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没食子酸通过调节NF-κB和PK2/PKR1通路减轻脂多糖诱导的睾丸炎症。

Gallic acid mitigates lipopolysaccharide-induced testicular inflammation via regulation of the NF-κB and PK2/PKR1 pathway.

作者信息

Delen Ozlem, Uz Yesim Hulya, Yuksel Cengiz, Ersoy Onur, Kizilay Gulnur

机构信息

Department of Histology and Embryology, Faculty of Medicine, Trakya University, Edirne, 22030, Turkey.

Department of Pathology Laboratory Techniques, Vocational School of Health Services, Trakya University, Edirne, Turkey.

出版信息

J Mol Histol. 2025 Jan 18;56(1):71. doi: 10.1007/s10735-024-10349-4.

DOI:10.1007/s10735-024-10349-4
PMID:39825958
Abstract

Genital tract infections are common causes of male infertility, and most of diagnosed men are asymptomatic. This study examined the effect of gallic acid (GA) against lipopolysaccharide (LPS)-induced testicular inflammation. Thirty-two Spraque Dawley, 2.5-3 month-old male rats were separated into four groups (n = 8). Control group; saline at 3 ml/kg, and in the GA group; GA was dissolved in saline, by gavage at 100 mg/kg for 14 days. LPS group; LPS 5 mg/kg as a single dose was given intraperitoneal on the 11th day. LPS + GA group; GA was given for 14 days and LPS 5 mg/kg on the 11th day. After 72 h of LPS injection, all samples were collected. Semen analysis, biochemical assays, histological evaluations, and immunohistochemical or Western blot analyses for nuclear factor-kappa B (NF-κB) and Prokineticin 2/prokineticin receptor 1(PK2/PKR1) pathways were performed. There was a significant decrease in body and testicular weight, sperm parameters, serum testosterone level, mean seminiferous tubule diameter, germinal epithelial thickness, and Johnsen score in the LPS group compared to control and GA groups. However, a significant increase was found in interstitial space width, percentage of abnormal sperm, NF-κB and PK2 immunoreactivities, and expression of PK2 and PKR1 proteins. In the LPS + GA group, GA administration was observed to significantly prevent these adverse effects. In conclusion, the inhibitory effects of GA on the NF-κB and PK2/PKR1 pathways not only suppressed the inflammatory response but also restored impaired sperm parameters and testicular structure. These findings indicate GA's potential for treating testicular inflammation and protecting male reproductive health.

摘要

生殖道感染是男性不育的常见原因,大多数被诊断出的男性没有症状。本研究考察了没食子酸(GA)对脂多糖(LPS)诱导的睾丸炎症的影响。将32只2.5 - 3月龄的Spraque Dawley雄性大鼠分为四组(n = 8)。对照组;按3 ml/kg给予生理盐水,GA组;GA溶解于生理盐水中,以100 mg/kg的剂量灌胃给药14天。LPS组;在第11天腹腔注射单次剂量5 mg/kg的LPS。LPS + GA组;GA给药14天,并在第11天给予5 mg/kg的LPS。注射LPS 72小时后,收集所有样本。进行精液分析、生化测定、组织学评估以及针对核因子-κB(NF-κB)和促动力蛋白2/促动力蛋白受体1(PK2/PKR1)途径的免疫组织化学或蛋白质印迹分析。与对照组和GA组相比,LPS组的体重、睾丸重量、精子参数、血清睾酮水平、平均曲细精管直径、生精上皮厚度和约翰森评分显著降低。然而,间质间隙宽度、异常精子百分比、NF-κB和PK2免疫反应性以及PK2和PKR1蛋白的表达显著增加。在LPS + GA组中,观察到GA给药可显著预防这些不良反应。总之,GA对NF-κB和PK2/PKR1途径的抑制作用不仅抑制了炎症反应,还恢复了受损的精子参数和睾丸结构。这些发现表明GA在治疗睾丸炎症和保护男性生殖健康方面具有潜力。

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