Pachymic acid attenuates lipopolysaccharides-induced acute kidney inju-ry by inhibiting inflammation and renal tubular epithelial cell apoptosis
10.3969/j.issn.1000-4718.2025.05.018
- VernacularTitle:茯苓酸通过抑制炎症和肾小管上皮细胞凋亡减轻脂多糖诱导的急性肾损伤
- Author:
Xun MO
1
;
Shanshan YU
;
Jing JIA
;
Yuting CHEN
;
Yulin PENG
;
Fang-fang WANG
;
Xiong YU
;
Rongyu CHEN
;
Wanlin TAN
;
Xiaoxiao XU
;
Luqun LIANG
;
Yuanyuan RUAN
;
Mingjun SHI
;
Yuanyuan WANG
;
Bing GUO
Author Information
1. 贵州医科大学基础医学院病理生理教研室,贵州省常见慢性疾病发病机制及药物研究重点实验室,贵州 安顺 561113;贵阳市第二人民医院,贵州 贵阳 550005
- Publication Type:Journal Article
- Keywords:
pachymic acid;
lipopolysaccharides;
acute kidney injury;
inflammatory factors;
apoptosis
- From:
Chinese Journal of Pathophysiology
2025;41(5):995-1005
- CountryChina
- Language:Chinese
-
Abstract:
AIM:To investigate the therapeutic effects and potential mechanism of pachymic acid(PA)on li-popolysaccharide(LPS)-induced acute kidney injury(AKI)in mice.METHODS:(1)Genes related to AKI were screened using the DAVID database.Core genes were identified by intersecting related genes and analyzed using Cyto-scape software.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analyses were performed through the DAVID database for the cross-targets.Molecular docking and activity assays were conducted on the primary core targets.(2)A total of 100 C57BL/6J mice were randomly divided into five groups:normal control(NC),model(LPS),solvent control(LPS+DMSO),and treatment groups(LPS+PA-10 and LPS+PA-20),with 20 mice in each group.The LPS-AKI model was established by intraperitoneal injection of 18 mg/kg LPS.The treatment groups received 10 mg/kg and 20 mg/kg PA,respectively,and the solvent control group was administered an equivalent dose of DMSO.Mice were euthanized 24 h after injection.Serum was collected for biochemical analysis,and Western blot was used to detect neutro-phil gelatinase-associated lipocalin(NGAL),kidney injury molecule-1(KIM-1),caspase-3,cleaved caspase-3,interleu-kin-1β(IL-1β),and monocyte chemoattractant protein-1(MCP-1)protein expression.RT-qPCR was employed to detect inflammatory factor mRNA levels.Molecular docking was used to simulate the optimal binding site of PA to caspase-3.En-zyme activity assays were performed to assess caspase protein activity,and renal lesions were observed via hematoxylin and eosin(HE)staining.Apoptosis was detected by TUNEL staining.RESULTS:(1)Thirty-one potential targets of PA against AKI were identified through network pharmacology.GO and KEGG enrichment analyses indicated that these tar-gets were primarily involved in immune response,inflammatory processes,apoptosis and survival,angiogenesis and hemo-dynamics,oxidative stress,and endoplasmic reticulum stress.Key targets included CASP3(caspase-3),PTGS2,BCL2,CCL2,and CYP219.(2)PA treatment improved renal function and reduced tubular epithelial injury.It significantly de-creased NGAL,KIM-1,and cleaved caspase-3 protein levels,as well as inflammatory factors TNF-α,IL-1β,and MCP-1 mRNA and protein expression.PA also reduced apoptosis of renal tubular epithelial cells.Enzyme activity assays and mo-lecular docking revealed that PA exerted its anti-apoptotic effect by directly binding to caspase-3,thereby inhibiting its ac-tivation by caspase-8.CONCLUSION:PA demonstrated a therapeutic effect in LPS-AKI,potentially through the inhibi-tion of inflammatory factor synthesis and release,as well as the inhibition of caspase-3 activation by caspase-8,reducing apoptosis in renal tubular epithelial cells.
