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犬睾丸组织中问号钩端螺旋体感染的细胞病理生理学:TLR4/NF-κB/JNK信号通路的作用

Cellular pathophysiology of Leptospira interrogans infection in canine testicular tissue: role of the TLR4/NF-kB/JNK pathway.

作者信息

Bolat İsmail, Bolat Merve, Kiliçlioğlu Metin, Yıldırım Serkan, Sağlam Yavuz S, Çomaklı Selim, Gözegir Berrah

机构信息

Department of Pathology, Faculty of Veterinary Medicine, Atatürk University, 25240 Erzurum, Türkiye.

Department of Physiology, Faculty of Veterinary Medicine, Atatürk University, 25240 Erzurum, Türkiye.

出版信息

J Comp Pathol. 2025 Jan;216:10-19. doi: 10.1016/j.jcpa.2024.11.001. Epub 2024 Dec 9.

Abstract

Leptospirosis is a prevalent zoonotic disease in dogs. Although it is known that leptospires are primarily harboured in kidney tissues of dogs, it has been reported that they also infect testicular tissue. Leptospira interrogans causes various lesions in canine testicular tissues; however, the pathogenesis has not been clearly explained. In this study, 20 canine testicular tissue samples infected with L. interrogans were investigated for evidence of oxidative DNA damage, inflammation, apoptosis and autophagy. Ten samples of canine testicular tissue that were negative for L. interrogans were used as a positive control group. All tissues were examined by histopathological, immunohistochemistry (IHC) and immunofluorescence (IF) methods. Histopathological examination revealed that testicular tissues infected with L. interrogans had inflammation and oedema, and degeneration and necrosis of spermatocytes. In cases of severe disease, enzyme-linked immunosorbent assay, reverse transcriptase polymer chain reaction and IHC and IF indicated significant increases in levels of TLR4, NF-kB, IL-1β, TNF-α, 8-OHdG, JNK1/3, caspase-8, caspase-3, LC3A and LC3B but lower levels in milder cases. These results indicate that L. interrogans stimulated the immune system through the TLR4/NF-kB/JNK pathway in dog testicular tissues, leading to inflammation and apoptosis. The infection also caused oxidative DNA damage and autophagy.

摘要

钩端螺旋体病是犬类中一种普遍的人畜共患病。虽然已知钩端螺旋体主要寄生于犬类的肾脏组织中,但也有报道称它们会感染睾丸组织。问号钩端螺旋体在犬类睾丸组织中会引发各种病变;然而,其发病机制尚未得到明确解释。在本研究中,对20份感染问号钩端螺旋体的犬类睾丸组织样本进行了氧化DNA损伤、炎症、凋亡和自噬证据的调查。将10份问号钩端螺旋体检测呈阴性的犬类睾丸组织样本用作阳性对照组。所有组织均通过组织病理学、免疫组织化学(IHC)和免疫荧光(IF)方法进行检查。组织病理学检查显示,感染问号钩端螺旋体的睾丸组织出现炎症和水肿,以及精母细胞的变性和坏死。在重症病例中,酶联免疫吸附测定、逆转录聚合酶链反应以及IHC和IF表明,TLR4、NF-κB、IL-1β、TNF-α、8-OHdG、JNK1/3、半胱天冬酶-8、半胱天冬酶-3、LC3A和LC3B水平显著升高,但轻症病例中这些水平较低。这些结果表明,问号钩端螺旋体通过犬类睾丸组织中的TLR4/NF-κB/JNK途径刺激免疫系统,导致炎症和凋亡。该感染还会引起氧化DNA损伤和自噬。

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