Immunohistochemistry, histopathology, and biomarker studies of swertiamarin, a secoiridoid glycoside, prevents and protects streptozotocin-induced β-cell damage in Wistar rat pancreas
Immunohistochemistry, histopathology, and biomarker studies of swertiamarin, a secoiridoid glycoside, prevents and protects streptozotocin-induced β-cell damage in Wistar rat pancreas
复制标题
DOI：
10.1007/s40618-015-0243-5
复制
发表时间：
2015-06-01
影响因子：
5.4
通讯作者：
Dhanavathy, G.
中科院分区：
文献类型：
--
作者：
Dhanavathy, G.
糖尿病是全球范围内引起stz诱导的糖尿病大鼠代谢综合征的主要原因，导致死亡。口服降糖药治疗糖尿病会产生不良的副作用，因此用天然草药如獐牙菜黄素治疗是有希望的。獐牙菜苦苷是一种从獐牙菜中分离得到的具有抗糖尿病活性的化合物，它能促进β细胞再生，从而逆转糖尿病。目的：(1)利用生物标志物评价獐牙菜黄素对链脲佐菌素诱导的糖尿病大鼠的降糖、降血脂活性。(2)通过免疫组织化学和形态计量学研究，观察獐牙菜黄素处理stz诱导的糖尿病大鼠胰腺、肝脏、肾脏和心脏的组织病理学改变，并证实獐牙菜黄素的细胞保护作用。方法采用链脲佐菌素（STZ 50 mg/kg）腹腔注射诱导雄性Wistar大鼠糖尿病。stz诱导后，高血糖大鼠分别口服15、25、50 mg/kg獐牙菜黄素28 d。格列本脲（2.5 mg/kg）是一种磺胺脲，作为标准药物。通过生化参数测定血糖控制情况。对各脏器进行组织病理学分析，对胰岛进行免疫组化。结果免疫组化结果显示，与stz诱导的糖尿病大鼠相比，口服15、25、50 mg/kg bw的獐牙菜苦苷28 d可显著（p < 0.01）降低空腹血糖、HbA1c、TC、TG、LDL，显著提高血红蛋白、血浆胰岛素、TP、体重和HDL水平（p < 0.01）。研究了獐牙菜黄素对糖代谢酶的影响，发现其具有正常的治疗活性。免疫组织化学研究证实，与stz诱导的糖尿病大鼠相比，獐牙獐牙苋素治疗的糖尿病大鼠胰腺组织病理学研究显示胰岛再生。结论獐牙菜黄素具有降血糖、降血脂、细胞保护和免疫反应等作用，对糖尿病及其他糖尿病相关并发症具有广泛的治疗潜力，可开发为一种有效的口服降糖药物。
Background Diabetes mellitus is globally the major cause for metabolic syndrome in STZ-induced diabetic rats, leading to mortality. Treatment of diabetes by oral hypoglycemic agents causes adverse side effects and thus treatment with natural herbal drugs like swertiamarin is promising. Swertiamarin, an active compound isolated from Enicostemma littorale possesses antidiabetic activity and enhances beta cell regeneration which causes reversal of diabetes.Objectives The present study aims at the following: (1) to evaluate antidiabetic, anti-hyperlipidaemic, activity of swertiamarin in Streptozotocin-induced diabetic rats using biomarkers. (2) To assess histopathological alterations in Pancreas, Liver, Kidney, and Heart of swertiamarin-treated STZ-induced diabetic rats and confirm cytoprotective activity of swertiamarin by Immunohistochemistry and morphometric investigations.Methods Diabetes was induced intraperitoneally in male Wistar rats by Streptozotocin (STZ 50 mg/kg). After STZ-induction, hyperglycemic rats were treated with doses of swertiamarin orally (15, 25, 50 mg/kg) each for 28 days. Glibenclamide (2.5 mg/kg), a sulphonyl urea, was used as a standard drug. The glycemic control was measured by the biochemical parameter assays. Histopathology analysis of organs and immunohistochemistry of islets were carried out.Results Our study results showed that oral administration of swertiamarin at a dosage of 15, 25, 50 mg/kg bw for 28 days resulted in a significant (p < 0.01) decrease in fasting blood glucose, HbA1c, TC, TG, LDL, and increased the levels of hemoglobin, plasma insulin, TP, body weight, and HDL levels significantly (p < 0.01) when compared to STZ-induced diabetic rats, as confirmed by immunohistochemical studies. The effect of swertiamarin on Carbohydrate-metabolizing enzymes was investigated and found to have normal therapeutic activity. Histopathological studies of Pancreas of swertiamarin-treated diabetic rats showed regeneration of islets when compared to STZ-induced diabetic rats, as confirmed by immunohistochemical studies.Conclusion Our research results clearly substantiate that swertiamarin possesses antihyperglycemic, antihyperlipidemic, cytoprotective, and immune reactivity and also a broad spectrum potential of treating diabetes and other complications related to diabetes and hence can be developed into a potent oral antidiabetic drug.