南方医科大学学报2024，Vol.44Issue(11)：2063-2073,11.DOI:10.12122/j.issn.1673-4254.2024.11.02
肝豆补肾汤通过激活ERK信号通路减少Wilson病TX小鼠异常精子生成并促进生精细胞增殖
Gandou Bushen Decoction improves spermatogenesis and promotes spermatogenic cell proliferation in Wilson disease TX mice by activating testicular ERK signaling pathway
摘要
Abstract
Objective To investigate the therapeutic mechanism of Gandou Bushen Decoction(GDBSD)for improving reproductive disorders in male mouse models of Wilson disease(WD).Methods Sixty male homozygous TX mice were randomized equally into 4 groups and treated with daily gavage of saline(WD model group),penicillamine(0.09 g/kg),or GDBSD(0.2 mL/10 g),or with intraperitoneal injection of U0126(20 mg/kg)in addition to GDBSD gavage,with 15 male DL mice as control.After 4 weeks of treatment,copper content in testicular tissue of the mice was detected,and histopathology of the testes and epididymis was examined using HE staining and electron microscopy.TUNEL staining was used to identify apoptotic cells in the testes.The protein expressions of Bcl-2,Cytc,caspase-3,ERK,and p-ERK in the testicular tissue were evaluated with Western blotting,and BrdU-positive cells were detected with immunohistochemical labeling.Sperm density,viability,malformation rate and fertility levels of male mice were studied.Results Treatment with penicillamine and GDBSD obviously improved pathological changes of the testis,increased sperm density and motility,lowered sperm abnormality rate,fertility levels and increased testicular JOHNSEN score of TK mice,but the therapeutic effect of GDBSD was blocked by U0126.GDBSD treatment significantly lowered Cytc and caspase-3 expressions and increased Bcl-2 expression in the testicular tissue of TX mice(P<0.05),while U0126 treatment significantly lowered testicular Bcl-2 expression level.No significant differences were found in total protein expression levels of ERK1/2 among the 5 groups,but p-ERK protein expression was significantly reduced in WD and U0126 groups and increased in penicillamine and GDBSD groups.Conclusion GDBSD can improve spermatogenesis and enhance fertility of male TX mice with WD possibly by activating the ERK signaling pathway to enhance proliferation and reduce apoptosis of the spermatogenic cells.关键词
Wilson病/肝豆补肾汤/铜沉积/ERK信号通路/精子发生Key words
Wilson disease/Gandou Bushen Decoction/copper deposition/ERK signaling pathway/spermatogenesis引用本文复制引用
银苗朱,陈奎玉,吴丽敏,江鹏宇,籍志慧,张念,周欢,韩辉..肝豆补肾汤通过激活ERK信号通路减少Wilson病TX小鼠异常精子生成并促进生精细胞增殖[J].南方医科大学学报,2024,44(11):2063-2073,11.基金项目
国家自然科学基金(82374212,81971446,81673811) （82374212,81971446,81673811）
安徽省科技厅临床专项转化项目(202204295107020044) （202204295107020044）
安徽省教育厅重点项目(2022AH050523) Supported by National Natural Science Foundation of China(82374212,81971446,81673811). （2022AH050523）
