中国药理学通报2024，Vol.40Issue(9)：1634-1641,8.DOI:10.12360/CPB202404055
D-半乳糖对小鼠睾丸TM4支持细胞连接功能损伤及淫羊藿素的改善作用研究
The protective effect of icaritin on D-galactose-induced TM4 cell junctional function damage
摘要
Abstract
Aim To investigate the mechanism of icar-itin(ICT)on D-galactose(D-gal)-induced TM4 ser-toli cell junctional function damage in vitro.Methods TM4 cells were divided into the normal control group and D-gal treatment group with different concentra-tions.The expression changes of TM 4 cell junction function-related proteins(ZO-1,Occludin,β-catenin and Cx43)and ERα/FAK signaling pathway-related proteins(ERα,FAK and pY397-FAK)were detected by Western blot.The concentration of ICT was screened by MTT method.TM4 cells were divided into normal control group,D-gal treatment group,and D-gal treatment+different concentrations of ICT group.The expression levels of the above proteins were detected by Western blot.Molecular docking was used to study the interaction between ERα and ICT,meanwhile predict the affinity between them.Finally,TM4 cells were di-vided into normal control group,D-gal treatment group,ERα inhibitor group,D-gal+ICT group,and ERα inhibitor+ICT group.The expression levels of the above proteins were detected by Western blot.Re-sults Compared with the normal control group,the ex-pression of junctional function-related proteins(ZO-1,Occludin,β-catenin and Cx43)and ERα/FAK signa-ling pathway-related proteins(ERα,FAK and pY397-FAK)were significantly down-regulated.After treat-ment with ICT,the expression of above proteins were significantly up-regulated.The docking results of ERα and ICT molecules revealed the formation of two hydro-gen bonds between Asp351 amino acid residue of ERα and ICT,with bond distances measuring 3.4Å and 2.4Å.Additionally,the docking binding energy be-tween them was found to be lower than-7 kcal·mol-1.After TM4 cells were treated with ERα inhibi-tor,the expression of above proteins and ERα/FAK signaling pathway-related proteins were significantly down-regulated,while the expression levels of the a-bove proteins did not change significantly after being given ICT protected group.Conclusions D-gal can cause damage to the junctional function of TM4 cells,and ICT can improve this damage,which may be related to the up-regulation of ERα/FAK signaling pathway.关键词
D-半乳糖/TM4细胞/淫羊藿素/雌激素受体α/黏着斑激酶/连接功能Key words
D-galactose/TM4 cells/icaritin/estrogen receptor α/facal adhesion kinase/junctional function引用本文复制引用
姚志丽,赵海霞,马小玉,付国庆,吴杰,宋来新,张长城..D-半乳糖对小鼠睾丸TM4支持细胞连接功能损伤及淫羊藿素的改善作用研究[J].中国药理学通报,2024,40(9):1634-1641,8.基金项目
国家自然科学基金资助项目(No 82074205,82274191) （No 82074205,82274191）
武汉市医学科研项目(No WZ20Q03) （No WZ20Q03）
