Department of Clinical Laboratory Sciences, College of Pharmacy, University of Al-Qadisiyah, Diwaniya, Iraq.
Department of Pharmacology and Therapeutics, College of Medicine, University of Al-Qadisiyah, Diwaniya, Iraq.
J Med Life. 2023 Mar;16(3):451-457. doi: 10.25122/jml-2022-0298.
Atherosclerosis is a common and serious vascular disease that underlies many cardiovascular and cerebrovascular illnesses, including heart attack and stroke. Atherosclerosis-related illnesses have increased in prevalence and now pose a substantial burden on individuals and society. Autophagy (AP) is a process in which cytoplasmic components are engulfed by a double-membrane structure, such as defective organelles and aged, damaged, and flawed proteins. Autophagy is essential for maintaining a proper cellular equilibrium and plays a vital homeostatic role in physiological settings by liberating nutrients from macromolecules and removing undesirable cellular components. This study aimed to investigate the effect of Sitagliptin on the progression of atherosclerosis. Twenty-one male New Zealand White rabbits weighing 2-2.5 kg each were split into three groups: normal control, atherogenic control, and Sitagliptin-treated. The following parameters: serum triglycerides (TG), total cholesterol (TC), LDL, and a tissue autophagy marker (p62) using ELISA, aortic mRNA expression of mTORC1 marker using Real-Time Quantitative PCR(RT-qPCR), and histological inspection of the aorta were assessed. The mRNA expression of mTORC1 and the lipid profile of aortic tissue are considerably elevated in atherogenic diet-fed animals. Histopathological analysis confirmed the presence of a substantial atherosclerotic lesion in the animals fed an atherogenic diet. However, compared to an atherogenic control group, Sitagliptin dramatically reduced lipid profile, P62 aortic level, and mRNA expression of mTORC1. Sitagliptin medication slowed the development of atherosclerosis via increasing autophagy through suppression of the mTORC1 signaling pathway.
动脉粥样硬化是一种常见且严重的血管疾病，是许多心血管和脑血管疾病的基础，包括心脏病发作和中风。与动脉粥样硬化相关的疾病患病率有所增加，现在给个人和社会带来了巨大的负担。自噬（AP）是一种细胞质成分被双层膜结构包裹的过程，如受损的细胞器和衰老、受损和有缺陷的蛋白质。自噬对于维持适当的细胞平衡至关重要，它在生理环境中通过从大分子中释放营养物质和清除不需要的细胞成分来发挥重要的动态平衡作用。本研究旨在探讨西他列汀对动脉粥样硬化进展的影响。将 21 只体重为 2-2.5 公斤的雄性新西兰白兔分为三组：正常对照组、动脉粥样硬化对照组和西他列汀治疗组。采用 ELISA 法检测血清甘油三酯（TG）、总胆固醇（TC）、LDL 和组织自噬标志物（p62），采用实时定量 PCR（RT-qPCR）检测主动脉 mTORC1 标志物的 mRNA 表达，以及主动脉的组织学检查。动脉粥样硬化饮食喂养的动物的 mTORC1 标志物的 mRNA 表达和主动脉组织的脂质谱显著升高。组织病理学分析证实，给予动脉粥样硬化饮食的动物存在大量动脉粥样硬化病变。然而，与动脉粥样硬化对照组相比，西他列汀显著降低了脂质谱、p62 主动脉水平和 mTORC1 的 mRNA 表达。西他列汀通过抑制 mTORC1 信号通路增加自噬，从而减缓动脉粥样硬化的发展。
