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丝裂原活化蛋白激酶、脂质运载蛋白-2和Fas在白藜芦醇脂质体对异丙肾上腺素诱导的肾损伤的保护作用中的意义。

Implication of MAPK, Lipocalin-2, and Fas in the protective action of liposomal resveratrol against isoproterenol-induced kidney injury.

作者信息

Alhusaini Ahlam M, Alshehri Samiyah M, Sarawi Wedad S, Alghibiwi Hanan K, Alturaif Sumayya A, Al Khbiah Reema A, Alali Shog M, Alsaif Shaikha M, Alsultan Ebtesam N, Hasan Iman H

机构信息

Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O Box 22452, Riyadh 11495, Saudi Arabia.

Pharm D Program, College of Pharmacy, King Saud University, P.O Box 22452, Riyadh 11495, Saudi Arabia.

出版信息

Saudi Pharm J. 2024 Jan;32(1):101907. doi: 10.1016/j.jsps.2023.101907. Epub 2023 Dec 10.

Abstract

BACKGROUND AND OBJECTIVE

Isoproterenol (ISO) is a non-selective β-adrenergic receptor agonist. It can be used to treat bradycardia and cardiogenic shock. Despite its usefulness, the overstimulation of β-receptors by ISO can cause "cardiorenal syndrome," a term used to describe heart and kidney damage. Resveratrol (RES), a natural polyphenol, has marked anti-inflammatory and antioxidant activities. The present work was designed to study the protective efficacy of liposomal resveratrol (L-RES) against ISO-induced kidney injury.

MATERIALS AND METHODS

The kidney injury was induced in rats by administering ISO (50 mg/kg, s.c.) twice a week for 2 weeks. RES and L-RES were administered at a dose (20 mg/kg/ day, p.o.) along with ISO for 2 weeks. Inflammatory and apoptotic biomarkers were analyzed, which were validated using histochemical analysis.

RESULTS

ISO caused renal dysfunction, which manifested as elevated urea, creatinine and uric acid, besides cystatin c and MAPK protein overexpression. In addition, ISO induced gene expression of Fas and lipocalin-2 and provoked genomic DNA fragmentation in renal tissues as compared with the control group. Histological examination confirmed morphological alterations of the kidney tissues obtained from the ISO group. Concurrent treatment of either RES or L-RES with ISO significantly ameliorated kidney damage as demonstrated by the improvement of all measured parameters with the best results for L-RES. The histopathological findings were correlated with the above biochemical parameters.

CONCLUSION

L-RES could be a promising approach for the prevention of kidney injury induced by ISO, most likely via the downregulation of MAPK, cystatin c, Fas, and lipocalin-2.

摘要

背景与目的

异丙肾上腺素(ISO)是一种非选择性β-肾上腺素能受体激动剂。它可用于治疗心动过缓和心源性休克。尽管其有用性,但ISO对β受体的过度刺激可导致“心肾综合征”,这是一个用于描述心脏和肾脏损伤的术语。白藜芦醇(RES)是一种天然多酚,具有显著的抗炎和抗氧化活性。本研究旨在探讨脂质体白藜芦醇(L-RES)对ISO诱导的肾损伤的保护作用。

材料与方法

通过每周两次皮下注射ISO(50mg/kg),连续2周诱导大鼠肾损伤。RES和L-RES以剂量(20mg/kg/天,口服)与ISO一起给药2周。分析炎症和凋亡生物标志物,并使用组织化学分析进行验证。

结果

ISO导致肾功能障碍,表现为尿素、肌酐和尿酸升高,此外胱抑素c和MAPK蛋白过度表达。此外,与对照组相比,ISO诱导肾组织中Fas和lipocalin-2的基因表达,并引发基因组DNA片段化。组织学检查证实了ISO组肾脏组织的形态学改变。RES或L-RES与ISO同时治疗显著改善了肾损伤,所有测量参数均有改善,L-RES效果最佳。组织病理学结果与上述生化参数相关。

结论

L-RES可能是预防ISO诱导的肾损伤的一种有前景的方法,最有可能是通过下调MAPK、胱抑素c、Fas和lipocalin-2来实现。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a29e/10764257/c17a22e41632/gr1.jpg

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