西地那非对勃起功能障碍模型大鼠主动脉血管组织中NLRP3/caspase-1通路的影响  

Effect of sildenafil on NLRP3/caspase-1 pathway in the aorta vascular tissue of rat models with erectile dysfunction

作　　者：张汐佳 朱兵兵 杨承霞 牛立盼 刘凤霞 ZHANG Xijia;ZHU Bingbing;YANG Chengxia;NIU Lipan;LIU Fengxia(Department of Human Anatomy,Basic Medical College,Xinjiang Medical University,Urumqi 836001;Xinjiang Key Laboratory of Molecular Biology of Endemic Diseases,Urumqi 836001,China)

机构地区：[1]新疆医科大学基础医学院人体解剖学教研室,新疆乌鲁木齐836001 [2]新疆地方病分子生物学重点实验室,新疆乌鲁木齐836001

出　　处：《基础医学与临床》2023年第11期1636-1641,共6页Basic and Clinical Medicine

基　　金：国家自然科学基金(81860781)。

摘　　要：目的探讨西地那非(Sil)对勃起功能障碍(ED)大鼠主动脉血管组织中NLRP3/caspase-1通路蛋白表达的影响作用。方法建立ED大鼠模型,随机分为ED组、Sil组,另取10只大鼠作为对照组。Sil组给予20 mg/kg西地那非灌胃(1次/d,连续2周)后,HE染色观察主动脉血管组织形态变化;Masson染色检测主动脉纤维化;免疫组化测定主动脉中白细胞介素-1β(IL-1β)和内皮源性一氧化氮合酶(eNOS)的含量及分布;RT-qPCR及Western blot检测主动脉中NLRP3、caspase-1、GSDMD、IL-1β和eNOS的表达。结果ED组大鼠主动脉血管组织形态发生病理变化,内皮细胞局部脱落较多,纤维化明显;主动脉中NLRP3、caspase-1、GSDMD、IL-1β的mRNA和蛋白表达均增高,eNOS的mRNA和蛋白表达均降低(P<0.05)。与ED组相比,Sil组大鼠主动脉血管组织形态学病理变化改善,内皮局部细胞脱落减少,纤维化减轻;主动脉中NLRP3、caspase-1、GSDMD、IL-1β的mRNA和蛋白表达降低,eNOS的mRNA和蛋白表达增高(P<0.05)。结论Sil促进ED大鼠主动脉血管组织中NLRP3/caspase-1通路蛋白的表达,Sil可能通过抑制此通路改善ED大鼠炎性反应、血管纤维化和内皮功能障碍,进而促进大鼠的勃起功能。Objective To investigate the effect of sildenafil(Sil)on the expression of NLRP3/caspase-1 pathway in the aorta vascular tissue of erectile dysfunction(ED)rat models.Methods ED rat model was established and randomly divided into ED group and Sil group.Another 10 rats were selected as control group.After intragastric administration of Sil(20 mg/kg,once a day for 2 weeks),HE staining was used to observe the morphological change of aorta.Aortic fibrosis was detected by Masson staining.The content and distribution of interleukin-1β(IL-1β)and endothelial nitric oxide synthase(eNOS)in aorta were determined by immunohistochemistry.RT-qPCR and Western blot were used to detect the expression of NLRP3,caspase-1,GSDMD,IL-1βand eNOS in the aorta.Results In ED group,there were pathological changes in aortic morphology,more local exfoliation of endothelial cells and obvious fibrosis.The mRNA and protein expressions of NLRP3,caspase-1,GSDMD and IL-1βwere increased,and the mRNA and protein expressions of eNOS were decreased in the aorta of the rats in the experimental group(P<0.05).Compared with the ED group,the aortic morphological changes of the Sil group were improved,the local endothelial cell shedding was reduced,and the fibrosis was alleviated.The mRNA and protein expression of NLRP3,caspase-1,GSDMD and IL-1βdecreased,while the mRNA and protein expression of eNOS increased in aorta(P<0.05).Conclusions The expression of NLRP3/caspase-1 pathway protems in the aorta vescular tissue of rats with ED is up-regulated by Sil,which may improve the inflammatory response,vascular fibrosis and endothelial dysfunction by inhibiting the NLRP3/caspase-1 pathway in the aorta vascular tissue of rats with ED.

关 键 词：西地那非 勃起功能障碍 主动脉 焦亡 

分 类 号：R322.6[医药卫生—人体解剖和组织胚胎学]