己酮可可碱通过上调 Nrf2-ARE 信号通路促进生精作用在睾丸扭转复位诱导的生精细胞凋亡的小鼠模型中。

Pentoxifylline promotes spermatogenesis via upregulation of the Nrf2-ARE signalling pathway in a mouse model of germ-cell apoptosis induced by testicular torsion-detorsion.

机构信息

Department of Anatomy, Faculty of Basic Medical Sciences, Olabisi Onabanjo University, Sagamu, Ogun State, Nigeria.

Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

出版信息

Reprod Fertil Dev. 2023 Apr;35(7):423-432. doi: 10.1071/RD22168.

DOI:10.1071/RD22168

PMID:37062868

Abstract

CONTEXT

Testicular torsion-detorsion results in loss of germ cells and infertility. Pentoxifylline has been shown to prevent tissue damage.

AIMS

To determine the effect of pentoxifylline on germ cell survival in torsion-detorsion induced apoptosis Methods: Twenty male mice were divided into four groups of five animals each: Control, T1 (Torsion-detorsion+single dose 100mg/kg Pentoxifylline/IP), T2 (Torsion-detorsion+daily 20mg/kg pentoxifylline/IP for 2weeks, and T/D (Torsion-detorsion only). 35thday after torsion-detorsion, the left testes of all the animals were harvested for histological and biochemical analysis.

KEY RESULTS

Histomorpholoical analysis showed significant increase (P <0.05) in seminiferous tubule diameter, Johnsen's score and germ cells of Control and T1 compared to T2 and T/D, with no significant difference (P >0.05) in testis weight, sertoli, leydig and myoid cells. Tunnel assay showed significant increase (P <0.05) in apoptotic cells of T/D and T2 animals compared to Control and T1. RT-PCR analysis showed significant high (P <0.01) mRNA expression of Bax gene in T/D compared to T1 and T2 and significant increase (P <0.05) of Bcl2 in Control, T1, T2 compared to T/D. Nrf2-ARE transcripts revealed significant increase (P <0.05) in Control and T1 compared to T2 and T/D. Western blot showed significantly increased (P <0.05) caspase-3 in T/D compared to Control, T1 and T2.

CONCLUSION

Pentoxifylline promotes spermatogenesis and suppressed apoptosis induced by testicular torsion-detorsion.

IMPLICATION

Pentoxifylline could serve as adjunct therapy to surgery in the treatment of torsion-detorsion induced germ cell apoptosis.

摘要

背景

睾丸扭转-复位会导致生殖细胞丢失和不育。己酮可可碱已被证明可防止组织损伤。

目的

确定己酮可可碱对扭转-复位诱导细胞凋亡中生殖细胞存活的影响。

方法

将 20 只雄性小鼠分为 4 组，每组 5 只：对照组、T1 组（扭转-复位+单次 100mg/kg 己酮可可碱/腹腔注射）、T2 组（扭转-复位+每日 20mg/kg 己酮可可碱/腹腔注射 2 周，和 T/D 组（仅扭转-复位）。扭转-复位后 35 天，所有动物的左侧睾丸均用于组织学和生化分析。

主要结果

组织形态学分析显示，与 T2 和 T/D 相比，Control 和 T1 组的生精小管直径、Johnsen 评分和生殖细胞显著增加（P <0.05），而睾丸重量、Sertoli、Leydig 和肌样细胞无显著差异（P >0.05）。隧道试验显示，与 Control 和 T1 相比，T/D 和 T2 动物的凋亡细胞显著增加（P <0.05）。RT-PCR 分析显示，与 T1 和 T2 相比，T/D 组 Bax 基因的 mRNA 表达显著升高（P <0.01），Control、T1、T2 组的 Bcl2 表达显著升高（P <0.05）与 T/D 相比。Nrf2-ARE 转录物显示 Control 和 T1 组与 T2 和 T/D 组相比显著增加（P <0.05）。Western blot 显示 T/D 组 caspase-3 显著增加（P <0.05）与 Control、T1 和 T2 相比。