Hypoxia-Induced Phenotypic Transformation of Corpus Cavernosum Smooth Muscle Cells After Cavernous Nerve Crush Injury by Down-Regulating P38 Mitogen-Activated Protein Kinase Expression
Hypoxia-Induced Phenotypic Transformation of Corpus Cavernosum Smooth Muscle Cells After Cavernous Nerve Crush Injury by Down-Regulating P38 Mitogen-Activated Protein Kinase Expression
复制标题
海绵体神经挤压损伤后缺氧诱导的海绵体平滑肌细胞表型转化通过下调 P38 丝裂原激活蛋白激酶表达
DOI：
10.1016/j.esxm.2019.08.005
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发表时间：
2019-12-01
期刊：
影响因子：
2.6
通讯作者：
Lv, Bodong
中科院分区：
文献类型：
--
作者：
Chen, Sixiang;Huang, Xiaojun;Lv, Bodong
简介：海绵体神经（CN）损伤是根治性阴茎海绵体切除术中常见的损伤，它可能直接导致勃起功能障碍（艾德）。目前，有丝分裂原活化蛋白激酶（MAPK）家族蛋白在CN损伤后海绵体平滑肌细胞（CCSMC）表型转化中的作用知之甚少。目的：探讨p38 MAPK在CN损伤后缺氧诱导的CCSMC表型转化中的作用。方法：将20只8周龄雄性SD大鼠随机分为假手术组和CNCI组。在假手术组中，通过识别2种氯化萘对大鼠进行假手术，而不对氯化萘造成直接损害。在CNCI组中，大鼠遭受双侧CN挤压损伤。CCSMCs分离自正常的Sprague-Dawley大鼠阴茎海绵体组织，然后在21%或1%O-2浓度的背景下培养48h.Main Outcome Measures：海绵体内压/平均动脉压进行分析，以测量勃起反应。结果：与假手术组相比，CNCI组大鼠阴茎海绵体内压/平均动脉压比值和α-平滑肌肌动蛋白（α-smooth muscle actin，α-smooth muscle actin，α-smooth muscle actin，α-smooth muscle actin，α-smooth muscle actin）表达明显降低（P = 0.0001; P = 0.016），但波形蛋白表达显著增加（P = 0.023）。CNCI组磷酸化p38水平显著降低（P = 0.017;假手术组：0.17 +/- 0.005; CNCI组：0.14 +/- 0.02）。常氧组CCSMCs呈长梭形，缺氧组CCSMCs呈肥大。缺氧48 h后，α-平滑肌肌动蛋白和磷酸化p38 MAPK的表达明显降低（P = 0.01; P = 0.024，常氧：0.66 +/- 0.18，缺氧：0.26 +/- 0.08），缺氧组缺氧诱导因子-1 α和I型胶原表达显著增加结论：缺氧诱导CNCI后CCSMCs表型转化可能与p38 MAPK磷酸化水平下调有关。版权所有（C）2019，作者。爱思唯尔公司出版代表国际性医学协会
Introduction: Cavernosal nerve (CN) injury is commonly caused by radical prostatectomy surgery, and it might directly lead to erectile dysfunction (ED). Currently, the role of mitogen-activated protein kinase (MAPK) family proteins in phenotypic transformation of corpus cavernosum smooth muscle cell (CCSMC) after CNs injury is poorly understood.Aim: To investigate the role of p38 MAPK in hypoxia-induced phenotypic transformation of CCSMCs after CN injury.Methods: In total, 20 Sprague-Dawley rats (male and 8 weeks of age) were randomly divided into 2 groups, including a sham group and CNCI group. In the sham group, rats were sham-operated by identifying 2 CNs without causing direct damage to the CNs. In the CNCI group, rats were subjected to bilateral CN crush injury. CCSMCs were isolated from the normal corpus cavernosum tissues of the Sprague-Dawley rat and then cultured in 21% or 1% O-2 concentration context for 48 hours.Main Outcome Measures: Intracavernous pressure/mean arterial pressure were analyzed to measure erectile response. The impact of hypoxia on penile pathology, as well as the expression of extracellular signal-regulated kinases, the c-Jun NH2-terminal kinase, and p38 MAPK, were analyzed.Results: Compared with the sham group, the intracavernous pressure/mean arterial pressure rate and alpha-smooth muscle actin expression of CNCI group were decreased significantly (P = .0001; P = .016, respectively), but vimentin expression was significantly increased (P = .023). Phosphorylated p38 level in CNCI group was decreased significantly (P = .017; sham: 0.17 +/- 0.005; CNCI: 0.14 +/- 0.02). The CCSMCs in the normoxia group were long fusiform, whereas the morphology of CCSMCs in the hypoxia group became hypertrophic. After hypoxia for 48 hours, the expression of alpha-smooth muscle actin and phosphorylated p38 MAPK was decreased significantly (P = .01; P = .024, normoxia: 0.66 +/- 0.18, hypoxia: 0.26 +/- 0.08, respectively), and the expression of hypoxia-inducible factor-1 alpha and collagen I was increased significantly in hypoxia group (P = .04; P = .012, respectively).Conclusions: Hypoxia induced the phenotypic transformation of CCSMCs after CNCI might be associated with the downregulation of phosphorylated p38 MAPK. Copyright (C) 2019, The Authors. Published by Elsevier Inc. on behalf of the International Society for Sexual Medicine.