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维生素 D 补充的体外抗炎作用在血液透析患者中可能变得模糊。

In vitro anti-inflammatory effects of vitamin D supplementation may be blurred in hemodialysis patients.

机构信息

Laboratorio de Nefrologia Experimental, Departamento de Patologia Basica, Universidade Federal do Parana, Curitiba, PR, BR.

Departamento de Medicina Interna, Divisao de Nefrologia, Universidade Federal do Parana, Curitiba, PR, BR.

出版信息

Clinics (Sao Paulo). 2021 Feb 22;76:e1821. doi: 10.6061/clinics/2021/e1821. eCollection 2021.

Abstract

OBJECTIVES

This study aimed to evaluate the potential anti-inflammatory effects of vitamin D supplementation under uremic conditions, both in vivo and in vitro, and its effects on the parameters of mineral metabolism.

METHODS

Thirty-two hemodialysis patients were randomly assigned to receive placebo (N=14) or cholecalciferol (N=18) for six months. Serum levels of calcium, phosphate, total alkaline phosphatase, intact parathyroid hormone (iPTH), and vitamin D were measured at baseline and after three and six months. The levels of fibroblast growth factor-23 (FGF-23), interleukin-1β (IL-1β), and high-sensitivity C-reactive protein (hs-CRP) were also measured at baseline and at six months. Human monocytes were used for in vitro experiments and treated with cholecalciferol (150 nM) and uremic serum. Cell viability, reactive oxygen species (ROS) production, and cathelicidin (CAMP) expression were evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, dichloro-dihydro-fluorescein diacetate assay, and real time-quantitative polymerase chain reaction, respectively.

RESULTS

Both patient groups were clinically and biochemically similar at baseline. After six months, the levels of vitamin D and iPTH were higher and lower, respectively, in the cholecalciferol group than in the placebo group (p<0.05). There was no significant difference between the parameters of mineral metabolism, such as IL-1β and hs-CRP levels, in both groups. Treatment with uremic serum lowered the monocyte viability (p<0.0001) and increased ROS production (p<0.01) and CAMP expression (p<0.05); these effects were counterbalanced by cholecalciferol treatment (p<0.05).

CONCLUSIONS

Thus, cholecalciferol supplementation is an efficient strategy to ameliorate hypovitaminosis D in hemodialysis patients, but its beneficial effects on the control of secondary hyperparathyroidism are relatively unclear. Even though cholecalciferol exhibited anti-inflammatory effects in vitro, its short-term supplementation was not effective in improving the inflammatory profile of patients on hemodialysis, as indicated by the IL-1β and hs-CRP levels.

摘要

目的

本研究旨在评估维生素 D 补充在尿毒症患者体内和体外的潜在抗炎作用,及其对矿物质代谢参数的影响。

方法

32 名血液透析患者被随机分为安慰剂组(N=14)或胆钙化醇组(N=18),接受为期 6 个月的治疗。在基线时以及治疗 3 个月和 6 个月后测量血清钙、磷、总碱性磷酸酶、全段甲状旁腺激素(iPTH)和维生素 D 水平。在基线和 6 个月时还测量了成纤维细胞生长因子 23(FGF-23)、白细胞介素-1β(IL-1β)和高敏 C 反应蛋白(hs-CRP)的水平。使用胆钙化醇(150 nM)和尿毒症血清处理人单核细胞进行体外实验。使用 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐测定法、二氯二氢荧光素二乙酸酯测定法和实时定量聚合酶链反应分别评估细胞活力、活性氧(ROS)产生和抗菌肽(CAMP)表达。

结果

两组患者在基线时临床和生化特征相似。6 个月后,与安慰剂组相比,胆钙化醇组的维生素 D 水平升高,iPTH 水平降低(p<0.05)。两组的矿物质代谢参数如 IL-1β 和 hs-CRP 水平均无显著差异。尿毒症血清处理降低单核细胞活力(p<0.0001),增加 ROS 产生(p<0.01)和 CAMP 表达(p<0.05);这些作用通过胆钙化醇处理得到平衡(p<0.05)。

结论

因此,胆钙化醇补充是改善血液透析患者维生素 D 缺乏的有效策略,但对控制继发性甲状旁腺功能亢进症的有益作用尚不清楚。尽管胆钙化醇在体外表现出抗炎作用,但在短期内补充胆钙化醇并不能改善血液透析患者的炎症特征,这可以从 IL-1β 和 hs-CRP 水平看出。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3827/7885853/f18d6dd7c9f9/cln-76-e1821-g001.jpg

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