昆明医科大学学报2025，Vol.46Issue(6)：29-37,9.DOI:10.12259/j.issn.2095-610X.S20250604
丹参酮Ⅰ调控Wnt/β-catenin信号通路缓解大鼠脓毒症相关急性肾损伤
Tanshinone Ⅰ Alleviates Sepsis Associated Acute Kidney Injury in Rats by Regulating Wnt/β-catenin Signaling Pathway
摘要
Abstract
Objective To investigate the effect of Tan Ⅰ on SA-AKI in rats by mediating Wnt/β-catenin signaling pathway.Methods Sprague-Dawley rats were randomly divided into the following groups(n=8 per group,including 2 reserve animals per group):Sham,SA-AKI,SA-AKI+5 mg/kg Tan I,SA-AKI+10 mg/kg Tan I,SA-AKI+15 mg/kg Tan I(SA-AKI+Tan I),SA-AKI+salinomycin sodium(SS,Wnt signal inhibitor,SA-AKI+SS),SA-AKI+SS+Tan I,SA-AKI+laduviglusib(LG,Wnt signal activator,SA-AKI+LG),and SA-AKI+LG+Tan I.Rat SA-AKI model was induced by cecal ligation and puncture(CLP),with Tan I,SS,and LG administered via intraperitoneal injection.Hematoxylin-eosin and TUNEL staining were used to observe renal tissue pathological damage.Enzyme-linked immunosorbent assay was used to detect serum concentrations of neutrophil gelatinase-associated lipocalin(NGAL),IL-1β,IL-8,IL-6,and TNF-α.Creatinine(Cre)and blood urea nitrogen(BUN)kit were used to detect serum Cre and BUN concentrations.Western blot and immunofluorescence staining were used to detect the expression and fluorescence intensity of Wnt1,GSK3β,and β-catenin.Results Administration of Tan I at doses of 10 mg/kg and 15 mg/kg significantly attenuated renal injury in rats with SA-AKI(P<0.05),suppressed the levels of SA-AKI biomarkers NGAL,Cre,and BUN and pro-inflammatory cytokines(P<0.05),reduced apoptosis,and downregulated Wnt1 and GSK3β while upregulating β-catenin expression(P<0.05).Although Tan I at 5 mg/kg exhibited a modest protective effect against SA-AKI in rats,no statistically significant difference was observed compared to the sham group(P>0.05).SS weakened CLP-induced kidney injury and the production of inflammatory cytokines in rats(P<0.05),and LG further aggravated CLP-induced kidney injury in rats(P<0.05).Tan Ⅰ reversed the promoting effect of LG on kidney injury in SA-AKI rats(P<0.05).Conclusion Tan Ⅰ provides a protective effect on CLP-induced SA-AKI rat by inhibiting Wnt/β-catenin signaling pathway.关键词
脓毒症相关急性肾损伤/丹参酮Ⅰ/Wnt信号通路/肾功能/炎性细胞因子Key words
Sepsis associated acute kidney injury/Tanshinone Ⅰ/Wnt signaling pathway/Kidney function/Inflammatory cytokines分类
医药卫生引用本文复制引用
任靖宇,蒋兴鹏,李正超,文世媛,朱砂,茹金..丹参酮Ⅰ调控Wnt/β-catenin信号通路缓解大鼠脓毒症相关急性肾损伤[J].昆明医科大学学报,2025,46(6):29-37,9.基金项目
云南省科技厅-昆明医科大学应用基础研究联合专项基金(202101AY070001-238) （202101AY070001-238）
云南省呼吸系统疾病临床医学中心平台开放课题基金(2022LCZXKF-HX07) （2022LCZXKF-HX07）
