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Self-developed NF-kappa B inhibitor 270 protects against LPS-induced acute kidney injury and lung injury through improving inflammation

文献类型：期刊论文

作者Yu, Yan-yan1; Li, Xiang-qian1; Hu, Wen-peng1; Cu, Shi-chao3; Dai, Jia-jia1; Gao, Ya-nan1; Zhang, Yi-ting1; Bai, Xiao-yi1; Shi, Da-yong1,2
刊名BIOMEDICINE & PHARMACOTHERAPY
出版日期2022-03-01
卷号147页码:12
ISSN号0753-3322
关键词AKI ALI Inflammation NF-kappa B inhibitor 270
DOI10.1016/j.biopha.2022.112615
通讯作者Shi, Da-yong(shidayong@sdu.edu.cn)
英文摘要Sepsis-induced acute kidney injury (AKI) and acute lung injury (ALI) have high morbidity and mortality, with no effective clinically available drugs. Anti-inflammation is effective strategy in the therapy of AKI and ALI. NF-kappa B is a target for the development of anti-inflammatory agents. The purpose of the study is to evaluate the effect of 270, self-developed NF-kappa B inhibitor, in LPS-induced AKI and ALI. LPS-induced macrophages were used to examine the anti-inflammation activity of 270 in vitro. Sepsis-induced AKI and ALI mice models were established by intraperitoneal injection of LPS (10 mg/kg) for 24 h. Oral administration 270 for 14 days before LPS stimulation. Plasma, kidney and lung tissues were collected and used for histopathology, biochemical assay, ELISA, RT-PCR, and western blot analyses. In vitro, we showed that 270 suppressed the inflammation response in LPS-induced RAW 264.7 macrophages and bone marrow derived macrophages. In vivo, we found that 270 ameliorated LPS-induced AKI and ALI, as evidenced by improving various pathological changes, reducing the expression of pro-inflammation genes, blocking the activation of NF-kappa B and JNK pathways, attenuating the elevated myeloperoxidase (MPO) activity and malondialdehyde (MDA) content, ameliorating the activated ER stress, reversing the inhibition effect on autophagy in kidney and lung tissues, and alleviating the enhanced plasma level of creatinine (Crea), blood urea nitrogen (BUN) and pro-inflammation cytokines. Our investigations provides evidence that NF-kappa B inhibitor 270 is a potential drug that against LPS-induced AKI and ALI in the future.
WOS关键词BROMOPHENOLS ; AUTOPHAGY ; STRESS ; MAPK ; MICE
资助项目Certificate of China Postdoctoral Science Foundation[2019M662374] ; Fundamental Research Funds of Shandong University[2020GN033] ; National Natural Science Foundation of China[82003787] ; Shandong Provincial Natural Science Foundation[ZR2020QH364]
WOS研究方向Research & Experimental Medicine ; Pharmacology & Pharmacy
语种英语
出版者ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
WOS记录号WOS:000744628000005
源URL[http://119.78.100.183/handle/2S10ELR8/300580]  
专题新药研究国家重点实验室
通讯作者Shi, Da-yong
作者单位1.Shandong Univ, Inst Microbial Technol, State Key Lab Microbial Technol, Qingdao 266200, Peoples R China
2.Qingdao Natl Lab Marine Sci & Technol, Lab Marine Drugs & Bioprod, Qingdao 266071, Peoples R China
3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai, Peoples R China
推荐引用方式
GB/T 7714		 Yu, Yan-yan,Li, Xiang-qian,Hu, Wen-peng,et al. Self-developed NF-kappa B inhibitor 270 protects against LPS-induced acute kidney injury and lung injury through improving inflammation[J]. BIOMEDICINE & PHARMACOTHERAPY,2022,147:12.
APA Yu, Yan-yan.,Li, Xiang-qian.,Hu, Wen-peng.,Cu, Shi-chao.,Dai, Jia-jia.,...&Shi, Da-yong.(2022).Self-developed NF-kappa B inhibitor 270 protects against LPS-induced acute kidney injury and lung injury through improving inflammation.BIOMEDICINE & PHARMACOTHERAPY,147,12.
MLA Yu, Yan-yan,et al."Self-developed NF-kappa B inhibitor 270 protects against LPS-induced acute kidney injury and lung injury through improving inflammation".BIOMEDICINE & PHARMACOTHERAPY 147(2022):12.

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来源：上海药物研究所

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