Investigate the effect of Shenling Baizhu Powder on the spermatogenic function of the testes in hyperuricemic mice based on ferroptosis
Objective We aimed to investigate the effect of ferroptosis on Shenling Baizhu Powder,a compound prescription of Chinese herbal medicine,in improving testicular spermatogenic function in hyperuricemic mice with spermatogenic dysfunction. Methods Sixty BALB/c mice were randomly divided into normal group,model group,Shenling Baizhu Powder high-,medium-,and low-dose groups (20.14,10.07,5.04 g/kg,by gavage),and ferrostatin-1(Fer-1) group (0.8 mg/kg,by tail vein injection),with 10 mice each group. Except for the normal group,the other groups were intraperitoneally injected with potassium oxonate suspension[600mg/(kg·d)]for 7 days to establish the hyperuricemic model,and then the corresponding intervention was given for consecutive 14 days. Content of serum uric acid (UA),testicular Fe2+,reduced glutathione (GSH),malondialdehyde (MDA) and superoxide dismutase (SOD) activity were detected by biochemical method. Epididymal and testicular indices were measured. The spermatogenic function of testes was evaluated by eosin-hematoxylin staining. Sperm quality was detected by an automatic animal sperm analyzer. Prussian blue staining was used to detect iron deposition in testicular tissue. Immunohistochemistry was used to detect the related protein expressions of acyl-coenzyme A synthetase long-chain family member 4 (ACSL4) and glutathione peroxidase 4 (GPX4) in testicular tissue. Western blotting was used to detect the related protein expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1(HO-1)/GPX4 signaling pathway in testicular tissue. Results Compared with the normal group,the contents of serum UA,MDA,and Fe2+in the testis tissue of the model group were increased,the GSH content and SOD activity were decreased,the epididymal and testicular index,testicular spermatogenic function,sperm density and activity rate were decreased,and the iron deposition and ACSL4 protein expression in the testis tissue were increased. The expressions of kelch-like ECH-associated protein-1 (Keap1) and Nrf2 were increased. The expressions of nuclear Nrf2,HO-1,GPX4,and recombinant solute carrier family 7 member 11 (SLC7A11) protein were decreased (P<0.01). Compared with the model group,the above indexes in the Shenling Baizhu Powder groups and the Fer-1 group were improved to varying degrees (P<0.05,P<0.01). Conclusion Shenling Baizhu Powder can inhibit the ferroptosis of testicular cells through the Nrf2/HO-1/GPX4 signaling pathway,and improve the testicular spermatogenic function of mice with hyperuricemia spermatogenic dysfunction.
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