سابِق|تال

Investigate the effect of Shenling Baizhu Powder on the spermatogenic function of the testes in hyperuricemic mice based on ferroptosis

  • role： First author第一作者
  • Affiliation：

    Laboratory Animal Center, Hubei University of Chinese Medicine, Wuhan 430065, China

    Hubei Shizhen Laboratory, Wuhan 430061, China

  • Introduction：江晓翠，女，实验师，在读博士生
JIANG Xiaocui12,  
  • Affiliation：

    Laboratory Animal Center, Hubei University of Chinese Medicine, Wuhan 430065, China

    Hubei Shizhen Laboratory, Wuhan 430061, China

XIAO Min12,  
  • Affiliation：

    Hubei Shizhen Laboratory, Wuhan 430061, China

    College of Basic Medical Sciences, Hubei University of Chinese Medicine, Wuhan 430065, China

LYU Yinjuan23,  
  • Affiliation：

    Hubei Shizhen Laboratory, Wuhan 430061, China

    College of Basic Medical Sciences, Hubei University of Chinese Medicine, Wuhan 430065, China

WANG Chaoyang23,  
  • Affiliation：

    College of Basic Medical Sciences, Hubei University of Chinese Medicine, Wuhan 430065, China

ZHU Zhongyi3,  
  • Affiliation：

    College of Basic Medical Sciences, Hubei University of Chinese Medicine, Wuhan 430065, China

HAO Heng3,  
  • role： Corresponding author通信作者
  • Affiliation：

    Hubei Shizhen Laboratory, Wuhan 430061, China

    College of Basic Medical Sciences, Hubei University of Chinese Medicine, Wuhan 430065, China

  • Email：774941339@qq.com
  • Introduction：Prof. CAO Jigang, Ph.D., Chief Physician, Doctoral Supervisor. Hubei University of Chinese Medicine, No. 16, Huangjiahu West Road, Qingling Street, Hongshan District, Wuhan 430065. E-mail: 774941339@qq.com
CAO Jigang23*

ملخص

ObjectiveWe 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.MethodsSixty 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 [600 mg/(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.ResultsCompared 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).ConclusionShenling 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.

مفهوم

Shenling Baizhu Powder;hyperuricemia;spermatogenesis dysfunction;nuclear factor erythroid 2-related factor 2/heme oxygenase-1/glutathione peroxidase 4 signaling pathway;ferroptosis;mice

References

  1. [1].
    ZHAO Q, HUANG JF, CHENG Y, et al. Polyamine metabolism links gut microbiota and testicular dysfunction[J]. Microbiome, 2021, 9(1): 224.
  2. [2].
    DONG F, PING P, WANG SQ, et al. Identification and validation of CCL2 as a potential biomarker relevant to mast cell infiltration in the testicular immune microenvironment of spermatogenic dysfunction[J]. Cell Biosci，2023，13(1): 94.
  3. [3].
    LEVINE H, JØRGENSEN N, MARTINO-ANDRADE A, et al. Temporal trends in sperm count: a systematic review and meta-regression analysis of samples collected globally in the 20th and 21st centuries[J]. Hum Reprod Update，2023, 29(2): 157-176.
  4. [4].
    EISENBERG ML, ESTEVES SC, LAMB DJ, et al. Male infertility[J]. Nat Rev Dis Primers, 2023, 9: 49.
  5. [5].
    韩瑞钰，马婧，崔彤，等. 高尿酸血症对不育男性精液参数的影响[J]. 中华男科学杂志，2018, 24(12): 1069-1072.
  6. [6].
    江晓翠，田代志，刘祺，等. 参苓白术散调节Nrf2/ARE通路改善高尿酸血症型少弱精子症小鼠的生精功能[J]. 中国实验方剂学杂志，2023, 29(15): 22-30.
  7. [7].
    ADINOLFI S, PATINEN T, JAWAHAR DEEN A, et al. The KEAP1-NRF2 pathway: targets for therapy and role in cancer[J]. Redox Biol, 2023, 63: 102726.
  8. [8].
    YANG SX, WANG LS, ZENG Y, et al. Salidroside alleviates cognitive impairment by inhibiting ferroptosis via activation of the Nrf2/GPX4 axis in SAMP8 mice[J]. Phytomedicine, 2023, 114: 154762.
  9. [9].
    JIN ZR, YANG YZ, CAO YL, et al. The gut metabolite 3-hydroxyphenylacetic acid rejuvenates spermatogenic dysfunction in aged mice through GPX4-mediated ferroptosis[J]. Microbiome, 2023, 11(1): 212.
  10. [10].
    SHEN K, WANG XJ, WANG YW, et al. MiR-125b-5p in adipose derived stem cells exosome alleviates pulmonary microvascular endothelial cells ferroptosis via Keap1/Nrf2/GPX4 in sepsis lung injury[J].Redox Biol, 2023, 62: 102655.
  11. [11].
    江晓翠，田代志，赵敏，等. 高尿酸血症对小鼠生精功能和精子质量的影响及其机制[J]. 天津医药，2023, 51(4): 376-381.
  12. [12].
    魏伟，吴希美，李元建. 药理实验方法学[M]. 4版. 北京：人民卫生出版社，2010: 71-72.
  13. [13].
    李玲，黄家望，冯芷莹，等. 基于铁死亡途径探讨龟鹿二仙胶治疗少弱精子症的作用及机制[J]. 中草药，2023, 54(20): 6722-6733.
  14. [14].
    JEREMY M, GURUSUBRAMANIAN G, KHARWAR RK, et al. Evaluation of a single dose of intra-testicular insulin treatment in heat-stressed mice model[J]. Andrologia, 2022, 54(11): e14603.
  15. [15].
    黄金娟，邓奕辉. 基于升清降浊理论从脾胃论治高尿酸血症[J]. 中医临床研究，2024, 16(5): 120-124.
  16. [16].
    衡琪琪，陈志亮，袁帅，等. 顾宁从湿浊论治无症状高尿酸血症经验[J]. 山西中医，2023, 39(11)：5-7.
  17. [17].
    张世俊，李春雨，韩静. 健脾补肾化痰排浊法治疗高尿酸血症21例[J]. 四川中医，2023, 41(12): 110-112.
  18. [18].
    苏奔，王灿晖，朱晓琳，等. 王灿晖教授辨治无症状高尿酸血症思想撷要[J]. 时珍国医国药，2022, 33(12): 3005-3006.
  19. [19].
    MIAKE J, HISATOME I, TOMITA K, et al. Impact of hyper- and hypo- uricemia on kidney function[J]. Biomedicines, 2023, 11(5): 1258.
  20. [20].
    LIU Y, JIANG ML, ZHAO ZY, et al. Cyclic amplification of intracellular ROS boosts enzymatic prodrug activation for enhanced chemo-immunotherapy[J]. Acta Biomater, 2023, 166: 567-580.
  21. [21].
    焦丹丽，马秉哲，赵琛，等. 铁死亡在睾丸生精功能障碍中的机制研究进展[J].中华男科学杂志，2022, 28(11): 1044-1048.
  22. [22].
    WANG Y, WU J, ZHANG MM, et al. Cadmium exposure during puberty damages testicular development and spermatogenesis via ferroptosis caused by intracellular iron overload and oxidative stress in mice[J]. Environ Pollut, 2023, 325: 121434.
  23. [23].
    LI XJ, WANG WT, HOU Y, et al. Arsenic interferes with spermatogenesis involving Rictor/mTORC2-mediated blood-testis barrier disruption in mice[J]. Ecotoxicol Environ Saf, 2023, 257: 114914.
  24. [24].
    DING J, LU BW, LIU LM, et al. Guilu-Erxian-Glue alleviates Tripterygium wilfordii polyglycoside-induced oligoasthenospermia in rats by resisting ferroptosis via the Keap1/Nrf2/GPX4 signaling pathway[J]. Pharm Biol, 2023, 61(1): 213-227.
  25. [25].
    ABDULLAH F, KHAN NOR-ASHIKIN MN, AGARWAL R, et al. Glutathione (GSH) improves sperm quality and testicular morphology in streptozotocin-induced diabetic mice[J]. Asian J Androl, 2021, 23(3): 281-287.
  26. [26].
    YAN XY, LIU YD, LI CC, et al. Pien-Tze-Huang prevents hepatocellular carcinoma by inducing ferroptosis via inhibiting SLC7A11-GSH-GPX4 axis[J]. Cancer Cell Int, 2023, 23(1): 109.
  27. [27].
    LIU H, ZHANG TA, ZHANG WY, et al. Rhein attenuates cerebral ischemia-reperfusion injury via inhibition of ferroptosis through NRF2/SLC7A11/GPX4 pathway[J]. Exp Neurol, 2023, 369: 114541.
  28. [28].
    DING SY, DUANMU XY, XU LS, et al. Ozone pretreatment alleviates ischemiareperfusion injury-induced myocardial ferroptosis by activating the Nrf2/Slc7a11/Gpx4 axis[J]. Biomed Pharmacother, 2023, 165: 115185.
  29. [29].
    HAN P, WANG X, ZHOU TQ, et al. Inhibition of ferroptosis attenuates oligospermia in male Nrf2 knockout mice[J]. Free Radic Biol Med, 2022, 193(Pt 1): 421-429.

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