摘要
目的探讨NOD样受体热蛋白结构域相关蛋白3/含半胱氨酸的天冬氨酸蛋白水解酶1(NLRP3/Caspase-1)焦亡信号通路在高脂饮食诱导的勃起功能障碍(ED)大鼠模型睾丸组织中的表达及西地那非的干预的作用。方法55只SD大鼠随机抽取10只为对照大鼠(对照组),45只采用高脂饲料喂养,筛选出32只ED大鼠,随机分为ED组、Sil(西地那非)组、白介素-18(IL-18)组和IL-18+Sil组。连续给药14d,HE染色观察睾丸组织形态学变化,免疫组化法检测睾丸组织IL-18和内皮型一氧化氮合酶(eNOS)含量及分布,实时荧光定量聚合酶链反应(RT-qPCR)及Western blotting检测大鼠睾丸组织中IL-18、NLRP3、Caspase-1、具有细胞膜打孔活性的gasdermin D蛋白(GSDMD)和eNOS的表达。结果与对照组比较,ED组和IL-18组睾丸组织形态发生明显变化,睾丸组织中IL-18、NLRP3、Caspase-1、GSDMD的mRNA和蛋白表达增高,eNOS的mRNA和蛋白表达降低(P<0.05);与ED组和IL-18组比较,Sil组和IL-18+Sil组IL-18、NLRP3、Caspase-1、GSDMD的mRNA和蛋白表达降低,eNOS的mRNA和蛋白表达增高(P<0.05)。结论西地那非能够通过抑制NLRP3/Caspase-1信号通路减少IL-18诱导的ED大鼠睾丸组织中出现的焦亡。
Objective To investigate the expression of NOD-like receptor thermoprotein structural domain-related protein 3/cysteinyl aspartate specific proteinase-1(NLRP3/Caspase-1)scorch signaling pathway in testicular tissues of a high-fat diet-induced erectile dysfunction rat model and the role of sildenafil intervention.Methods 10 of 55 SD rats were randomly selected as control group,45 rats were fed with high-fat diet to induce ED model.32 ED rats were screened and randomly divided into ED group,Sil(sildenafil)group,interleukin-18(IL-18)group and IL-18+Sil group.After 14 days of continuous administration,HE stain was used to observe the morphological changes,immunohistochemistry was performed to detect the content and distribution of IL-18 and endothelial nitric oxide synthase(eNOS)in testes,real-time fluorescence quantitative polymerase chain reaction(RT-qPCR)and Western blotting were performed to detect the IL-18,NLRP3,Caspase-1,gasdermin D(GSDMD)and eNOS in testes of each group.Results Compared with the normal group,the morphology of testis tissues in the ED group and IL-18 group changed significantly,and the mRNA and protein expression of IL-18,NLRP3,Caspase-1 and GSDMD in testis tissues increased,while the mRNA and protein expression of eNOS decreased(P<0.05).Compared with the ED group and IL-18 group,the mRNA and protein expression of IL-18,NLRP3,Caspase-1 and GSDMD were decreased and the mRNA and protein expression of eNOS were increased in the Sil group and IL-18+Sil group(P<0.05).Conclusions Sildenafil was able to attenuate IL-18-induced scorch death in testicular tissue of ED rats by inhibiting NLRP3/Caspase-1 signaling pathway.
作者
牛阳九
张汐佳
朱兵兵
刘凤霞
NIU Yangjiu;ZHANG Xijia;ZHU Bingbing;LIU Fengxia(Department of Human Anatomy,Basic Medical College,Xinjiang Medical University,Urumqi 830011,Xinjiang,China;Xinjiang Key Laboratory of Molecular Biology for Endemic Diseases,Urumqi 830011,Xinjiang,China)
出处
《中国性科学》
2023年第4期1-6,共6页
Chinese Journal of Human Sexuality
基金
国家自然科学基金(81860781)。
