Study on role of IL-18-mediated NLRP3/NF-κB signaling pathway in erectile dysfunction rats and drug intervention
10.3969/j.issn.1000-484X.2025.09.013
- VernacularTitle:IL-18介导的NLRP3/NF-κB信号通路在勃起功能障碍大鼠中的作用及药物干预的研究
- Author:
Rui ZHANG
1
;
Chengxia YANG
1
;
Bingbing ZHU
1
;
Lipan NIU
1
;
Yulian LIU
1
;
Fengxia LIU
1
Author Information
1. 新疆医科大学基础医学院人体解剖学教研室,乌鲁木齐 830011;新疆地方病分子生物学重点实验室,乌鲁木齐 830011
- Publication Type:Journal Article
- Keywords:
Erectile dysfunction;
Inflammation;
NLRP3/NF-κB signaling pathway;
Penis;
Sildenafil
- From:
Chinese Journal of Immunology
2025;41(9):2131-2135,2140
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the expression of the proinflammatory factor IL-18-mediated NOD-like receptor thermal protein domain associated protein 3/nuclear factor κB(NLRP3/NF-κB)signaling pathway in penile tissues of rats with high-fat diet-in-duced erectile dysfunction(ED),and to explore the intervention effect of sildenafil.Methods:Fifty-five sexually normal male SD rats were randomly divided into 10 cases as the normal control group,and the rest of the rats were fed with high-fat chow to establish the ED rat model,and the successfully screened ED rats were randomly divided into the ED group,the Sil group,the IL-18 group,and the IL-18+Sil group,with 8 rats in each group.Following 14 days of nonstop treatment,the morphological alterations in the penile tis-sue were observed by HE staining.Using immunohistochemistry,the amount and distribution of NF-κB p65 and Adropin in penile tis-sues were found.RT-qPCR was used to identify the expression of NLRP3 and NF-κB p65 mRNA in penile tissues.Western blot exami-nation showed the expression of the proteins NLRP3,pro-IL-18,p-NF-κB p65,NF-κB p65,and Adropin in penile tissues.Results:The ED group showed altered penis tissue morphology,destroyed muscle fibers,enlarged sinus cavity,increased mRNA and protein expressions of NLRP3,p-NF-κB p65/NF-κB p65,and pro-IL-18(all P<0.05),and decreased Adropin protein expression(P<0.05).While the protein expression of Adropin was increased(P<0.05),the mRNA and protein expressions of NLRP3,p-NF-κB p65/NF-κB p65,and pro-IL-18 in the penis tissues were decreased(all P<0.05)when compared to the ED group.The muscle fibers and sinus cav-ities of the penis were recovered to varying degrees in the Sil group.The IL-18 group experienced the destruction of muscle fibers,an enlargement of the sinus cavity,an increase in the mRNA and protein expressions of NLRP3,p-NF-κB p65/NF-κB p65,and pro-IL-18 in the penile tissues(all P<0.05),as well as a decrease in the protein expression of Adropin(P<0.05).The rat penile tissues in the IL-18+Sil group showed variable degrees of recovery in the muscle fibers and sinus cavities when compared to the IL-18 group.Ad-ditionally,there was a drop(all P<0.05)in the expressions of NLRP3,pro-IL-18 m RNA and protein,p-NF-κB p65/NF-κB p65,and p-NF-κB p65 in the penile tissues.The expression of the Adropin protein was elevated(P<0.05).Conclusion:Significant changes have been observed in the NLRP3/NF-κB signaling pathway,which is regulated by IL-18,in the hyperlipidemia ED rat model.In ED rats,sildenafil can increase erectile function by promoting the production of Adropin and blocking the activation of this pathway.
