TNF-α antagonist alleviates muscular layer enlargement but does not prevent myenteric neuronal loss in the colon of streptozotocin-induced diabetic rats

IF 2 3区医学 Q2 ANATOMY & MORPHOLOGY

Annals of Anatomy-Anatomischer Anzeiger Pub Date : 2025-04-26 DOI:10.1016/j.aanat.2025.152666

Tri Agusti Sholikah , Dian Eurike Septyaningtrias , Yustina Andwi Ari Sumiwi , Muthmainah Muthmainah , Jens Randell Nyengaard , Rina Susilowati

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Abstract

Background

this study aimed to examine the impact of a TNF-α antagonist on markers of neuronal death, the total number of myenteric neurons, and the volume of each colonic layer in diabetic rats.

Methods

thirty male rats were divided into normal control (NC), diabetic control (DC), and diabetic etanercept (DE) groups. Diabetes was induced using streptozotocin and nicotinamide. The DE group received twice-weekly injections of etanercept. Immunohistochemistry staining and western blotting detected activated caspase-3, Gasdermin D, and phosphorylated-MLKL. Stereological methods were performed in colon sections stained with Toluidine-blue to estimate the total number of neurons in the colonic myenteric plexus and the colonic layer volume.

Results

immunohistochemistry showed etanercept reduced expression of apoptosis and pyroptosis markers, but not necroptosis, in the myenteric plexus of the colon in diabetic rats. Diabetic rats exhibited a lower total number of neurons in the colonic myenteric ganglions, and etanercept did not prevent this neuronal loss. Furthermore, colonic layer enlargement was observed in diabetic rats, with only the muscular layer hypertrophy being prevented by etanercept administration.

Conclusions

the TNF-α antagonist did not prevent neuronal loss in the colonic myenteric plexus; it partially inhibited colonic muscular layer enlargement in diabetic rats.

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TNF-α拮抗剂减轻了链脲霉素诱导的糖尿病大鼠的肌肉层扩大，但不能防止结肠肌肠神经元的损失

本研究旨在研究TNF-α拮抗剂对糖尿病大鼠神经元死亡标志物、肌肠神经元总数和各结肠层体积的影响。方法将30只雄性大鼠分为正常对照组（NC）、糖尿病对照组（DC）和糖尿病依那西普组（DE）。采用链脲佐菌素和烟酰胺诱导糖尿病。DE组每周注射依那西普2次。免疫组织化学染色和western blotting检测到活化的caspase-3、Gasdermin D和磷酸化的mlkl。以甲苯胺蓝染色结肠切片，用体视学方法估计结肠肌丛神经元总数和结肠层体积。结果免疫组化结果显示依那西普能降低糖尿病大鼠结肠肌丛细胞凋亡和焦亡标志物的表达，但不能降低坏死的表达。糖尿病大鼠在结肠肌肠神经节中表现出较低的神经元总数，依那西普不能防止这种神经元的损失。此外，在糖尿病大鼠中观察到结肠层扩大，只有肌肉层肥大被依那西普预防。结论TNF-α拮抗剂并不能预防结肠肌丛神经元的丢失；部分抑制糖尿病大鼠结肠肌层扩大。

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

Annals of Anatomy-Anatomischer Anzeiger 医学-解剖学与形态学

CiteScore

4.40

自引率

22.70%

发文量

137

审稿时长

33 days

期刊介绍： Annals of Anatomy publish peer reviewed original articles as well as brief review articles. The journal is open to original papers covering a link between anatomy and areas such as •molecular biology, •cell biology •reproductive biology •immunobiology •developmental biology, neurobiology •embryology as well as •neuroanatomy •neuroimmunology •clinical anatomy •comparative anatomy •modern imaging techniques •evolution, and especially also •aging