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阿托伐他汀通过上调内源性硫化氢来防止对比剂诱导的急性肾损伤。

Atorvastatin protects against contrast-induced acute kidney injury via upregulation of endogenous hydrogen sulfide.

机构信息

Department of Nephrology, Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.

Department of Medical Genetics, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.

出版信息

Ren Fail. 2020 Nov;42(1):270-281. doi: 10.1080/0886022X.2020.1740098.

DOI:10.1080/0886022X.2020.1740098
PMID:33685337
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7144258/
Abstract

BACKGROUND

Contrast-induced acute kidney injury (CIAKI) is the third leading cause of acute renal failure in hospitalized patients. This study was aimed to investigate whether atorvastatin could upregulate the expression of hydrogen sulfide (HS) and hence protect against CIAKI.

METHODS

We treated male rats and NRK-52E cells by iopromide to establish and models of CIAKI. Pretreatment with atorvastatin was given in CIAKI rats to investigate its effect on CIAKI. We collected serum and urine samples to detect renal function. We obtained kidney tissue for histological analysis and detection of protein concentration. We tested the serum concentration of HS and renal expression of two HS synthetases [cystathionine γ-lyase (CSE) and cystathionine-β synthase (CBS)]. NaHS was pretreated in NRK-52E cells to testify its underlying effect on contrast-induced injury.

RESULTS

Atorvastatin significantly ameliorated renal dysfunction and morphological changes in CIAKI rats, as well as inflammation, apoptosis, and excessive oxidative stress. Atorvastatin also markedly increased the serum concentration of HS and renal expression of CSE and CBS. Moreover, pretreatment with NaHS in NRK-52E cells considerably attenuated contrast-induced cell death and inflammation.

CONCLUSION

Atorvastatin protects against CIAKI  upregulation of endogenous hydrogen sulfide.

摘要

背景

对比剂诱导的急性肾损伤(CIAKI)是住院患者急性肾衰竭的第三大原因。本研究旨在探讨阿托伐他汀是否可以上调硫化氢(HS)的表达,从而预防 CIAKI。

方法

我们用碘普罗胺处理雄性大鼠和 NRK-52E 细胞,建立 CIAKI 大鼠和细胞模型。用阿托伐他汀预处理 CIAKI 大鼠,以观察其对 CIAKI 的作用。收集血清和尿液样本检测肾功能。获取肾组织进行组织学分析和蛋白浓度检测。检测 HS 血清浓度和两种 HS 合酶(胱硫醚γ-裂解酶(CSE)和胱硫醚-β 合酶(CBS))在肾脏中的表达。用 NaHS 预处理 NRK-52E 细胞,以验证其对对比剂诱导损伤的潜在作用。

结果

阿托伐他汀显著改善 CIAKI 大鼠的肾功能和形态变化,以及炎症、细胞凋亡和过度氧化应激。阿托伐他汀还显著增加了 HS 的血清浓度和 CSE 和 CBS 在肾脏中的表达。此外,NRK-52E 细胞中 NaHS 的预处理可显著减轻对比剂诱导的细胞死亡和炎症。

结论

阿托伐他汀通过上调内源性硫化氢来保护 CIAKI。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e241/7144258/d0e6b402cb37/IRNF_A_1740098_F0009_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e241/7144258/dc0f65ef854e/IRNF_A_1740098_F0001_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e241/7144258/61e038e3170b/IRNF_A_1740098_F0002_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e241/7144258/f143c39c588b/IRNF_A_1740098_F0003_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e241/7144258/b6a5ee0087ae/IRNF_A_1740098_F0004_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e241/7144258/d45f427a7fa6/IRNF_A_1740098_F0005_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e241/7144258/f3db99be57a4/IRNF_A_1740098_F0006_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e241/7144258/83ef2c249e47/IRNF_A_1740098_F0007_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e241/7144258/b7ebdd1f2a6a/IRNF_A_1740098_F0008_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e241/7144258/d0e6b402cb37/IRNF_A_1740098_F0009_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e241/7144258/dc0f65ef854e/IRNF_A_1740098_F0001_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e241/7144258/61e038e3170b/IRNF_A_1740098_F0002_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e241/7144258/f143c39c588b/IRNF_A_1740098_F0003_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e241/7144258/b6a5ee0087ae/IRNF_A_1740098_F0004_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e241/7144258/d45f427a7fa6/IRNF_A_1740098_F0005_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e241/7144258/f3db99be57a4/IRNF_A_1740098_F0006_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e241/7144258/83ef2c249e47/IRNF_A_1740098_F0007_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e241/7144258/b7ebdd1f2a6a/IRNF_A_1740098_F0008_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e241/7144258/d0e6b402cb37/IRNF_A_1740098_F0009_B.jpg

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