GPR120激动剂通过β-Arrestin2途径改善高糖诱导的海绵体内皮细胞功能障碍  

Agonists of G protein-coupled receptor 120 ameliorates high glucose-induced corpus cavernous endothelial cells dysfunction via β-Arrestin2 pathway

作　　者：郑仲杰 程建星 唐文豪[1,2,3] 洪锴[1,2,3] 姜辉 林浩成[1,2,3] ZHENG Zhongjie;CHENG Jianxing;TANG Wenhao;HONG Kai;JIANG Hui;LIN Haocheng(Department of Urology,Peking University Third Hospital,Beijing 100191,China;Reproductive Medicine Center,Peking University Third Hospital,Beijing 100191,China;Department of Andrology,Peking University Third Hospital,Beijing 100191,China;Department of Urology,Peking University First Hospital,Beijing 100034,China;Institute of Urology,Peking University,Beijing 100034,China;Department of Andrology,Peking University First Hospital,Beijing 100034,China)

机构地区：[1]北京大学第三医院泌尿外科,北京100191 [2]北京大学第三医院生殖医学中心,北京100191 [3]北京大学第三医院男科,北京100191 [4]北京大学第一医院泌尿外科,北京100034 [5]北京大学泌尿外科研究所,北京100034 [6]北京大学第一医院男科,北京100034

出　　处：《中国性科学》2024年第3期5-10,共6页Chinese Journal of Human Sexuality

基　　金：国家自然科学基金青年项目(81601272);北京市自然科学基金项目(7212134)。

摘　　要：目的探讨激活G蛋白偶联受体(GPR)120对高糖诱导的人类阴茎海绵体内皮损伤修复的影响,以期为寻找糖尿病性勃起功能障碍(DMED)新的药物开发靶点提供理论依据。方法收集海绵体植入手术患者术中废弃海绵体组织提取海绵体内皮细胞进行原代培养,用高浓度葡萄糖诱导内皮细胞损伤,再以GPR120激动剂治疗,观察对比不同处理的细胞一氧化氮(NO)释放量、细胞迁移、血管生成等功能。结果成功提取人类海绵体内皮细胞进行原代培养并鉴定;发现GPR120在人类海绵体内皮细胞中稳定表达,且与内皮型一氧化氮合酶(eNOS)存在共定位;与高糖损伤组相比,GPR120激动剂治疗组NO释放量、划痕愈合率和血管生成率均显著增加(P<0.05);沉默β-Arrestin2后GPR120激动剂失去原有的治疗效果。结论高糖培养可诱导海绵体内皮细胞功能障碍,GPR120激动剂能够治疗海绵体内皮功能障碍,沉默β-Arrestin2后GPR120激动剂无法改善内皮功能。Objective To investigate the effect of activating G protein-coupled receptor(GPR)120 on the repair of high glucose-induced endothelial injury in the human corpus cavernous,with a view to providing theoretical basis for finding new drug development targets for diabetes mellitus induced erectile dysfunction(DMED)patients.Methods The discarded cavernous tissue from patients undergoing penile prosthesis implantation surgery were collected for primary culture of corpus cavernous endothelial cells.Endothelial cell injury was induced with high concentrations of glucose,and then treated with GPR120 agonists.The cellular nitric oxide(NO)emissions,cell migration,angiogenesis functions were observed and compared in different treatment.Results Human corpus cavernous endothelial cells were successfully extracted for primary culture and identified.GPR120 was found to be stably expressed in human corpus cavernous endothelial cells with colocalization with endothelial nitric oxide synthase(eNOS).Compared with the high glucose injury group,the GPR120 agonists treated group showed significant increases in NO emissions,scratch healing rate,and angiogenesis rates(P<0.05).After silencing β-arrestin2,GPR120 agonists lost their original therapeutic effects.Conclusions High glucose culture induces corpus cavernous endothelial cells dysfunction,and GPR120 agonists can treat corpus cavernous endothelial cells dysfunction.After silencing of β-arrestin2,GPR120 agonists fail to improve endothelial function.

关 键 词：勃起功能障碍 糖尿病 海绵体内皮细胞 G蛋白偶联受体120 β-Arrestin2 

分 类 号：R698[医药卫生—泌尿科学]