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首页> 外文期刊>American Journal of Physiology >Long-term treatment with cyclosporine decreases aquaporins and urea transporters in the rat kidney.
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Long-term treatment with cyclosporine decreases aquaporins and urea transporters in the rat kidney.

机译：长期使用环孢霉素治疗可降低大鼠肾脏中水通道蛋白和尿素转运蛋白的水平。

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The aim of this study was to evaluate the long-term effects of cyclosporine (CsA) treatment on urinary concentration ability. Rats were treated daily for 4 wk with vehicle (VH; olive oil, 1 ml/kg sc) or CsA (15 mg/kg sc). The influence of CsA on the kidney's ability to concentrate urine was evaluated using functional parameters and expression of aquaporins (AQP1-4) and of urea transporters (UT-A-1-3, and UT-B). Plasma vasopressin levels and the associated signal pathway were evaluated, and the effect of vasopressin infusion on urine concentration was observed in VH- and CsA-treated rats. Toxic effects of CsA on tubular cells in the medulla as well as the cortex were evaluated with aldose reductase (AR), Na-K-ATPase-alpha(1) expression, and by determining the number of terminal transferase-mediated dUTP nick end-labeling (TUNEL)-positive cells. Long-term CsA treatment increased urine volume and fractional excretion of sodium and decreased urine osmolality and free-water reabsorption compared with VH-treated rats. These functional changes were accompanied by decreases in the expression of AQP (1-4) and UT (UT-A2, -A3, and UT-B), although there was no change in AQP2 in the cortex and outer medulla and UT-A1 in the inner medulla (IM). Plasma vasopressin levels were not significantly different between two groups, but infusion of vasopressin restored CsA-induced impairment of urine concentration. cAMP levels and Gsalpha protein expression were significantly reduced in CsA-treated rat kidneys compared with VH-treated rat kidneys. CsA treatment decreased the expression of AR and Na-K-ATPase-alpha(1) and increased the number of TUNEL-positive renal tubular cells in both the cortex and medulla. Moreover, the number of TUNEL-positive cells correlated with AQP2 or UT-A3) expression within the IM. In conclusion, CsA treatment impairs urine-concentrating ability by decreasing AQP and UT expression. Apoptotic cell death within the IM at least partially accounts for the CsA-induced urinary concentration defect.
机译：这项研究的目的是评估环孢素（CsA）治疗对尿液浓缩能力的长期影响。每天用赋形剂（VH;橄榄油，1 ml / kg sc）或CsA（15 mg / kg sc）治疗大鼠4 wk。使用功能参数和水通道蛋白（AQP1-4）和尿素转运蛋白（UT-A-1-3和UT-B）的表达来评估CsA对肾脏浓缩尿液能力的影响。评价了血浆加压素水平和相关的信号通路，并在VH和CsA处理的大鼠中观察了加压素输注对尿液浓度的影响。用醛糖还原酶（AR），Na-K-ATPase-alpha（1）表达并通过确定末端转移酶介导的dUTP缺口末端的数量来评估CsA对髓质和皮质中肾小管细胞的毒性作用标记（TUNEL）阳性细胞。与经VH处理的大鼠相比，长期CsA处理可增加尿量和钠的部分排泄，并降低尿渗透压和自由水的重吸收。这些功能性变化伴随着AQP（1-4）和UT（UT-A2，-A3和UT-B）的表达降低，尽管皮层，外延髓和UT-A1中的AQP2没有变化在内侧髓质（IM）中。两组之间的血浆加压素水平无明显差异，但输注加压素可恢复CsA诱导的尿液浓度受损。与VH处理的大鼠肾脏相比，CsA处理的大鼠肾脏中的cAMP水平和Gsalpha蛋白表达显着降低。 CsA处理降低了皮质和髓质中AR和Na-K-ATPase-alpha（1）的表达，并增加了TUNEL阳性肾小管细胞的数量。此外，与IM中的AQP2或UT-A3）表达相关的TUNEL阳性细胞数量。总之，CsA治疗可通过降低AQP和UT表达来削弱尿液浓缩能力。 IM中的凋亡细胞死亡至少部分地解释了CsA诱导的尿液浓度缺陷。

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