JNK、LIMK2抑制剂通过调节c-Jun/Bcl-2/Bax、LIMK2/Cofilin改善阴茎海绵体神经损伤大鼠勃起功能的研究  

JNK and LIMK2 inhibitors can improve the erectile function of rats with cavernous nerve injury by regulating c⁃Jun/Bcl⁃2/Bax and LIMK2/Cofilin

作　　者：李梅[1] 沈景丽 胡苗苗 Li Mei;Shen JingLi;Hu Miaomiao(Department of Radiology,The First People’s Hospital of Huzhou,Huzhou 313000,Zhejiang,China)

机构地区：[1]湖州市第一人民医院放射科,浙江湖州313000

出　　处：《中国男科学杂志》2023年第3期64-70,共7页Chinese Journal of Andrology

摘　　要：目的探究JNK、LIMK2抑制剂对海绵体神经损伤大鼠勃起功能的影响及其作用机制。方法选取72只成年健康雄性Wistar大鼠为研究样本,均建立阴茎海绵体神经损伤模型,随机分为4组(对照组、JNK组、LIMK2组、联合组),每组18只,分别给予安慰剂、JNK抑制剂、LIMK2抑制剂及JNK抑制剂+LIMK2抑制剂,观察各组大鼠勃起功能、LOX-1、NOX、NO、ET-1表达、p-c-Jun阳性凋亡细胞量、p-LIMK2阳性成纤维细胞量,以及Bax、Bcl-2、Caspase-3、eNOS、c-Jun、Cofilin蛋白相对表达。结果JNK、LIMK2、联合组最大ICP/MAP、AUC/MAP显著高于对照组,联合组显著高于JNK、LIMK2组(P<0.05);JNK、LIMK2、联合组NO水平显著高于对照组,联合组显著高于JNK、LIMK2组(P<0.05);JNK、LIMK2、联合组LOX-1、NOX、ET-1水平显著低于对照组,联合组显著低于JNK、LIMK2组(P<0.05);JNK、LIMK2、联合组p-c-Jun阳性凋亡细胞量、p-LIMK2阳性成纤维细胞量显著低于对照组,联合组显著低于JNK、LIMK2组(P<0.05);JNK、LIMK2、联合组Bcl-2、eNOS蛋白相对表达量显著高于对照组,联合组显著高于JNK、LIMK2组(P<0.05);JNK、LIMK2、联合组Bax、Caspase-3蛋白相对表达量显著低于对照组,联合组显著低于JNK、LIMK2组(P<0.05);JNK、LIMK2组、联合组c-Jun、Cofilin蛋白相对表达量显著低于对照组,联合组显著低于JNK、LIMK2组(P<0.05)。结论联合抑制JNK和LIMK2可以通过调节海绵体神经损伤大鼠c-Jun/Bcl-2/Bax和LIMK2/Cofilin通路抑制其海绵体细胞凋亡和纤维化来改善勃起功能。目前,鉴于RP后阴茎康复的局限性,JNK和LIMK2的特异性抑制或可作为海绵体神经损伤诱导的勃起功能障碍患者的特异性治疗靶点之一。Objective To explore the effects of JNK and LIMK2 inhibitors on the erectile function of rats with cavernous nerve injury and mechanism of action.Methods The study sample selected 72 adult healthy male wistar rats,all of which established cavernous nerve injury models,and were randomly divided into 4 groups(control group,JNK group,LIMK2 group,combined group),each with 18 rats,respectively,given placebo,JNK inhibitor,LIMK2 inhibitor and JNK inhibitor+LIMK2 inhibitor,observe the erectile function,LOX⁃1,NOX,NO,ET⁃1 expression,p⁃c⁃Jun positive apoptotic cell quantity,p⁃LIMK2 positive in each group of rats;The amount of fibroblasts and the relative expression of Bax,Bcl⁃2,Caspase⁃3,eNOS,c⁃Jun,Cofilin,and protein.Results The maximum ICP/MAP and AUC/MAP of the JNK,LIMK2,and the combination group were significantly higher than those of the control group,and the combination group was significantly higher than the JNK and LIMK2 group(P<0.05);The NO levels in the JNK,LIMK2,and the combination group significantly higher than the control group,the combined group was significantly higher than the JNK and LIMK2 group(P<0.05);the levels of LOX⁃1,NOX,ET⁃1 in the JNK,LIMK2 and combined group were significantly lower than those of the control group,and the combined group was significantly lower than JNK and LIMK2 group(P<0.05);JNK,LIMK2,and combined group’s p⁃c⁃Jun positive apoptotic cells,p⁃LIMK2 positive fibroblasts were significantly lower than the control group,the combination group was significantly lower than the JNK and LIMK2 group(P<0.05);JNK LIMK2 and combined group’s Bcl⁃2,eNOS protein relative expression was significantly higher than the control group,the combined group was significantly higher than the JNK and LIMK2 group(P<0.05);The relative expression of Bax and Caspase⁃3 protein in the JNK LIMK2 and the combination group was significantly lower than that of the control group,the combination group was significantly lower than the JNK and LIMK2 group(P<0.05);The JNK,LIMK2 and the combi

关 键 词：MAP激酶信号系统 阴茎 神经损伤 勃起功能障碍 大鼠 

分 类 号：R697.1[医药卫生—泌尿科学]