Abstract：
BACKGROUND: Apoptosis is an important pathologic mechanism of erectile dysfunction after radical prostatectomy. Studies have shown that programmed cell death factor 4 is connected to the modulation of apoptosis in many cells. However, the programmed cell death factor 4 function in the cavernous nerve injury erectile dysfunction is unclear.
OBJECTIVE: This investigation aimed to explore the programmed cell death factor 4 function in erectile dysfunction in rats with bilateral cavernous nerve crush.
METHODS: The experiment used 30 male Sprague Dawley rats (18 months old) that were screened for normal erectile function by the apomorphine test. Ten rats were randomized into Sham and bilateral cavernous nerve crush groups to detect changes in programmed cell death factor 4 expression. The remaining 20 rats were distributed at random to four groups: the Sham group treated by sham surgery, the phosphate-buffered saline group, the lentivirus containing negative control short hairpin RNA group, and the lentivirus containing short hairpin RNA targeting programmed cell death factor 4 group underwent bilateral cavernous nerve crush and were afterward administered intracavernous injections of phosphate-buffered saline, lentivirus containing negative control short hairpin RNA, or lentivirus containing short hairpin RNA targeting programmed cell death factor 4. Electrical stimulation of the cavernous nerve was conducted 2 weeks later for penile erectile function assessment. The cavernous tissue was collected for histological analysis and western blotting.
RESULTS: The apoptosis level in rat corpus cavernosum was elevated, and programmed cell death factor 4 expression was increased after bilateral cavernous nerve crush. Knockdown of programmed cell death factor 4 significantly improved erectile function in bilateral cavernous nerve crush rats. Furthermore, lentivirus containing short hairpin RNA targeting programmed cell death factor 4 treatment raised smooth muscle content and attenuated cavernous fibrosis and apoptotic levels. Additionally, programmed cell death factor 4 was found to mediate the PI3K/AKT pathway.
CONCLUSIONS: Elevated programmed cell death factor 4 expression may be an important pathogenetic mechanism for erectile dysfunction after bilateral cavernous nerve crush, and the knockdown of programmed cell death factor 4 enhanced erectile function in 18-month-old rats after cavernous nerve damage. The potential mechanism may be the stimulation of the PI3K/AKT pathway to attenuate the cavernous apoptosis level.
OBJECTIVE: This investigation aimed to explore the programmed cell death factor 4 function in erectile dysfunction in rats with bilateral cavernous nerve crush.
METHODS: The experiment used 30 male Sprague Dawley rats (18 months old) that were screened for normal erectile function by the apomorphine test. Ten rats were randomized into Sham and bilateral cavernous nerve crush groups to detect changes in programmed cell death factor 4 expression. The remaining 20 rats were distributed at random to four groups: the Sham group treated by sham surgery, the phosphate-buffered saline group, the lentivirus containing negative control short hairpin RNA group, and the lentivirus containing short hairpin RNA targeting programmed cell death factor 4 group underwent bilateral cavernous nerve crush and were afterward administered intracavernous injections of phosphate-buffered saline, lentivirus containing negative control short hairpin RNA, or lentivirus containing short hairpin RNA targeting programmed cell death factor 4. Electrical stimulation of the cavernous nerve was conducted 2 weeks later for penile erectile function assessment. The cavernous tissue was collected for histological analysis and western blotting.
RESULTS: The apoptosis level in rat corpus cavernosum was elevated, and programmed cell death factor 4 expression was increased after bilateral cavernous nerve crush. Knockdown of programmed cell death factor 4 significantly improved erectile function in bilateral cavernous nerve crush rats. Furthermore, lentivirus containing short hairpin RNA targeting programmed cell death factor 4 treatment raised smooth muscle content and attenuated cavernous fibrosis and apoptotic levels. Additionally, programmed cell death factor 4 was found to mediate the PI3K/AKT pathway.
CONCLUSIONS: Elevated programmed cell death factor 4 expression may be an important pathogenetic mechanism for erectile dysfunction after bilateral cavernous nerve crush, and the knockdown of programmed cell death factor 4 enhanced erectile function in 18-month-old rats after cavernous nerve damage. The potential mechanism may be the stimulation of the PI3K/AKT pathway to attenuate the cavernous apoptosis level.
摘要：
背景：细胞凋亡是前列腺癌根治术后勃起功能障碍的重要病理机制。研究表明，程序性细胞死亡因子4与许多细胞凋亡的调节有关。然而,程序性细胞死亡因子4在海绵状神经损伤勃起功能障碍中的作用尚不清楚。
目的：本研究旨在探讨程序性细胞死亡因子4在双侧海绵体神经挤压大鼠勃起功能障碍中的作用。
方法:实验使用30只雄性SpragueDawley大鼠(18月龄),通过阿朴吗啡试验筛选正常勃起功能。将10只大鼠随机分为假手术组和双侧海绵体神经挤压组，以检测程序性细胞死亡因子4表达的变化。其余20只大鼠随机分为4组:假手术组,磷酸盐缓冲盐水组，慢病毒含有阴性对照短发夹RNA组，含有短发夹RNA靶向程序性细胞死亡因子4的慢病毒组进行双侧海绵体神经挤压，然后进行海绵体内注射磷酸盐缓冲盐水，含有阴性对照短发夹RNA的慢病毒，或含有短发夹RNA靶向程序性细胞死亡因子4的慢病毒。2周后对海绵状神经进行电刺激以评估阴茎勃起功能。收集海绵状组织用于组织学分析和蛋白质印迹。
结果：大鼠海绵体细胞凋亡水平升高，双侧海绵体神经挤压后，程序性细胞死亡因子4表达增加。程序性细胞死亡因子4敲除可明显改善双侧海绵状神经挤压大鼠的勃起功能。此外，含有靶向程序性细胞死亡因子4的短发夹RNA的慢病毒治疗可提高平滑肌含量并减轻海绵状纤维化和凋亡水平。此外,发现程序性细胞死亡因子4介导PI3K/AKT途径。
结论：程序性细胞死亡因子4表达升高可能是双侧海绵体神经挤压后勃起功能障碍的重要发病机制。程序性细胞死亡因子4的敲除增强了海绵状神经损伤后18月龄大鼠的勃起功能。潜在的机制可能是刺激PI3K/AKT途径以减弱海绵状细胞凋亡水平。
目的：本研究旨在探讨程序性细胞死亡因子4在双侧海绵体神经挤压大鼠勃起功能障碍中的作用。
方法:实验使用30只雄性SpragueDawley大鼠(18月龄),通过阿朴吗啡试验筛选正常勃起功能。将10只大鼠随机分为假手术组和双侧海绵体神经挤压组，以检测程序性细胞死亡因子4表达的变化。其余20只大鼠随机分为4组:假手术组,磷酸盐缓冲盐水组，慢病毒含有阴性对照短发夹RNA组，含有短发夹RNA靶向程序性细胞死亡因子4的慢病毒组进行双侧海绵体神经挤压，然后进行海绵体内注射磷酸盐缓冲盐水，含有阴性对照短发夹RNA的慢病毒，或含有短发夹RNA靶向程序性细胞死亡因子4的慢病毒。2周后对海绵状神经进行电刺激以评估阴茎勃起功能。收集海绵状组织用于组织学分析和蛋白质印迹。
结果：大鼠海绵体细胞凋亡水平升高，双侧海绵体神经挤压后，程序性细胞死亡因子4表达增加。程序性细胞死亡因子4敲除可明显改善双侧海绵状神经挤压大鼠的勃起功能。此外，含有靶向程序性细胞死亡因子4的短发夹RNA的慢病毒治疗可提高平滑肌含量并减轻海绵状纤维化和凋亡水平。此外,发现程序性细胞死亡因子4介导PI3K/AKT途径。
结论：程序性细胞死亡因子4表达升高可能是双侧海绵体神经挤压后勃起功能障碍的重要发病机制。程序性细胞死亡因子4的敲除增强了海绵状神经损伤后18月龄大鼠的勃起功能。潜在的机制可能是刺激PI3K/AKT途径以减弱海绵状细胞凋亡水平。
