摘要
目的:探讨磷酸二酯酶5(PDE5)抑制剂西地那非对巨噬细胞极化介导的慢性盆腔疼痛痛觉和炎症的机制。方法:32只成年Wistar大鼠随机分为4组:Sham组、实验性自身免疫性前列腺炎(EAP)组、Sildenafil^(+)EAP组、MET^(+)Sildenafil^(+)EAP组,每组8只。皮下注射前列腺抗原(PAg)和弗氏完全佐剂诱导EAP模型,Sham组注射等量生理盐水,西地那非治疗EAP大鼠,另外,Sildenafil^(+)EAP处理基础上注射巨噬细胞M2型极化抑制剂二甲双胍。HE染色分析前列腺组织病理变化;von Frey纤维法检测大鼠盆腔痛觉反应率;ELISA检测血清细胞因子IL-10和TNF-α水平。流式细胞术检测血清iNOS^(+)和CD16/32^(+)巨噬细胞数量及CD206^(+)、CD10^(+)巨噬细胞数量。结果:与Sham组相比,EAP组前列腺腹侧腺体组织出现明显局灶性或多灶性炎症,盆腔痛觉反应率、血清炎症因子TNF-α水平、巨噬细胞M1型极化特征iNOS^(+)和CD16/32^(+)细胞数量显著升高(均P<0.05),而巨噬细胞M2型极化特征IL-10水平和CD206^(+)、CD10^(+)巨噬细胞数量显著减少(均P<0.05)。与EAP组相比,Sildenafil^(+)EAP组盆腔痛觉反应率、TNF-α水平、iNOS^(+)和CD16/32^(+)细胞数量显著降低(均P<0.05),而IL-10水平和CD206^(+)、CD10^(+)巨噬细胞数量显著升高(均P<0.05)。与Sildenafil^(+)EAP组相比,MET^(+)Sildenafil^(+)EAP组盆腔痛觉反应率、TNF-α水平、iNOS^(+)和CD16/32^(+)细胞数量显著升高(均P<0.05),而IL-10水平和CD206^(+)与CD10^(+)巨噬细胞数量显著降低(均P<0.05)。结论:PDE5抑制剂西地那非通过促进M2巨噬细胞极化阻断慢性盆腔疼痛和炎症。
Objective:To investigate mechanism of phosphodiesterase 5(PDE5)inhibitor Sildenafil in treatment of pain and inflammation in chronic pelvic pain mediated by macrophage polarization.Methods:A total of 32 adult Wistar rats were divided into 4 groups:Sham group,Experimental autoimmune prostatitis(EAP)group,Sildenafil^(+)EAP group,MET^(+)Sildenafil^(+)EAP group,with 8 rats in each group.EAP model was induced by subcutaneous injection of prostate antigen(PAg)and complete Fredrin adjuvant,Sham group was injected with equivalent normal saline.EAP rats were treated with Sildenafil.Metformin was injected on basis of Sildenafil^(+)EAP.HE staining was used to analyze pathological changes of prostate.Response rate of pelvic pain in rats was measured by von Frey fiber method.Serum cytokines IL-10 and TNF-αlevels were determined by ELISA.Numbers of iNOS^(+)and CD16/32^(+)macrophages and CD206^(+)and CD10^(+)macrophages in serum were detected by flow cytometry.Results:Compared with Sham group,EAP group showed obvious focal or multifocal inflammation in ventral prostate gland tissues,pelvic pain response rate,serum inflammatory factor TNF-αlevel,and number of M1-type polarization characteristic iNOS^(+)and CD16/32^(+)cells in EAP group were significantly increased(all P<0.05),while M2-type polarization characteristics of macrophages,IL-10 level and number of CD206^(+)and CD10^(+)macrophages were significantly decreased(all P<0.05).Compared with EAP group,pelvic pain response rate,TNF-αlevel,iNOS^(+)and CD16/32^(+)cell number in Sildenafil^(+)EAP group were significantly decreased(all P<0.05),while IL-10 level and CD206^(+)and CD10^(+)macrophage number were significantly increased(all P<0.05).Compared with Sildenafil^(+)EAP group,pelvic pain response rate,TNF-αlevel,iNOS^(+)and CD16/32^(+)cells in MET^(+)Sildenafil^(+)EAP group were significantly increased(all P<0.05),while IL-10 level and number of CD206^(+)and CD10^(+)macrophages were significantly decreased(all P<0.05).Conclusion:Sildenafil,a PDE5 inhibitor,blocks chronic pelvic pain and inflammation by promoting polarization of M2 macrophages.
作者
陈梅珠
罗琳
田毅
CHEN Meizhu;ROWLING;TIAN Yi(Department of Anesthesiology,Affiliated Haikou Hospital,Xiangya School of Medicine,Central South University/Haikou People's Hospital,Haikou 570208,China)
出处
《中国免疫学杂志》
CAS
CSCD
北大核心
2024年第8期1620-1624,1633,共6页
Chinese Journal of Immunology
基金
海南省卫生健康行业科研项目(21A200042)。
