Testicular torsion and detorsion (TTD) is a serious urological condition affecting young males that is underlined by an ischemia reperfusion injury (tIRI) to the testis as the pathophysiological mechanism. During tIRI, uncontrolled production of oxygen reactive species (ROS) causes DNA damage leading to germ cell apoptosis (GCA). The aim of the study is to explore whether inhibition of NADPH oxidase (NOX), a major source of intracellular ROS, will prevent tIRI-induced GCA and its association with endoplasmic reticulum (ER) stress. Sprague-Dawley rats (n = 36) were divided into three groups: sham, tIRI only and tIRI treated with apocynin (a NOX inhibitor). Rats undergoing tIRI endured an ischemic injury for 1 h followed by 4 h of reperfusion. Spermatogenic damage was evaluated histologically, while cellular damages were assessed using real time PCR, immunofluorescence staining, Western blot and biochemical assays. Disrupted spermatogenesis was associated with increased lipid and protein peroxidation and decreased antioxidant activity of the enzyme superoxide dismutase (SOD) as a result of tIRI. In addition, increased DNA double strand breaks and formation of 8-OHdG adducts associated with increased phosphorylation of the DNA damage response (DDR) protein H2AX. The ASK1/JNK apoptosis signaling pathway was also activated in response to tIRI. Finally, increased immuno-expression of the unfolded protein response (UPR) downstream targets: GRP78, eIF2-α1, CHOP and caspase 12 supported the presence of ER stress. Inhibition of NOX by apocynin protected against tIRI-induced GCA and ER stress. In conclusion, NOX inhibition minimized tIRI-induced intracellular oxidative damages leading to GCA and ER stress.

睾丸扭转和扭曲（TTD）是一种严重的泌尿外科疾病，影响年轻男性，其病理生理机制是睾丸缺血再灌注损伤（tIRI）突显出这一现象。在tIRI期间，不受控制的氧反应性物质（ROS）的产生会导致DNA损伤，从而导致生殖细胞凋亡（GCA）。该研究的目的是探讨抑制细胞内ROS的主要来源NADPH氧化酶（NOX）是否会预防tIRI诱导的GCA及其与内质网（ER）应激的关系。Sprague-Dawley大鼠（n = 36）分为三组：假手术，仅tIRI和用apocynin（一种NOX抑制剂）治疗的tIRI。接受tIRI的大鼠遭受缺血性损伤1小时，然后再灌注4小时。通过组织学评估生精损伤，同时使用实时PCR评估细胞损伤，免疫荧光染色，蛋白质印迹和生化分析。由于tIRI，精子发生紊乱与脂质和蛋白质过氧化作用增加以及超氧化物歧化酶（SOD）的抗氧化活性降低有关。此外，与DNA损伤反应（DDR）蛋白H2AX的磷酸化增加有关的DNA双链断裂增加和8-OHdG加合物的形成。ASK1 / JNK细胞凋亡信号通路也响应tIRI而被激活。最后，未折叠的蛋白质应答（UPR）下游靶标（GRP78，eIF2-α1，CHOP和caspase 12）的免疫表达增加支持ER应激的存在。载有Apocynin的NOx抑制作用可抵抗tIRI诱导的GCA和ER应激。结论，