Biochemistry Department, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt.
Biochemistry Division, Chemistry Department, Faculty of Science, Zagazig University, Zagazig, Egypt.
Arch Physiol Biochem. 2022 Dec;128(6):1611-1618. doi: 10.1080/13813455.2020.1786129. Epub 2020 Jul 2.
Our study aimed to illustrate the effect of the antihistaminic drug azelastine on aortic calcification in diabetic hyperlipidemic (DH) rats along with the underlying molecular mechanism.
Twenty-four male albino Wistar rats were categorised into four groups. One group received normal rodent chow (normal group), while the other groups were rendered diabetic and hyperlipidemic; one received no drugs and served as a positive control while the other two groups received either azelastine (4 mg/kg) or 10-dehydrogingerdione (10 mg/kg) orally and daily for 8 weeks.
Azelastine significantly reduced blood glucose, HbA1c and serum ALP, OCN, downregulated apo B, improved the lipid profile (LDL-c decrease and HDL-c increase), attenuated calcium deposition and aortic calcification as compared to control group. 10-DHGD showed comparatively lower effect.
Anti-calcifying effect of azelastine might be related to upregulation of apo A (HDL-c) and downregulation of apo B mRNA expression indeed good modulator of aortic calcification.
Many studies have indicated that high-density lipoprotein-cholesterol (HDL-c) is inversely correlated with atherosclerotic plaque progression and could reduce cardiovascular disease risk. An anti-calcifying effect of HDL-c has been reported and targeting this lipoprotein may therefore be a valuable approach to vascular calcification control. Azelastine is a selective H1 antagonist that was identified to increase mRNA expression of apolipoprotein A. This encouraged us to investigate the effect of azelastine on lipid profile and markers of aortic calcification in DH rats. Our findings showed that azelastine ameliorated aortic calcification and increased apoA expression along with a decline in apo B. This may represent the underlying mechanism while the histopathological findings offered a significant support to the collected biochemical data.
本研究旨在阐述抗组胺药氮卓斯汀对糖尿病高脂血症（DH）大鼠主动脉钙化的影响及其潜在的分子机制。
将 24 只雄性白化 Wistar 大鼠分为 4 组。一组给予普通啮齿动物饲料（正常组），其余三组制作成糖尿病高脂血症模型；一组未给予药物作为阳性对照，另两组分别给予氮卓斯汀（4mg/kg）或 10-去氢姜二酮（10mg/kg）口服，每天一次，共 8 周。
氮卓斯汀显著降低血糖、HbA1c 和血清碱性磷酸酶、骨钙素，下调载脂蛋白 B，改善血脂谱（降低 LDL-c，增加 HDL-c），与对照组相比，减轻钙沉积和主动脉钙化。10-DHGD 表现出相对较低的效果。
氮卓斯汀的抗钙化作用可能与载脂蛋白 A（HDL-c）的上调和载脂蛋白 B mRNA 表达的下调有关，确实是主动脉钙化的良好调节剂。
许多研究表明，高密度脂蛋白胆固醇（HDL-c）与动脉粥样硬化斑块进展呈负相关，可降低心血管疾病风险。已经报道了 HDL-c 的抗钙化作用，因此靶向这种脂蛋白可能是控制血管钙化的一种有价值的方法。氮卓斯汀是一种选择性 H1 拮抗剂，被鉴定为增加载脂蛋白 A 的 mRNA 表达。这鼓励我们研究氮卓斯汀对 DH 大鼠血脂谱和主动脉钙化标志物的影响。我们的研究结果表明，氮卓斯汀改善了主动脉钙化，增加了载脂蛋白 A 的表达，同时降低了载脂蛋白 B。这可能代表了潜在的机制，而组织病理学发现为收集的生化数据提供了重要支持。
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