Azeez Tooyib A, Rhein Paige R, Pierre Clifford J, Ihrig Colin M, La Favor Justin D
Department of Health, Nutrition, and Food Sciences, Florida State University, Tallahassee, Florida, USA.
FASEB J. 2025 Aug 15;39(15):e70899. doi: 10.1096/fj.202501551R.
Obesity is a major risk factor for erectile dysfunction, whereby excess reactive oxygen species (ROS) in the corpus cavernosum have been implicated as a causative factor. Hydrogen sulfide (HS) is an endogenous gasotransmitter with vasodilatory and antioxidant properties. The objectives of this study were to determine the influence of HS on erectile function, penile ROS, and expressions of endogenous antioxidant genes and proteins in the corpus cavernosum. These objectives were tested by (1) comparing wild type mice to mice deficient in cystathionine γ-lyase (CSE), a major endogenous source of HS; and (2) by feeding wild type mice a control diet or high-fat, high-sucrose Western style diet (WD) for 18 weeks, with subgroups treated with and without the HS prodrug SG1002 for the final 6 weeks of the dietary intervention. Erectile function was assessed by cavernous nerve-stimulated intracavernous pressure measurement, penile interstitial ROS was measured with a microdialysis approach, and cavernous gene and protein expression assessed by qRT-PCR and western blot, respectively. Erectile function was impaired in CSE mice and following the WD, which was significantly improved in WD mice treated with SG1002. Penile ROS levels were increased in CSE mice and following the WD, which were suppressed in WD mice treated with SG1002. The following genes were commonly decreased in CSE mice and increased by SG1002 treatment: Nqo1, Gclc, Gstm1, Gpx1, Gpx4, Hmox1, Txnrd1, and Prdx3. Txnip was reciprocally increased in CSE mice and decreased by SG1002 treatment. These data suggest that HS positively influences erectile function and penile free radical balance, likely through augmentation of the glutathione and thioredoxin endogenous antioxidant systems.
肥胖是勃起功能障碍的主要风险因素，海绵体内过量的活性氧（ROS）被认为是一个致病因素。硫化氢（HS）是一种具有血管舒张和抗氧化特性的内源性气体信号分子。本研究的目的是确定HS对勃起功能、阴茎ROS以及海绵体内内源性抗氧化基因和蛋白质表达的影响。通过以下方式检验这些目的：（1）将野生型小鼠与缺乏胱硫醚γ-裂解酶（CSE，HS的主要内源性来源）的小鼠进行比较；（2）给野生型小鼠喂食对照饮食或高脂、高糖西式饮食（WD）18周，在饮食干预的最后6周，将亚组小鼠分为接受和不接受HS前体药物SG1002治疗两组。通过海绵体神经刺激海绵体内压测量评估勃起功能，用微透析方法测量阴茎间质ROS，分别通过qRT-PCR和蛋白质印迹法评估海绵体基因和蛋白质表达。CSE小鼠和接受WD后勃起功能受损，而接受SG1002治疗的WD小鼠勃起功能显著改善。CSE小鼠和接受WD后阴茎ROS水平升高，而接受SG1002治疗的WD小鼠中ROS水平受到抑制。CSE小鼠中以下基因通常减少，而SG1002治疗使其增加：Nqo1、Gclc、Gstm1、Gpx1、Gpx4、Hmox1、Txnrd1和Prdx3。硫氧还蛋白相互作用蛋白（Txnip）在CSE小鼠中升高，而SG1002治疗使其降低。这些数据表明，HS可能通过增强谷胱甘肽和硫氧还蛋白内源性抗氧化系统，对勃起功能和阴茎自由基平衡产生积极影响。
