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灵芝酸通过抑制炎症和细胞凋亡预防肾缺血再灌注损伤。

Ganoderic Acids Prevent Renal Ischemia Reperfusion Injury by Inhibiting Inflammation and Apoptosis.

机构信息

State Key Laboratory of Natural and Biomimetic Drugs, Department of Pharmacology, School of Basic Medical Sciences, Peking University, Beijing 100191, China.

Fuzhou Institute of Green Valley Bio-Pharm Technology, Fuzhou 350002, China.

出版信息

Int J Mol Sci. 2021 Sep 23;22(19):10229. doi: 10.3390/ijms221910229.

Abstract

Renal ischemia reperfusion injury (RIRI) is one of the main causes of acute kidney injury (AKI), which can lead to acute renal failure. The development of RIRI is so complicated that it involves many factors such as inflammatory response, oxidative stress and cell apoptosis. Ganoderic acids (GAs), as one of the main pharmacological components of , have been reported to possess anti-inflammatory, antioxidant, and other pharmacological effects. The study is aimed to investigate the protective effect of GAs on RIRI and explore related underlying mechanisms. The mechanisms involved were assessed by a mouse RIRI model and a hypoxia/reoxygenation model. Compared with sham-operated group, renal dysfunction and morphological damages were relieved markedly in GAs-pretreatment group. GAs pretreatment could reduce the production of pro-inflammatory factors such as IL-6, COX-2 and iNOS induced by RIRI through inhibiting TLR4/MyD88/NF-kB signaling pathway. Furthermore, GAs reduced cell apoptosis via the decrease of the ratios of cleaved caspase-8 and cleaved caspase-3. The experimental results suggest that GAs prevent RIRI by alleviating tissue inflammation and apoptosis and might be developed as a candidate drug for preventing RIRI-induced AKI.

摘要

肾缺血再灌注损伤(RIRI)是急性肾损伤(AKI)的主要原因之一,可导致急性肾衰竭。RIRI 的发展非常复杂,涉及炎症反应、氧化应激和细胞凋亡等多种因素。灵芝酸(GAs)作为灵芝的主要药理成分之一,具有抗炎、抗氧化等多种药理作用。本研究旨在探讨 GAs 对 RIRI 的保护作用及其相关机制。通过建立小鼠 RIRI 模型和缺氧/复氧模型进行研究。与假手术组相比,GA 预处理组的肾功能和形态损伤明显缓解。GA 预处理通过抑制 TLR4/MyD88/NF-κB 信号通路,减少 RIRI 诱导的促炎因子(如 IL-6、COX-2 和 iNOS)的产生。此外,GA 通过降低裂解半胱天冬酶-8 和裂解半胱天冬酶-3 的比值来减少细胞凋亡。实验结果表明,GA 通过减轻组织炎症和细胞凋亡来预防 RIRI,可能被开发为预防 RIRI 诱导的 AKI 的候选药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab32/8508562/89ab1ab0d88f/ijms-22-10229-g001.jpg

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