Spexin peptide ameliorates renal injury in diabetic nephropathy rat model via modulation of metabolic, oxidative, inflammatory, and apoptotic dysregulations.

IF 3.7 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Hadeel Elsherbiny, Sulaiman Mohammed Alnasser, Mohamed Aref, Esraa ElSheikh, Sherein F El-Sayed, Nanees F El-Malkey, Haifa A Alqahtani, Abdullah A A Alghamdi, Mohamed A Nassan, Hanan H Abd-ELhafeez, Gamal A Salem
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Abstract

Diabetic nephropathy is recognized as the predominant cause of end-stage renal disease worldwide. In reaction to metabolic stress, the peptide hormone spexin-14, is synthesized in both central and peripheral tissues. Its level is reduced in type II diabetes mellites and may play a role in glucose metabolism. However, in the context of DN, the mechanisms through which spexin exerts its effects remain largely unknown. This research employed a rat model of DN to explore the therapeutic potential and the underlying mechanisms associated with spexin treatment. For the development of this experimental model, rats were subjected to an eight-week regimen of a high-fat, high-fructose diet prior to receiving a single dose of streptozotocin (35 mg/kg body weight). Subsequently, spexin was administered subcutaneously on a daily basis for a duration of eight weeks at a dosage of 50 µg/kg body weight. The evaluation methods employed encompassed renal function assessments, macromorphological examinations, histopathological evaluations, and analyses of inflammatory and oxidative stress mediators. Additionally, immunohistochemical staining for NF-kB and E-cadherin, along with PCR analysis of mTOR, Bcl2, and Bax gene expressions in renal tissues, were conducted. Following the administration of spexin to the diabetic rats, there was a significant reduction in serum levels of glucose, urea, creatinine, and inflammatory cytokines (IL-1β, TNF-α), alongside a marked restoration of antioxidant enzyme activities. Furthermore, a significant decline in the levels of NF-κB, mTOR, and Bax was noted and accompanied with increased expressions of Bcl-2 and E-cadherin proteins. The observed improvements in histopathological changes significantly corroborated the biochemical results. In summary, spexin has proven to be effective in alleviating DN by its capacity to mitigate metabolic disturbances, oxidative stress, inflammation, and apoptosis.

Spexin肽通过调节代谢、氧化、炎症和凋亡失调改善糖尿病肾病大鼠模型的肾损伤。
糖尿病肾病被公认为终末期肾脏疾病的主要原因。在代谢应激的作用下,中枢和外周组织都会合成肽激素spexin-14。它的水平在II型糖尿病患者中降低,可能在葡萄糖代谢中起作用。然而,在DN的背景下,spexin发挥其作用的机制在很大程度上仍然未知。本研究采用大鼠DN模型,探讨spexin治疗的治疗潜力及其相关机制。为了建立这个实验模型,大鼠在接受单剂量链脲佐菌素(35 mg/kg体重)之前,进行了为期8周的高脂肪、高果糖饮食。随后,以50µg/kg体重的剂量每日皮下给药spexin,持续8周。评估方法包括肾功能评估、大形态学检查、组织病理学评估以及炎症和氧化应激介质分析。此外,进行NF-kB和E-cadherin的免疫组化染色,以及肾组织中mTOR、Bcl2和Bax基因表达的PCR分析。糖尿病大鼠服用spexin后,血清葡萄糖、尿素、肌酐和炎症细胞因子(IL-1β、TNF-α)水平显著降低,同时抗氧化酶活性显著恢复。此外,NF-κB、mTOR和Bax水平显著下降,并伴有Bcl-2和E-cadherin蛋白表达升高。观察到的组织病理学变化的改善显著证实了生化结果。综上所述,spexin通过其减轻代谢紊乱、氧化应激、炎症和细胞凋亡的能力,已被证明能有效缓解DN。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Journal of physiology and biochemistry
Journal of physiology and biochemistry 生物-生化与分子生物学
CiteScore
6.60
自引率
0.00%
发文量
86
审稿时长
6-12 weeks
期刊介绍: The Journal of Physiology and Biochemistry publishes original research articles and reviews describing relevant new observations on molecular, biochemical and cellular mechanisms involved in human physiology. All areas of the physiology are covered. Special emphasis is placed on the integration of those levels in the whole-organism. The Journal of Physiology and Biochemistry also welcomes articles on molecular nutrition and metabolism studies, and works related to the genomic or proteomic bases of the physiological functions. Descriptive manuscripts about physiological/biochemical processes or clinical manuscripts will not be considered. The journal will not accept manuscripts testing effects of animal or plant extracts.
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