The effects of single versus combined therapy using LIM-kinase 2 inhibitor and type 5 phosphodiesterase inhibitor on erectile function in a rat model of cavernous nerve injury-induced erectile dysfunction  

作　　者：Min Chui Cho Junghoon Lee Juhyun Park Sohee Oh Ji Sun Chai Hwancheol Son Jae-Seung Paick Soo Woong Kim 

机构地区：[1]Department of Urology,Seoul National University College of Medicine,SMG-SNU Boramae Medical Center,Seoul 07061,Korea [2]Department of Urology,Seoul National University College of Medicine,Seoul National University Hospital,Seoul 03080,Korea [3]Department of Biostatistics,Seoul National University College of Medicine,SMG-SNU Boramae Medical Center,Seoul 07061,Korea

出　　处：《Asian Journal of Andrology》2019年第5期493-500,共8页亚洲男性学杂志（英文版）

摘　　要：We aimed to determine whether combination of LIM-kinase 2 inhibitor(LIMK2i)and phosphodiesterase type-5 inhibitor(PDE5i)could restore erectile function through suppressing cavernous fibrosis and improving caver nous apoptosis in a rat model of cavernous nerve crush injury(CNCI).Seventy 12-week-old Sprague-Dawley rats were equally distributed into five groups as follows:(1)sham surgery(Group S),(2)CNCI(Group I),(3)CNCI treated with daily intraperitoneal administration of 10.0 mg kg^-1 LIMK2i(Group I+L),(4)daily oral administration of 20.0 mg kg-1 udenafil,PDE5i(Group I+U),and(5)combined administration of 10.0 mg kg^-1 LIMK2i and 20.0 mg kg^-1 udenafil(Group I+L+U).Rats in Groups I+L,I+U,and I+L+U were treated with respective regimens for 2 weeks after CNCI.At 2 weeks after surgery,erectile response was assessed using electrostimulation.Penile tissues were processed for histological studies and western blot.Group I showed lower intracavernous pressure(ICP)/mean arterial pressure(MAP),lower area under the curve(AUC)/MAP,decreased immunohistochemical staining for alpha-smooth muscle(SM)actin,higher apoptotic index,lower SM/collagen ratio,increased phospho-LIMK2-positive fibroblasts,decreased protein kinase B/endothelial nitric oxide synthase(Akt/eNOS)phosphorylation,increased LIMK2/cofilin phosphorylation,and increased protein expression of fibronectin,compared to Group S.In all three treatment groups,erectile responses,protein expression of fibronectin,and SM/collagen ratio were improved.Group I+L+U showed greater improvement in erectile response than Group I+L.SM content and apoptotic index in Groups I+U and I+L+U were improved compared to those in Group I.However,Group I+L did not show a significant improvement in SM content or apoptotic index.The number of phospho-LIMK2-positive fibroblasts was normalized in Groups I+L and I+L+U,but not in Group I+U.Akt/eNOS phosphorylation was improved in Groups I+U and I+L+U,but not in Group I+L.LIMK2/cofilin phosphorylation was improved in Groups I+L and I+L+U,but not in Group

关 键 词：apoptosis erectile DYSFUNCTION FIBROSIS LIM KINASE PHOSPHODIESTERASE 

分 类 号：R73[医药卫生—肿瘤]