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西他列汀和芦丁联合给药可改善链脲佐菌素诱导的糖尿病白化大鼠的肝损伤:α 平滑肌肌动蛋白作用概述。

Concomitant administration of sitagliptin and rutin improves the adverse hepatic alterations in streptozotocin-induced diabetes mellitus in albino rats: an overview of the role of alpha smooth muscle actin.

机构信息

Department of Anatomy and Embryology, Faculty of Medicine, Cairo University, Cairo, Egypt.

出版信息

Folia Morphol (Warsz). 2021;80(4):870-880. doi: 10.5603/FM.a2020.0130. Epub 2020 Oct 30.

DOI:10.5603/FM.a2020.0130
PMID:33124035
Abstract

BACKGROUND

Diabetes mellitus (DM), one of the commonest worldwide metabolic conditions, is believed to be associated with an imbalance between oxidants and antioxidants. Sitagliptin is an oral anti-hyperglycaemic drug that blocks dipeptidyl peptidase 4 (DPP4). Rutin is a polyphenolic natural flavonoid which has antioxidant and anti-proliferative activity. The aim of the present work is to elucidate the concomitant effect of sitagliptin and rutin on the deleterious alterations in the liver of experimentally induced diabetes in rats.

MATERIALS AND METHODS

Fifty adult male albino rats, weighing 170-200 g were used. Rats were randomly divided into five groups (n = 10): group 1 (control group), the other four groups (groups II, III, IV and V) received a single i.p. injection of streptozotocin, 65 mg/kg body weight to induce diabetes; group II (diabetic), group III (diabetic and rutin administered), group IV (diabetic and sitagliptin administered), and group V (diabetic with sitagliptin and rutin concomitantly administered). Haematoxylin and eosin, Masson trichrome, periodic acid Schiff, immune-histochemistry: a-smooth muscle actin (a-SMA), histomorphometric analysis, liver enzymes and oxidants/anti-oxidants; malondialdehyde/glutathione and were done.

RESULTS

Distorted hepatic architecture, dilatation, congestion of sinusoids and central veins as well as cytoplasmic vacuolations were remarkable changes in the diabetic group. There was extravasation of blood, diffuse fibrous tissue formation, increase in the mean values of liver enzymes, oxidative markers and a-SMA expression in the same group. The aforementioned changes were ameliorated in groups III and IV. Concomitant administration of sitagliptin and rutin resulted in marked enhancement of these hepatic alterations.

CONCLUSIONS

Combination of sitagliptin and rutin has an ameliorating effect on the hepatic deterioration induced by diabetes, which is better than either sitagliptin or rutin alone.

摘要

背景

糖尿病(DM)是全球最常见的代谢性疾病之一,据信与氧化剂和抗氧化剂之间的失衡有关。西他列汀是一种口服抗高血糖药物,可阻断二肽基肽酶 4(DPP4)。芦丁是一种多酚类天然类黄酮,具有抗氧化和抗增殖活性。本工作旨在阐明西他列汀和芦丁对实验性诱导糖尿病大鼠肝脏有害改变的协同作用。

材料和方法

使用 50 只成年雄性白化大鼠,体重 170-200g。大鼠随机分为五组(n=10):第 1 组(对照组),其余四组(第 2、3、4 和 5 组)单次腹腔注射链脲佐菌素,65mg/kg 体重诱导糖尿病;第 2 组(糖尿病),第 3 组(糖尿病和芦丁给药),第 4 组(糖尿病和西他列汀给药),第 5 组(糖尿病与西他列汀和芦丁同时给药)。苏木精和伊红、马松三色、过碘酸希夫、免疫组织化学:α-平滑肌肌动蛋白(α-SMA)、组织形态计量分析、肝酶和氧化剂/抗氧化剂;丙二醛/谷胱甘肽进行了分析。

结果

肝组织结构扭曲、扩张、窦状隙和中央静脉充血以及细胞质空泡化是糖尿病组的显著变化。同一组有血液外渗、弥漫性纤维组织形成、肝酶、氧化标志物和α-SMA 表达的平均值增加。在第 3 组和第 4 组中,这些变化得到了改善。西他列汀和芦丁联合给药显著增强了这些肝改变。

结论

西他列汀和芦丁联合使用对糖尿病引起的肝恶化有改善作用,优于单独使用西他列汀或芦丁。

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