Department of Anatomy, College of Medicine, Taibah University, Madinah, Saudi Arabia.
Folia Morphol (Warsz). 2023;82(3):641-655. doi: 10.5603/FM.a2022.0071. Epub 2022 Aug 2.
Cellular inflammatory processes, fibrogenesis, and apoptosis are the most characteristic pathologic features of colonic injury and colitis in human and experimental animals. Obestatin, a peptide derived from proghrelin, is reported to have significant protective and curative actions on many gastrointestinal tract inflammatory diseases, including ulcerative colitis. However, its exact protective mechanisms and the associated histopathological changes, are still in need of deeper exploration. This study explores the effect of obestatin on the course of acetic acid (AA)-induced colitis as an antifibrotic, anti-inflammatory, and anti-apoptotic agent in relation to associated tissue stress parameters.
A total of 40 healthy male albino Wistar rats weighing 200-250 g were recruited in this study. The rats were classified into four groups (10 rats each); group I: control, group II: obestatin only treated (16 nmol/kg), group III: colitis induced group (AA 1 mL of 3.5% (v/v), and group IV: AA-induced colitis + obestatin for 14 days. Colonic samples were examined after staining haematoxylin and eosin, Alcian blue, Masson trichrome. The expression of proliferating cell nuclear antigen (PCNA), nuclear factor kappa B (NFkB), and caspase-3 was estimated after immunohistochemical staining. Oxidative stress parameters, antioxidant enzymes, tissue myeloperoxidase (MPO) activity, ghrelin, and fibrogenesis markers were identified by immunoassay and colorimetric techniques.
Colonic mucosa of group IV exhibited mucosal healing and regeneration of the surface epithelium with the restoration of the goblet cells' function together with a decline in PCNA, NFkB, and caspase-3 immunoreactivity in comparison to group III. This was accompanied by a reduction of the expression of fibrosis markers, hydroxyproline and fibronectin. In addition, tissue antioxidant status was significantly improved with a marked reduction of tissue MPO. Ghrelin level was significantly increased in comparison to group III. Group IV exhibited significant reduction in the levels of oxidative stress markers, malondialdehyde, total oxidant status with a marked increase in the activity of antioxidant enzymes, superoxide dismutase, catalase, and total cellular total antioxidant capacity.
The concomitant treatment of obestatin inhibits the development of AA-induced colitis. The data signify that it has both curative and protective effects via antifibrotic, antioxidant, and anti-inflammatory activities.
细胞炎症过程、纤维化和细胞凋亡是人类和实验动物结肠损伤和结肠炎的最典型病理特征。肥胖抑制素是一种源于前胃饥饿素的肽，据报道，它对许多胃肠道炎症性疾病，包括溃疡性结肠炎，具有显著的保护和治疗作用。然而，其确切的保护机制和相关的组织病理学变化仍需要更深入的探索。本研究探讨了肥胖抑制素作为一种抗纤维化、抗炎和抗凋亡剂，在与相关组织应激参数相关的情况下，对乙酸（AA）诱导的结肠炎的影响。
本研究共招募了 40 只体重为 200-250 克的健康雄性白化 Wistar 大鼠。这些大鼠被分为四组（每组 10 只）；第 I 组：对照组；第 II 组：仅给予肥胖抑制素处理（16 nmol/kg）；第 III 组：诱导结肠炎组（AA 1 mL 的 3.5%（v/v））；第 IV 组：AA 诱导结肠炎+肥胖抑制素治疗 14 天。用苏木精和伊红、阿利新蓝、马松三色染色后检查结肠样本。用免疫组织化学染色法估计增殖细胞核抗原（PCNA）、核因子 kappa B（NFkB）和半胱天冬酶-3 的表达。通过免疫测定和比色技术鉴定氧化应激参数、抗氧化酶、组织髓过氧化物酶（MPO）活性、胃饥饿素和纤维化标志物。
与第 III 组相比，第 IV 组的结肠黏膜表现出黏膜愈合和表面上皮再生，恢复了杯状细胞的功能，同时 PCNA、NFkB 和半胱天冬酶-3 的免疫反应性下降。这伴随着纤维化标志物羟脯氨酸和纤维连接蛋白表达的减少。此外，组织抗氧化状态显著改善，组织 MPO 明显减少。与第 III 组相比，胃饥饿素水平显著升高。第 IV 组氧化应激标志物丙二醛、总氧化状态水平显著降低，抗氧化酶超氧化物歧化酶、过氧化氢酶和总细胞总抗氧化能力活性显著增加。
肥胖抑制素的联合治疗抑制了 AA 诱导的结肠炎的发展。数据表明，它通过抗纤维化、抗氧化和抗炎活性具有治疗和保护作用。
