Department of Pharmacology, Faculty of Medicine, Minia University, 61111 Minia, Egypt.
Department of Pharmacology, Faculty of Medicine, Minia University, 61111 Minia, Egypt; Department of Basic Medical Sciences, College of Medicine, Prince Sattam Bin Abdulaziz University, Al Kharj, Saudia Arabia.
Eur J Pharmacol. 2018 Jun 15;829:63-69. doi: 10.1016/j.ejphar.2018.04.005. Epub 2018 Apr 12.
Ischemic heart disease is a common cause of mortality worldwide. Sitagliptin is a new anti-diabetic drug acting as dipeptidyl peptidase-4 (DPP-4) inhibitor. The study investigated the ability of sitagliptin to prevent pathological changes of isoproterenol- (ISO-) induced myocardial injury in rats. The role of nitric oxide (NO) was also reported. Rats were assorted into six groups (n = 7) and treated for 12 days. Group 1: normal control, received normal saline. Group 2, sitagliptin control, received sitagliptin (10 mg/kg, orally). Group 3, ISO group, received isoproterenol (ISO) (100 mg/kg, i.p.). Group 4, sitagliptin + ISO, co-treated with sitagliptin plus ISO. Group 5, L-NNA + ISO, co-treated with L-N-nitro arginine (L-NNA) (25 mg/kg, orally) plus ISO. Group 6, sitagliptin + L-NNA + ISO, co-treated with sitagliptin plus ISO plus L-NNA. Blood glucose, serum creatine kinase-MB (CK-MB, and cardiac tissue parameters of oxidative stress parameters and NO, along with histopathological examination, and immunohistochemical study of inducible NO synthase (iNOS) expression were done. The results showed that sitagliptin caused a significant reduction in CK-MB, and attenuated histopathological damage-induced by ISO. Its effect was associated with a significant decrease in oxidative stress parameters, NO contents as well as by a significant decrease in the expression of iNOS in cardiac tissue. The protective effect of sitagliptin was abrogated by coadministartion of L-NNA, a selective inhibitor of both endothelial NOS (eNOS) and neuronal NOS (nNOS). In conclusion, sitagliptin ameliorates ISO-induced myocardial injury via antioxidant effects and modulation of NOS enzymes.
缺血性心脏病是全球范围内常见的死亡原因。西他列汀是一种新型的抗糖尿病药物，作为二肽基肽酶-4（DPP-4）抑制剂。本研究旨在探讨西他列汀预防异丙肾上腺素（ISO）诱导的大鼠心肌损伤的病理变化的能力，并报告了一氧化氮（NO）的作用。将大鼠分为六组（n=7），并治疗 12 天。第 1 组：正常对照组，给予生理盐水。第 2 组，西他列汀对照组，给予西他列汀（10mg/kg，口服）。第 3 组，ISO 组，给予异丙肾上腺素（ISO）（100mg/kg，ip）。第 4 组，西他列汀+ISO，用西他列汀加 ISO 共同处理。第 5 组，L-NNA+ISO，用 L-N-硝基精氨酸（L-NNA）（25mg/kg，口服）加 ISO 共同处理。第 6 组，西他列汀+L-NNA+ISO，用西他列汀加 ISO 加 L-NNA 共同处理。进行血糖、血清肌酸激酶-MB（CK-MB）和心脏组织氧化应激参数及 NO 的测定，并进行组织病理学检查和诱导型一氧化氮合酶（iNOS）表达的免疫组织化学研究。结果表明，西他列汀显著降低 CK-MB，并减轻 ISO 诱导的组织病理学损伤。其作用与氧化应激参数、NO 含量的显著降低以及心脏组织中 iNOS 表达的显著降低有关。L-NNA 的共同给药（一种内皮型一氧化氮合酶（eNOS）和神经元型一氧化氮合酶（nNOS）的选择性抑制剂）可阻断西他列汀的保护作用。结论：西他列汀通过抗氧化作用和调节 NOS 酶改善 ISO 诱导的心肌损伤。
