中国中西医结合杂志2024，Vol.44Issue(11)：1372-1379,8.DOI:10.7661/j.cjim.20240722.109
淫羊藿苷调控P53/SLC7A11/GPX4通路抑制睾丸细胞铁死亡改善少弱精子症小鼠生精功能
Icariin Improved Spermatogenic Function in Mice with Oligospermia through Inhibiting Testicular Ferroptosis via Regulating P53/SLC7A11/GPX4 Pathway
摘要
Abstract
Objective To investigate the effect and mechanism of icariin in improving oligospermia mice through tumor suppressor factor(P53)/solute carrier family 7 member 11(SLC7A11)/glutathione peroxidase 4(GPX4)pathway.Methods KM mice were randomly divided into blank group,model group,high,medium,low icariin(117.0,58.5,29.3 mg·kg-1)and levocarnitine(400 mg·kg-1)group,with 10 mice in each group.Except for the blank group,adenine(1.25 g·kg-1)was administered intragastrically for 14 days to establish a model of oligoasthenospermia,and the corresponding dose of drug was administered intragastrically for 21 days.Sperm quality was detected by animal sperm analyzer.ELISA was used to detect serum testosterone(T),estradiol(E2)and follicle-stimulating hormone(FSH)levels.HE was used to evaluate testicular spermatogenic function.Prussian blue staining was used to evaluate testicular iron deposition.Immunohistochemistry was used to evaluate testicular tissue SLC7A11 and GPX4 protein expression.Biochemical analysis was used to detect the activity of superoxide dismutase(SOD)and malondialdehyde(MDA)content in testicular tissue.Western Blot and RT-PCR was used to detect the protein and mRNA expression of P53,GPX4,SLC7A11 in testicular tissues,respectively.Results In the model group,the distribution of seminiferous tubules was loose,and the arrangement of spermatogenic cells was disordered,and only a small number of sperm could be seen in the lumen.After the intervention in each intervention group,the morphology of the testes was significantly improved,the spermatogenic cells increased to varying degrees,and more free sperm could be observed in the lumen.Compared with the blank group,the sperm density and motility rate,serum T and E2 levels,total testicular spermatogenic function score(TMS),testicular tissue SLC7A11,GPX4 protein and mRNA expression,and SOD activity decreased(P＜0.01),while serum FSH level,the positive average optical density(AOD)of iron deposition,MDA content in testicular tissue,and P53 protein and mRNA expression increased in the model group(P＜0.01).Compared with the model group,the serum T level,GPX4 protein and mRNA expression,P53 mRNA expression and SOD activity increased,the serum FSH level decreased in the intervention group(P＜0.05,P＜0.01).Except for icariin low-dose group,sperm density and motility,serum E2 level,TMS,testicular tissue SLC7A11 protein and mRNA expression increased(P＜0.05,P＜0.01),the positive AOD of iron deposition,and the expression of P53 protein in testicular tissue decreased in other intervention groups(P＜0.05,P＜0.01).The expression of SLC7A11 protein in testicular tissues of mice increased in the icariin high-dose and medium-dose groups(P＜0.05).While the content of MDA in testicular tissues of mice in the icariin high-dose group and levocamitine group decreased(P＜0.05).Conclusion The mechanism by which icariin improves testicular spermatogenesis in mice with oligospermia may involve regulating the P53/SLC7A11/GPX4 pathway and inhibiting testicular ferroptosis.关键词
淫羊藿苷/少弱精子症/肿瘤抑制因子/溶质载体家族7成员11/谷胱甘肽过氧化物酶4/铁死亡/睾丸生精功能Key words
icariin/oligoasthenospermia/tumor suppressor factor/solute carrier family 7 member 11/glutathione peroxidase 4/ferroptosis/testicular spermatogenesis function引用本文复制引用
江晓翠,萧闵,刘祺,赵敏,吕银娟,陈思易,曹继刚..淫羊藿苷调控P53/SLC7A11/GPX4通路抑制睾丸细胞铁死亡改善少弱精子症小鼠生精功能[J].中国中西医结合杂志,2024,44(11):1372-1379,8.基金项目
国家自然科学基金青年项目(No.82104704) （No.82104704）
湖北省中医药管理局中医药重点项目(No.ZY2023Z024) （No.ZY2023Z024）
湖北省中医药管理局中医药指导性项目(No.ZY2023F134) （No.ZY2023F134）
武汉中青年名中医项目(No.武卫[2019]17号) （No.武卫[2019]17号）
湖北中医药大学校级科研平台项目(No.中医校[2022]80号) （No.中医校[2022]80号）
湖北省教育厅科研计划项目(No.D20222006) （No.D20222006）
