Vacuum therapy ameliorates erectile dysfunction in bilateral cavernous nerve crush rats by inhibiting apoptosis and activating autophagy.

Vacuum therapy ameliorates erectile dysfunction in bilateral cavernous nerve crush rats by inhibiting apoptosis and activating autophagy.
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真空疗法通过抑制细胞凋亡和激活自噬改善双侧海绵神经挤压大鼠的勃起功能障碍

DOI:
10.4103/aja.aja_79_20
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发表时间:
2021-05
影响因子:
2.9
通讯作者:
Yuan JH
Yuan JH
中科院分区:
医学2区
文献类型:
--
作者:
Wu CJ;Fu FD;Qin F;Ma M;Li T;Wei SZ;Yu BT;Yang XZ;Yuan JH

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尽管手术技术有所改进,但阴茎切除术后勃起功能障碍(pPED)仍然是当前的问题。真空治疗在临床上被证实为pPED康复的一种类型。然而,其潜在的机制并不完全了解。最近,自噬和细胞凋亡在糖尿病、衰老和雄激素剥夺引起的勃起功能障碍中被广泛研究,但在pPED和真空治疗的背景下没有研究。因此,本研究旨在研究自噬和凋亡在pPED和真空治疗中的作用。将24只成年雄性SD大鼠随机分为3组:对照组、双侧海绵体神经挤压组(BCNC)和BCNC +负压组。治疗4周后,阴茎海绵体内压用于评估勃起功能。采用实时定量聚合酶链反应、免疫印迹和免疫组化方法检测其分子表达。TdT介导的dUTP缺口末端标记染色用于评估细胞凋亡。透射电镜观察自噬体。与BCNC组比较,治疗后勃起功能和海绵体缺氧改善有统计学意义(P < 0.05)。细胞凋亡及B细胞淋巴瘤2相关X和切割型Caspase 3蛋白的相对表达量降低(P < 0.05)。自噬相关分子,如磷酸化的unc-51样自噬激活激酶1(Ser 757)和p62减少。Beclin 1、微管相关蛋白1轻链3 A/B和自噬体表达增加(P < 0.05)。此外,磷脂酰肌醇3-激酶/AKT/哺乳动物雷帕霉素靶蛋白信号通路作为自噬的负调控因子在一定程度上受到抑制。本研究表明,真空治疗通过抑制细胞凋亡和激活自噬来改善BCNC大鼠的pPED。
Postprostatectomy erectile dysfunction (pPED) remains a current problem despite improvements in surgical techniques. Vacuum therapy is clinically confirmed as a type of pPED rehabilitation. However, its underlying mechanisms are incompletely understood. Recently, autophagy and apoptosis were extensively studied in erectile dysfunction resulting from diabetes, senescence, and androgen deprivation but not in the context of pPED and vacuum therapy. Therefore, this study was designed to investigate the roles of autophagy and apoptosis in pPED and vacuum therapy. Twenty-four adult male Sprague–Dawley rats were randomly divided into three groups: the control group, bilateral cavernous nerve crush (BCNC) group, and BCNC + vacuum group. After 4 weeks of treatment, intracavernosal pressure was used to evaluate erectile function. Real-time quantitative polymerase chain reaction, western blot, and immunohistochemistry were used to measure the molecular expression. TdT-mediated dUTP nick-end labeling staining was used to assess apoptosis. Transmission electron microscopy was used to observe autophagosomes. After treatment, compared with those of the BCNC group, erectile function and cavernosal hypoxia had statistically significantly improved (P < 0.05). Apoptosis and the relative protein expression of B-cell lymphoma-2-associated X and cleaved Caspase3 were decreased (P < 0.05). Autophagy-related molecules such as phosphorylated unc-51-like autophagy-activating kinase 1 (Ser757) and p62 were decreased. Beclin1, microtubule-associated protein 1 light chain 3 A/B, and autophagosomes were increased (P < 0.05). Besides, the phosphatidylinositol 3-kinase/AKT/mammalian target of rapamycin signaling pathway, as a negative regulator of autophagy to some degree, was inhibited. This study revealed that vacuum therapy ameliorated pPED in BCNC rats by inhibiting apoptosis and activating autophagy.
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