哌嗪阿魏酸盐对糖尿病诱发的睾丸功能障碍的影响:揭示遗传学观点、MAPK/ERK/JNK 途径和 TGF-β 信号传导。

IF 3.1 4区 医学 Q2 PHARMACOLOGY & PHARMACY
Basel A Abdel-Wahab, Ehab A M El-Shoura, Mohammed S Habeeb, Nayef A Aldabaan, Yasmine H Ahmed, Dalia Zaafar
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引用次数: 0

摘要

糖尿病性睾丸功能障碍(DTD)严重威胁男性生殖健康。本研究探讨了天然酚类化合物阿魏酸哌嗪(piperazine ferulate, PF)缓解DTD的潜力,并揭示了其在大鼠中的潜在机制。动物分为对照组、PF组、糖尿病组和糖尿病+ PF组。大鼠单次腹腔注射链脲佐菌素(STZ) 50 mg/kg诱导糖尿病。给药剂量为50mg /kg/d, ig注射,连续4周。糖尿病大鼠的性行为发生了显著变化,同时血清睾酮、卵泡刺激素和黄体生成素水平也有所降低。精子数量、活力、活力和形态的异常伴随着与精子发生相关的基因和蛋白质表达的抑制而发生。组织病理学检查显示精小管萎缩,胚芽和间质细胞广泛变性和坏死。给药后糖尿病大鼠睾丸功能明显改善,睾丸组织学正常,睾酮水平升高,精子质量提高。除了降低炎症因子、COX2和NF-κB的表达外,pf还提高了抗氧化水平和Nrf2/HO-1的表达。此外,PF调控睾丸变性的关键信号通路,通过激活TGF-β保护性信号通路,减弱MAPK/ERK/JNK信号级联,促进细胞存活和组织修复,从而减少炎症和细胞凋亡。PF抑制了INSL3、SPHK1、CD62E、ANGPTL2和miR-148a-5p的表达,同时增加了睾丸基因如HSD17B1、DAZL和S1P的表达,解决了DTD。这项研究强调了PF通过调节遗传和信号通路来恢复糖尿病男性睾丸功能和生育能力的潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Piperazine ferulate impact on diabetes-induced testicular dysfunction: unveiling genetic insights, MAPK/ERK/JNK pathways, and TGF-β signaling.

Diabetic testicular dysfunction (DTD) poses a significant threat to male reproductive health. This study delves into the potential of piperazine ferulate (PF), a natural phenolic compound, in alleviating DTD and sheds light on its underlying mechanisms in rats. Animals were divided into the control, PF, diabetic, and diabetic plus PF groups. Diabetes was induced in rats with a single intraperitoneal (i.p.) injection of streptozotocin (STZ) at 50 mg/kg. PF was administered at 50 mg/kg/day via i.p. injection for four weeks. Significant changes in sexual behavior were observed in diabetic rats, which additionally revealed lower serum levels of testosterone, FSH, and LH. The abnormalities in sperm count, viability, motility, and morphology occurred along with the demonstrated suppression of genes and protein expression related to spermatogenesis. Atrophy of the seminiferous tubules and extensive degeneration and necrosis of the germ and Leydig cells were highlighted by histopathological examination. The testicular function of diabetic rats was significantly improved after PF administration, evidenced by normalized testicular histology, increased testosterone levels, and enhanced sperm quality. In addition to reducing inflammatory cytokines, COX2, and NF-κB expression, pf administration elevated the antioxidant levels and Nrf2/HO-1 expression. Furthermore, key signaling pathways involved in testicular degeneration are regulated by PF. It promoted cell survival and tissue repair by activating the protective TGF-β signaling pathway and attenuating the MAPK/ERK/JNK signaling cascade, which in turn reduced inflammation and apoptosis. PF suppressed the expression of INSL3, SPHK1, CD62E, ANGPTL2, and miR-148a-5p, while increasing the expression of testicular genes like HSD17B1, DAZL, and S1P, addressing DTD. This study highlights the potential of PF to restore testicular function and fertility in diabetic males by modulating genetic and signaling pathways.

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来源期刊
CiteScore
6.20
自引率
5.60%
发文量
142
审稿时长
4-8 weeks
期刊介绍: Naunyn-Schmiedeberg''s Archives of Pharmacology was founded in 1873 by B. Naunyn, O. Schmiedeberg and E. Klebs as Archiv für experimentelle Pathologie und Pharmakologie, is the offical journal of the German Society of Experimental and Clinical Pharmacology and Toxicology (Deutsche Gesellschaft für experimentelle und klinische Pharmakologie und Toxikologie, DGPT) and the Sphingolipid Club. The journal publishes invited reviews, original articles, short communications and meeting reports and appears monthly. Naunyn-Schmiedeberg''s Archives of Pharmacology welcomes manuscripts for consideration of publication that report new and significant information on drug action and toxicity of chemical compounds. Thus, its scope covers all fields of experimental and clinical pharmacology as well as toxicology and includes studies in the fields of neuropharmacology and cardiovascular pharmacology as well as those describing drug actions at the cellular, biochemical and molecular levels. Moreover, submission of clinical trials with healthy volunteers or patients is encouraged. Short communications provide a means for rapid publication of significant findings of current interest that represent a conceptual advance in the field.
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