Şen Selçuk, Hacıosmanoğlu Ebru
Department of Medical Pharmacology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, TUR.
Department of Biophysics, Faculty of Medicine, Bezmialem Vakif University, Istanbul, TUR.
Cureus. 2022 Jul 29;14(7):e27429. doi: 10.7759/cureus.27429. eCollection 2022 Jul.
The effect of antihypertensive drugs, especially drugs modulating the renin-angiotensin-aldosterone-system (RAAS), on neurodegenerative diseases still needs to be investigated. This study aimed to compare the effects of three different antihypertensive drugs (telmisartan, perindopril, and nebivolol) on neuroprotection and acetylcholine (ACh) levels against lipopolysaccharide (LPS)-induced injury in a differentiated SH-SY5Y cell line. Cells were treated with retinoic acid for differentiation to a neuronal phenotype. LPS 20 (μg/mL) was applied to the cells for one hour. Then, the cells were treated with 1, 5, and 10 µg/mL concentrations of telmisartan, perindopril, and nebivolol separately for 24 hours, except for the control and LPS alone groups. Cell viability was evaluated using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. ACh levels were analyzed using an enzyme immunosorbent assay in the culture medium. Tumor necrosis factor-alpha (TNF-α), interleukin 1 beta (IL-1β), and nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) expressions were evaluated using western blot analysis. Telmisartan demonstrated the highest cell viability against LPS-induced injury, whereas the protective effect of perindopril was moderate. Nebivolol showed no neuroprotective effect. The protective effect of 10-µg/mL telmisartan was superior to 10 µg/mL perindopril (p=0.006), 5 µg/mL perindopril (p=0.001), 1 µg/mL perindopril (p=0.001), and 1, 5, and 10 µg/mL nebivolol (p<0.001). Among all the study drugs, only telmisartan provided a statistically significant increase in ACh levels after LPS-induced injury. Additionally, the administration of telmisartan provided a concentration-dependent reduction in TNF-α, IL-1β, and NFκB expression against LPS-induced neuroinflammation. These findings suggest that telmisartan has a superior neuroprotective effect against LPS-induced injury in neuron-like cells compared with both perindopril and nebivolol.
抗高血压药物，尤其是调节肾素-血管紧张素-醛固酮系统（RAAS）的药物，对神经退行性疾病的影响仍有待研究。本研究旨在比较三种不同抗高血压药物（替米沙坦、培哚普利和奈必洛尔）对分化的SH-SY5Y细胞系中脂多糖（LPS）诱导损伤的神经保护作用及乙酰胆碱（ACh）水平的影响。用视黄酸处理细胞使其分化为神经元表型。将20μg/mL的LPS作用于细胞1小时。然后，除对照组和单独使用LPS组外，分别用1、5和10μg/mL浓度的替米沙坦、培哚普利和奈必洛尔处理细胞24小时。使用3-（4,5-二甲基噻唑-2-基）-2,5-二苯基四氮唑溴盐（MTT）法评估细胞活力。在培养基中使用酶联免疫吸附测定法分析ACh水平。使用蛋白质免疫印迹分析评估肿瘤坏死因子-α（TNF-α）、白细胞介素1β（IL-1β）和活化B细胞核因子κB（NFκB）的表达。替米沙坦对LPS诱导的损伤表现出最高的细胞活力，而培哚普利的保护作用中等。奈必洛尔未显示出神经保护作用。10μg/mL替米沙坦的保护作用优于10μg/mL培哚普利（p = 0.006）、5μg/mL培哚普利（p = 0.001）、1μg/mL培哚普利（p = 0.001）以及1、5和10μg/mL奈必洛尔（p < 0.001）。在所有研究药物中，只有替米沙坦在LPS诱导损伤后使ACh水平有统计学意义的升高。此外，替米沙坦的给药对LPS诱导的神经炎症使TNF-α、IL-1β和NFκB表达呈浓度依赖性降低。这些发现表明，与培哚普利和奈必洛尔相比，替米沙坦对神经元样细胞中LPS诱导的损伤具有更好的神经保护作用。
