中国中西医结合杂志2025，Vol.45Issue(6)：699-705,7.DOI:10.7661/j.cjim.20250411.005
姜黄素调控线粒体凋亡改善Wilson病铜负荷大鼠肝纤维化
Curcumin Regulates Mitochondrial Apoptosis Pathway to Alleviate Liver Fibrosis in Copper-Loaden Rats with Wilson Disease
摘要
Abstract
Objective To investigate whether curcumin can regulate mitochondrial apoptosis pathway to alleviate liver fibrosis in copper-laden rats with Wilson disease.Methods Thirty Wistar rats were randomly divided into the normal,model,curcumin middle-dose and high-dose groups.Except for the normal group,the other groups were established by feeding with copper sulfate chow(1 g·kg-1)and copper sulfate water(0.185％)for 12 weeks.In addition,curcumin middle-dose and high-dose groups were given 100 and 200 mg·kg-1·d-1 of curcumin by gavage for 6 weeks,respectively.Serum aminotransferases(ALT and AST)were detected by microplate assay;hepatic copper levels was detected by copper ion kit;hepatic copper salts and fibrosis deposition were observed by histopathological staining;ultrastructure was observed by transmission electron microscopy;hepatic Na+-K+-ATPase activity was detected by fixed phosphorus assay;reactive oxygen species(ROS)and mitochondrial membrane potential(MMP)were detected by flow cytometry.Finally,Western Blot were used to observe the expressions of B-cell lymphoma-2(Bcl-2),B-cell lymphoma-2 associated X protein(Bax)and cysteinyl aspartate specific proteinase-3(Caspase-3).Results Compared with the normal group,the model group exhibited significantly higher levels of serum ALT and AST(P＜0.01),significant liver structural damage with proliferated collagen fibers,significantly increased deposition of copper salts in liver tissue(P＜0.01),decreased activity of Na+-K+-ATPase,increased ROS,and dissipated MMP in liver tissue(P＜0.01);significantly reduced number of mitochondria with sparse and unclear cristae structure,up-regulated expressions of Bax and Caspase-3,and down-regulated expression of Bcl-2(P＜0.01).In contrast,after intervention with curcumin at middle or high dose,the model rats showed significantly decreased serum ALT and AST level(P＜0.01);partial restoration of liver structure with reduced collagen fibers;significantly reduced deposition of copper salts in liver tissue(P＜0.01);increased activity of Na+-K+-ATPase,decreased ROS,and increased MMP in liver tissue(P＜0.01);increased number of mitochondria with partial restoration of cristae structure;down-regulated expressions of Bax and Caspase-3,and up-regulated expression of Bcl-2 in liver tissue(P＜0.01).Conclusion Curcumin can reduce hepatic copper deposition,improve hepatic mitochondrial function,inhibit apoptosis via mitochondria-related pathway,and alleviate hepatic fibrosis in copper-loaded rats.关键词
Wilson病/肝纤维化/姜黄素/线粒体/凋亡/中药提取物Key words
Wilson disease/liver fibrosis/curcumin/mitochondria/apoptosis/extracts of Chinese medicine引用本文复制引用
杨悦,杨文明,何伟,杨玉龙,席虎,郝文杰,何望生..姜黄素调控线粒体凋亡改善Wilson病铜负荷大鼠肝纤维化[J].中国中西医结合杂志,2025,45(6):699-705,7.基金项目
国家自然科学基金区域创新发展联合基金项目(No.U22A20366) （No.U22A20366）
国家自然科学基金面上项目(No.81973825) （No.81973825）
国家中医药传承创新中心项目(No.2022366) （No.2022366）
安徽高校协同创新项目(No.GXXT-2020-025) （No.GXXT-2020-025）
安徽高校自然科学研究项目(No.KJ2021A0553) （No.KJ2021A0553）
