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谷氨酰胺可预防缺血/再灌注诱导的睾丸损伤中 NF-κB 信号转导和 caspase 3 激活的上调:动物模型。

Glutamine prevents upregulation of NF-kB signaling and caspase 3 activation in ischaemia/reperfusion-induced testicular damage: An animal model.

机构信息

Department of Physiology, Ladoke Akintola University of Technology, Ogbomoso, Oyo State, Nigeria.

Department of Veterinary Pathology and Microbiology, University of Nigeria, Nsukka, Nigeria.

出版信息

Biomed Pharmacother. 2022 Jun;150:113056. doi: 10.1016/j.biopha.2022.113056. Epub 2022 May 1.

DOI:10.1016/j.biopha.2022.113056
PMID:35658227
Abstract

AIM

Testicular ischaemia/reperfusion (I/R) injury is a major consequence of testicular torsion with possible attendant risk of male infertility. Glutamine, on the other hand, is a known antioxidant with anti-inflammatory potential. The present study evaluated whether or not glutamine would improve I/R-induced testicular injury in torsion/detorsion (T/D). The possible associated mechanisms were also investigated.

METHODS

Wistar rats were randomly allotted into four groups (n = 10); sham-operated, glutamine-treated, T/D, and T/D + glutamine. Testicular torsion was induced and reperfusion established after two and a half hour under ketamine/xylazine anaethesia. Glutamine was administered one hour before reperfusion and continued daily for 3 days. At the end of the study, animals were euthanized, blood samples obtained, epididymal sperm suspension collected, and the testes harvested for biochemical and histopathological assays using established methods.

RESULTS

Glutamine prevented T/D-driven I/R-induced reduced sperm quality, impaired testicular histoarchitecture, and suppressed circulating testosterone. Also, glutamine abated I/R-induced oxidative stress (evidenced by reduced hydrogen peroxide and MDA generation and enhanced concentrations and activities of antioxidants), inflammation (evidenced by suppression of TNF-α and IL-1β), and apoptosis (evidenced by reduced DNA fragmentation) by down-regulating NF-kB and caspase 3 activity.

CONCLUSION

For the first time, this study demonstrated that glutamine administration improved testicular I/R injury in T/D rat model by maintaining testicular redox balance, and testicular integrity and function via inhibition of I/R-induced upregulation of NF-kB signaling and caspase 3 activation.

摘要

目的

睾丸缺血/再灌注(I/R)损伤是睾丸扭转的主要后果,可能伴有男性不育的风险。另一方面,谷氨酰胺是一种已知的抗氧化剂,具有抗炎潜力。本研究评估了谷氨酰胺是否会改善扭转/复位(T/D)引起的 I/R 睾丸损伤。还研究了可能的相关机制。

方法

将 Wistar 大鼠随机分为四组(n=10);假手术、谷氨酰胺治疗、T/D 和 T/D+谷氨酰胺。在氯胺酮/甲苯噻嗪麻醉下诱导睾丸扭转,2.5 小时后恢复灌注。谷氨酰胺在再灌注前 1 小时给药,并连续给药 3 天。研究结束时,处死动物,采集血液样本,收集附睾精子悬液,并采集睾丸进行生化和组织病理学检测,方法如下。

结果

谷氨酰胺预防了 T/D 引起的 I/R 诱导的精子质量下降、睾丸组织形态结构受损和循环睾酮水平降低。此外,谷氨酰胺减轻了 I/R 引起的氧化应激(表现为减少过氧化氢和 MDA 的产生,增加抗氧化剂的浓度和活性)、炎症(表现为 TNF-α和 IL-1β的抑制)和凋亡(表现为 DNA 片段化减少),通过下调 NF-kB 和 caspase 3 的活性。

结论

本研究首次表明,谷氨酰胺给药通过维持睾丸氧化还原平衡和睾丸完整性和功能,改善 T/D 大鼠模型中的睾丸 I/R 损伤,抑制 I/R 诱导的 NF-kB 信号转导和 caspase 3 激活。

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