全面研究地塞米松在正常和病理肾脏条件下对白蛋白生物合成的影响。

Comprehensive study of dexamethasone on albumin biogenesis during normal and pathological renal conditions.

机构信息

School of Pharmacy, Jiangxi University of Traditional Chinese Medicine, Nanchang, China.

Pharmacology Laboratory, State Key Laboratory of Innovative Drugs and Efficient Energy-Saving Pharmaceutical Equipment, Nanchang, China.

出版信息

Pharm Biol. 2020 Dec;58(1):1252-1262. doi: 10.1080/13880209.2020.1855214.

CONTEXT

Dexamethasone (DXM) has an anti-immunoinflammatory effect, and is often used in acute kidney injury (AKI). However, the effects of DXM on albumin (ALB) have not been fully studied.

OBJECTIVE

To investigate the effects of DXM on ALB production and renal function.

MATERIALS AND METHODS

Male Wistar rats were divided into normal and DXM groups (0.25, 0.5, 1 mg/kg for 5 days) ( = 15) for a dose-dependent study. Rats were divided into normal group and DXM groups (0.5 mg/kg for 3, 5, 7 days) ( = 9) for a time-dependent study. In AKI experiment, rats were divided into normal (saline), cisplatin (CP, 5 mg/kg, i.v.), CP + DXM groups (0.25, 0.5 and 1 mg/kg, i.m.) ( = 16). The blood and the organs were isolated for analysis.

RESULTS

In normal, serum ALB (sALB) and serum total protein (sTP) increased in DXM group with sALB increased 19.8-32.2% (from small to large dosages); and 30.2-32.5.6% (from 3 to 7 days of DXM); sTP 15.7-22.6% and 14.2-24.3%; urine ALB (uALB) 31.5-392.3%, and 1047.2-1390.8%; urine TP (uTP) 0.68-173.1% and 98.0-504.9%, compared with normal groups. DXM increased the mRNA expression of and , suppressing podocin. In AKI, DXM decreased serum BUN (53.7%), serum Cre (73.4%), sALB (30.0%), sTP (18.7%), uALB (74.5%), uTP (449.3%), rescuing the suppressed podocin in kidney.

CONCLUSIONS

DXM acts on and and promotes ALB production. This finding helps to evaluate the rationale of DXM for kidney injury.

背景

地塞米松（DXM）具有抗炎免疫作用，常用于急性肾损伤（AKI）。然而，DXM 对白蛋白（ALB）的影响尚未完全研究。

目的

研究 DXM 对 ALB 产生和肾功能的影响。

材料和方法

雄性 Wistar 大鼠分为正常组和 DXM 组（0.25、0.5、1mg/kg，5 天）（n=15）进行剂量依赖性研究。大鼠分为正常组和 DXM 组（0.5mg/kg，3、5、7 天）（n=9）进行时间依赖性研究。在 AKI 实验中，大鼠分为正常组（生理盐水）、顺铂（CP，5mg/kg，iv.）、CP+DXM 组（0.25、0.5 和 1mg/kg，im.）（n=16）。分离血液和器官进行分析。

结果

在正常组中，血清 ALB（sALB）和血清总蛋白（sTP）在 DXM 组中增加，sALB 增加 19.8-32.2%（从小剂量到大剂量）；30.2-32.5.6%（从 3 天到 7 天 DXM）；sTP 增加 15.7-22.6%和 14.2-24.3%；尿 ALB（uALB）增加 31.5-392.3%和 1047.2-1390.8%；尿总蛋白（uTP）增加 0.68-173.1%和 98.0-504.9%，与正常组相比。DXM 增加了和的 mRNA 表达，抑制了足细胞中的 podocin。在 AKI 中，DXM 降低了血清 BUN（53.7%）、血清 Cre（73.4%）、sALB（30.0%）、sTP（18.7%）、uALB（74.5%）、uTP（449.3%），挽救了肾脏中受抑制的 podocin。