西南医科大学学报2026，Vol.49Issue(5)：606-615,10.DOI:10.3969/j.issn.2096-3351.2026.05.007
新型亲环蛋白抑制剂JAK-103对腺嘌呤诱导的小鼠慢性肾损伤的保护作用
Protective Effects of the Novel Cyclophilin Inhibitor JAK-103 on Adenine-Induced Chronic Kidney Injury in Mice
摘要
Abstract
Objective To investigate the effects of JAK-103,a novel cyclophilin inhibitor,on the adenine-induced mouse model of chronic kidney injury and preliminarily explore its underlying mechanism.Methods Sixty C57BL/6J mice were randomly divided into a blank control group(Control group,n=10)and a model group(n=50).The model group was intragastrically adminis-tered adenine(90 mg·kg-1·d-1)for 7 consecutive days to induce a chronic kidney injury model.Subsequently,the 50 mice in the model group were further divided into a model control group(Model group),a dapagliflozin group,and three dose groups of JAK-103(low,medium,and high doses)with 10 mice per group for drug treatment.Meanwhile,maintenance doses of adenine(90 mg·kg-1·d-1)were intragastrically administered on days 9,11,13,and 21 after modeling.After 21 days of administration,urine samples were collected to measure protein excretion;mice were euthanized by CO₂ inhalation;blood samples were harvested to detect serum levels of urea nitrogen and creatinine;bilateral kidneys were excised and weighed to calculate the organ index;the expression levels of TNF-α,IL-34,α-smooth muscle actin(α-SMA)and Collagen I were analyzed by immunohistochemistry(IHC),and histopathological examina-tion was performed via HE and Masson's trichrome staining.The levels of IL-6,TGF-β,NF-κB and Caspase-3 were detected by ELISA,and the oxidative stress indexes(GSH,SOD,and MDA)in renal tissue were simultaneously determined.Results JAK-103 exhibited a significant renoprotective effect.Treatment with JAK-103 at 20,60 and 180 mg/kg significantly improved renal function in model mice;serum CRE levels in the medium and high-dose JAK-103 groups were markedly lower than those in the model group(P<0.05).JAK-103 also reduced the kidney index to a certain extent,and the medium-and high-dose groups significantly decreased the HE and Masson staining scores(P<0.05)and reduced the area of renal interstitial fibrosis.It significantly down-regulated the expres-sion of inflammation and fibrosis-related factors,and improved the oxidative stress status of renal tissue.Conclusion JAK-103 exerts a protective effect against adenine-induced chronic kidney injury in mice.This effect is associated with the inhibition of renal inflamma-tion and the alleviation of renal interstitial fibrosis.It can effectively improve renal function,mitigate renal histopathological damage,and delay the pathological progression of chronic kidney injury.关键词
亲环蛋白/慢性肾病/肿瘤坏死因子-α/白细胞介素-34Key words
Cyclophilin/Chronic kidney disease/Tumor necrosis factor-α/Interleukin-34分类
医药卫生引用本文复制引用
陈成,张文静,侯久文,徐铭泽,杜建军,梅其炳,曾静..新型亲环蛋白抑制剂JAK-103对腺嘌呤诱导的小鼠慢性肾损伤的保护作用[J].西南医科大学学报,2026,49(5):606-615,10.基金项目
泸州新药评价研究中心合作项目(PD20240720) （PD20240720）
