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首页> 外文期刊>Life sciences >Mapping the time-dependent effects of paricalcitol on serum calcium, phosphorus and parathyroid hormone levels in 5/6 nephrectomized uremic rats
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Mapping the time-dependent effects of paricalcitol on serum calcium, phosphorus and parathyroid hormone levels in 5/6 nephrectomized uremic rats

机译：绘制帕立骨化醇对5/6肾切除的尿毒症大鼠血清钙，磷和甲状旁腺激素水平的时间依赖性作用图

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Aims To investigate whether the frequency of monitoring paricalcitol's impact on serum calcium (Ca), phosphorus and PTH in current clinical practice is sufficient by mapping the time-dependent effects of paricalcitol on these parameters. Main methods The 5/6 nephrectomized (NX) male, Sprague-Dawley rats with established uremia were treated with vehicle or paricalcitol (0.16 μg/kg, i.p., 3 ×/week). On Day 0 (before treatment), Days 12 and 13 after treatment, and also at 0, 1, 4, 8, 16, 24 h after the last dosing, blood and small intestine samples were collected. Key findings Serum creatinine and blood urea nitrogen levels were significantly elevated in 5/6 NX rats. Significant increases were observed in serum Ca while PTH decreased by > 90% when the parameters were determined at 12 or 13 days after paricalcitol dosing. Paricalcitol caused a step-wise increase in serum Ca levels at 1-24 h following dosing, reduced serum PTH levels with PTH values ranging from 1.06 ± 0.06 to 26.7 ± 25.7 pg/ml (vs. 152 ± 15 pg/ml in Sham rats), but did not affect serum phosphorus in a time-dependent manner. Consistent with the serum Ca data, paricalcitol significantly induced the intestinal expression of Calb3 and TRPV6, genes involved in intestinal Ca transport, and also significantly induced the intestinal calcium absorption. Significance Our results suggest that the frequency of monitoring paricalcitol's effect on serum Ca, phosphorus and PTH in current clinical practice seems adequate. Additional clinical trials may be needed to resolve the inconsistent clinical observations about the impact of paricalcitol on serum Ca.
机译：目的通过绘制帕立骨化醇对这些参数的时间依赖性影响，以调查当前临床实践中监测帕立骨化醇对血清钙（Ca），磷和PTH的影响频率是否足够。主要方法对5/6肾切除的雄性Sprague-Dawley大鼠（已建立尿毒症）用媒介物或paricalcitol（0.16μg/ kg，腹腔注射，每周3次）治疗。在第0天（治疗前），治疗后第12天和第13天，以及最后一次给药后的0、1、4、8、16、24小时，收集血液和小肠样品。重要发现5/6 NX大鼠的血清肌酐和血液尿素氮水平显着升高。当在paricalcitol给药后第12或13天确定参数时，血清Ca显着增加，而PTH降低> 90％。剂量后1-24小时，帕立骨化醇引起血清Ca水平逐步升高，血清PTH降低，PTH值范围从1.06±0.06到26.7±25.7 pg / ml（与Sham大鼠的152±15 pg / ml相比） ），但不会以时间依赖性方式影响血清磷。与血清Ca数据一致，paricalcitol显着诱导了Calb3和TRPV6（参与肠道Ca转运的基因）的肠道表达，也显着诱导了肠道钙的吸收。意义我们的结果表明，在当前临床实践中监测帕立骨化醇对血清Ca，磷和PTH的影响的频率似乎是足够的。可能需要其他临床试验来解决有关paricalcitol对血清Ca的影响的不一致的临床观察结果。

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