背景:睾丸扭转/扭曲可导致睾丸丢失和不育。苦豆碱是从苦豆子中提取的一种主要活性生物碱。它已被证明具有器官保护作用。然而,aloperine对睾丸的影响及其潜在机制尚不清楚.
目的:本研究探讨苦豆素对大鼠睾丸扭转/扭转损伤的影响。
方法:雄性Sprague-Dawley大鼠随机分为假手术(sham),睾丸I/R(TI/R),或aloperine预处理(ALOPre)或后处理(ALOPost)组。除假手术大鼠外,所有大鼠均接受3h的右精索扭转(720°,顺时针),然后是3小时的扭曲。在睾丸扭转之前(ALOPre)或在睾丸扭曲发作时(ALOPost)静脉内施用阿洛培林(10mg/kg)。通过组织学分析评估aloperine的治疗效果,氧化应激评估,炎症反应检查,细胞凋亡分析,蛋白质分析,和免疫组织学评估。
结果:与TI/R相比,aloperine保护同侧和对侧睾丸免受单侧睾丸I/R,如睾丸重量与体重(TW/BW)之比(ALOPre:p=0.0037;ALOPost:p=0.0021)和体积(ALOPre:p=0.0020;ALOPost:p=0.0009)所证明,使用更好的Johnsen(ALOPre:p=0.0013;ALOPost:p=0.0021),和Cosentino分数(ALOPre:p<0.0001;ALOPost:p<0.0001),平均生精管直径和平均生精管上皮高度增加,睾丸细胞凋亡减少,和较少的氧化应激和炎症反应。此外,aloperine显着刺激了同侧睾丸中信号转导和转录激活因子(STAT)-3的磷酸化。施用Ag490抑制STAT-3磷酸化,从而消除了aloperine对同侧睾丸的保护作用。
结论:Aloperine对睾丸扭转/扭转后的同侧和对侧睾丸有较强的保护作用。这种羟色胺诱导的同侧睾丸保护作用是通过STAT-3信号通路介导的。
BACKGROUND: Testicular torsion/detorsion can cause testis loss and infertility. Aloperine is a major active alkaloid extracted from Sophora alopecuroides Linn. It has been shown to have organ-protective effects. However, the effects of aloperine on the testis and its underlying mechanisms remain unclear.
OBJECTIVE: This study investigated the effect of aloperine on testicular torsion/detorsion injury in rats.
METHODS: Male Sprague-Dawley rats were randomized to the sham-operated (sham), testicular I/R (TI/R), or aloperine preconditioning (ALOPre) or postconditioning (ALOPost) groups. All rats except for the sham-operated rats were subjected to 3 h of right spermatic cord torsion (720°, clockwise), followed by 3 h of detorsion. Aloperine (10 mg/kg) was intravenously administered before testicular torsion (ALOPre) or at the onset of testicular detorsion (ALOPost). The therapeutic efficacy of aloperine was evaluated by histological analysis, oxidative stress evaluation, inflammatory response examination, apoptosis analysis, protein analysis, and immunohistological assessment.
RESULTS: Compared with TI/R, aloperine protected both the
ipsilateral and contralateral testes against unilateral testicular I/R, as evidenced by a reduced testicular weight to body weight (TW/BW) ratio (ALOPre: p = 0.0037; ALOPost: p = 0.0021) and volume (ALOPre: p = 0.0020; ALOPost: p = 0.0009), less structural damage with better Johnsen (ALOPre: p = 0.0013; ALOPost: p = 0.0021), and Cosentino scores (ALOPre: p < 0.0001; ALOPost: p < 0.0001), increased mean seminiferous tubule diameter and mean seminiferous tubule epithelial height, decreased testicular apoptosis, and less oxidative stress and inflammatory response. In addition, aloperine significantly stimulated the phosphorylation of signal transducer and activator of transcription (STAT)-3 in the
ipsilateral testes following detorsion. Administration of Ag490 suppressed STAT-3 phosphorylation, thereby abrogating the protective effects exerted by aloperine on the
ipsilateral testis.
CONCLUSIONS: Aloperine has a strong testicular protective effect on the
ipsilateral and contralateral testes after testicular torsion/detorsion. This aloperine-induced
ipsilateral testicular protection is mediated via the STAT-3 signaling pathway.