rats. In these young rats, there were no significant differences in GFR or the maximal rate of PAH secretion despite the presence of cystic disease. Using fluorescence microscopy, it was found that 27 of 29 proximal cysts secreted sulfonefluorescein, an organic anion transported by the PAH system. Transmission electron micrographs of superficial cysts that had secreted sulfonefluorescein demonstrated the presence of both normal-appearing and poorly differentiated proximal tubule cells. Segments of superficial proximal convoluted tubules or cysts, isolated by upstream and downstream wax blocks, failed to accumulate fluid when PAH was infused intravenously. With the stationary microperfusion technique, PAH secretion by both normal and cystic nephrons was demonstrated. It is concluded that most proximal cystic epithelia retain the ability to secrete organic anions. Secretion of organic anions, however, does not appear to contribute in any substantial way to fluid accumulation in cysts in the rat kidney.
本研究检测了有机阴离子分泌是否促使多囊肾病囊肿内液体蓄积。对年轻(7至16周龄)、大多为雄性的杂合子Han:SPRD囊性大鼠及健康对照同窝出生大鼠进行了清除率和微穿刺研究。杂合子Han:SPRD大鼠表现出一种缓慢进展的常染色体显性多囊肾病,与人类疾病极为相似。以每100克体重微升/分钟计算,7只健康大鼠的左肾肾小球滤过率(多聚果糖清除率)平均为331±36(标准差),7只囊性大鼠为278±75。以每100克体重微摩尔/分钟计算,健康大鼠对氨基马尿酸(PAH)的最大分泌率平均为0.94±0.24,囊性大鼠为0.83±0.11。在这些年轻大鼠中,尽管存在囊性疾病,但肾小球滤过率或PAH最大分泌率并无显著差异。通过荧光显微镜检查发现,29个近端囊肿中有27个分泌了磺酰荧光素,这是一种由PAH系统转运的有机阴离子。对已分泌磺酰荧光素的浅表囊肿进行的透射电子显微镜检查显示,存在外观正常和分化不良的近端小管细胞。通过上游和下游蜡块分离出的浅表近端曲管或囊肿节段,在静脉输注PAH时未蓄积液体。采用固定微灌注技术,证实正常和囊性肾单位均有PAH分泌。得出的结论是,大多数近端囊性上皮细胞保留了分泌有机阴离子的能力。然而,有机阴离子的分泌似乎并未对大鼠肾囊肿内的液体蓄积产生任何实质性影响。