Department of Pharmacology, Toxicology and Clinical Pharmacology, Iuliu Haţieganu University of Medicine and Pharmacy Cluj-Napoca, Gheorghe Marinescu Street, No. 23, 400337 Cluj-Napoca, Romania.
Department of Medical Informatics and Biostatistics, Iuliu Haţieganu University of Medicine and Pharmacy Cluj-Napoca, Louis Pasteur Street, No. 6, 400349 Cluj-Napoca, Romania.
Int J Mol Sci. 2022 Jan 27;23(3):1438. doi: 10.3390/ijms23031438.
The present study aims to compare the oxidative stress biomarkers, pro-inflammatory cytokines, and histological changes induced by three cardiovascular risk factors, namely, hypertension, dyslipidemia, and type 1 diabetes mellitus. Hypertension was induced with 40 mg/kg body weight (b.w.) of N omega-nitro-L-arginine-methyl (L-NAME) administered orally. Dyslipidemia was induced by the administration of a diet with a high cholesterol (2%) content. Diabetes mellitus was induced by intraperitoneal administration of a single dose of streptozocin (65 mg/kg). Malondialdehyde (MDA) and total oxidative status (TOS) are increased by all three cardiovascular risk factors (up to 207%). The indirect assessment of NO synthesis (NOx) is observed to be reduced after L-NAME administration (43%), and dyslipidemia induction (16%), while type 1 diabetes mellitus is associated with the highest levels of NOx (increased 112%). Hypertension, dyslipidemia, and type 1 diabetes reduced the total antioxidative capacity (TAC) and total thiol (SH) levels (up to 57%). The values of evaluated pro-inflammatory cytokines, tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β), assessed from the ascending aorta were elevated by all three cardiovascular risk factors, with the highest levels induced by type 1 diabetes mellitus (up to 259%). The histopathological examination of the ascending and descending aorta revealed reversible pro-atherogenic changes consisting of the accumulation of lipid droplets in the subendothelial connective tissue on rats with hypertension and dyslipidemia. Irreversible pro-atherogenic changes consisting of a reduction of the specific elasticity of the arteries were observed in rats with type 1 diabetes mellitus. Type 1 diabetes mellitus demonstrates an alteration of the oxidative stress parameters, the elevation of tissue levels of the pro-inflammatory cytokines and causing irreversible pro-atherogenic changes on the aortic wall.
本研究旨在比较三种心血管风险因素(高血压、血脂异常和 1 型糖尿病)引起的氧化应激生物标志物、促炎细胞因子和组织学变化。高血压通过口服给予 40mg/kg 体重(b.w.)的 N omega-硝基-L-精氨酸甲酯(L-NAME)诱导。高脂血症通过给予高胆固醇(2%)饮食诱导。1 型糖尿病通过腹腔内给予链脲佐菌素(65mg/kg)单次注射诱导。丙二醛(MDA)和总氧化状态(TOS)在所有三种心血管风险因素下均升高(高达 207%)。L-NAME 给药后(43%)和血脂异常诱导后(16%)间接评估的 NO 合成(NOx)观察到减少,而 1 型糖尿病与最高水平的 NOx 相关(增加 112%)。高血压、血脂异常和 1 型糖尿病降低了总抗氧化能力(TAC)和总巯基(SH)水平(高达 57%)。从升主动脉评估的评价促炎细胞因子肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)和白细胞介素-1β(IL-1β)的水平,被所有三种心血管风险因素升高,其中 1 型糖尿病诱导的水平最高(高达 259%)。升主动脉和降主动脉的组织病理学检查显示,高血压和血脂异常大鼠的动脉内皮下结缔组织中脂质滴的积累存在可逆的促动脉粥样硬化变化。在 1 型糖尿病大鼠中观察到不可逆的促动脉粥样硬化变化,表现为动脉特定弹性的降低。1 型糖尿病改变了氧化应激参数,升高了组织中促炎细胞因子的水平,并导致主动脉壁发生不可逆的促动脉粥样硬化变化。