雷帕霉素为基础的免疫抑制方案对大鼠肾脏水通道蛋白 1、2、3 和 4 表达的长期影响。

The long-term effects of rapamycin-based immunosuppressive protocols on the expression of renal aquaporins 1, 2, 3 and 4 water channels in rats.

机构信息

Department of Histology and Developmental Biology, Pomeranian Medical University, Szczecin, Poland.

Department of Physiology, Cytobiology and Proteomics, West Pomeranian University of Technology, Szczecin, Poland.

出版信息

Histol Histopathol. 2021 Apr;36(4):459-474. doi: 10.14670/HH-18-321. Epub 2021 Feb 26.

Abstract

BACKGROUND

To this day, the effect of multi-drug immunosuppressive protocols on renal expression of AQPs is unknown. This study aimed to determine the influence of rapamycin-based multi-drug immunosuppressive regimens on the expression of aquaporins (AQPs) 1, 2, 3, and 4 in the rat kidney.

METHODS

For 6 months, 24 male Wistar rats were administered immunosuppressants, according to the three-drug protocols used in patients after organ transplantation. The rats were divided into four groups: the control group, the TRP group (tacrolimus, rapamycin, prednisone), the CRP group (cyclosporine A, rapamycin, prednisone), and the MRP group (mycophenolate mofetil, rapamycin, prednisone). Selected red cell indices and total calcium were measured in the blood of rats and quantitative analysis of AQP1, AQP2, AQP3 and AQP4 immunoexpression in the kidneys were performed.

RESULTS

In the TRP and CRP groups, a mild increase of mean corpuscular hemoglobin concentration, hematocrit and total calcium were observed. Moreover, decreased expression of AQP1-4 was found in all experimental groups, with the highest decrease in the CRP group.

CONCLUSIONS

The long-term immunosuppressive treatment using multi-drug protocols decreased AQP1-4 expressions in renal tubules, possibly leading to impaired urine-concentrating ability in rat.

摘要

背景

时至今日,多药物免疫抑制方案对肾脏水通道蛋白(AQP)表达的影响仍不清楚。本研究旨在探讨雷帕霉素为基础的多药物免疫抑制方案对大鼠肾脏水通道蛋白(AQP)1、2、3 和 4 表达的影响。

方法

24 只雄性 Wistar 大鼠接受免疫抑制剂治疗,用药方案为器官移植患者使用的三药方案。大鼠分为四组:对照组、TRP 组(他克莫司、雷帕霉素、泼尼松)、CRP 组(环孢素 A、雷帕霉素、泼尼松)和 MRP 组(霉酚酸酯、雷帕霉素、泼尼松)。检测大鼠血液中的红细胞指数和总钙,并对肾脏 AQP1、AQP2、AQP3 和 AQP4 免疫表达进行定量分析。

结果

TRP 组和 CRP 组的平均红细胞血红蛋白浓度、红细胞压积和总钙略有增加。此外,所有实验组的 AQP1-4 表达均下降,CRP 组下降最明显。

结论

长期多药物免疫抑制治疗降低了肾小管中 AQP1-4 的表达,可能导致大鼠尿液浓缩能力受损。

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