Young Researchers and Elite Club, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
Department of Anatomical Sciences & Cognitive Neuroscience, Faculty of Medicine, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
CNS Neurol Disord Drug Targets. 2021;20(1):76-86. doi: 10.2174/1871527319666200922160627.
Atorvastatin is a member of statins, which has shown positive vascular effects, anti-oxidant, anti-platelet, and anti-apoptotic properties.
In this study, we hypothesized that atorvastatin could prevent the neurons lost in the hippocampal dentate gyrus region after transient global Ischemia/Reperfusion (I/R) through its anti- oxidant and anti-apoptotic activities.
Twenty-four male Wistar rats, 12-13 weeks old and weighing 250-300 g, were divided randomly into four groups: control, I/R, vehicle (I/R treated with NaCl) and experiment (I/R treated with atorvastatin, 10 mg/kg); rats were sacrificed 96 hours after I/R. Quantitative expression of genes (caspase 8, p53, bax, bcl2, cytochrome c) was studied. The MDA level, SOD, CAT, and GPx activities were measured with biochemical tests. To detect apoptotic cells, TUNEL and Nissl staining were performed. Mitochondria were prepared from the hippocampus rats and used for the quantification of mitochondrial ROS, ATP level, GSH content, membrane potential, cytochrome c release, and determination of mitochondrial swelling.
Atorvastatin attenuated the overexpression of bax, cytochrome C, p53, and caspase8 mRNAs and induced expression of bcl-2 mRNA (P<0.001). Atorvastatin treatment increased anti-oxidant enzyme levels (P<0.01). Treatment with atorvastatin reduced the number of TUNEL-positive cells. It could decrease the cytochrome c release (P<0.01), inhibit the decrease of MMP (P<0.001) and increase the ATP level (P<0.001) in hippocampal mitochondria compared with the I/R group.
Atorvastatin treatment in I/R rats decreases oxidative stress, production of ROS, apoptosis rate in neuronal cells, and improves the mitochondrial function. Hence, atorvastatin has a proper neuronal protective effect against the I/R injury in the brain.
阿托伐他汀是他汀类药物的一种，具有积极的血管作用、抗氧化、抗血小板和抗细胞凋亡特性。
本研究假设阿托伐他汀通过其抗氧化和抗细胞凋亡作用，可以防止短暂全脑缺血/再灌注（I/R）后海马齿状回区域的神经元丢失。
将 24 只雄性 Wistar 大鼠，12-13 周龄，体重 250-300g，随机分为 4 组：对照组、I/R 组、载体组（I/R 用 NaCl 处理）和实验组（I/R 用阿托伐他汀 10mg/kg 处理）；I/R 后 96 小时处死大鼠。研究基因（半胱天冬酶 8、p53、bax、bcl2、细胞色素 c）的定量表达。用生化试验测定 MDA 水平、SOD、CAT 和 GPx 活性。通过 TUNEL 和尼氏染色检测凋亡细胞。从大鼠海马制备线粒体，用于定量测定线粒体 ROS、ATP 水平、GSH 含量、膜电位、细胞色素 c 释放以及线粒体肿胀的测定。
阿托伐他汀减弱了 bax、细胞色素 C、p53 和 caspase8mRNA 的过度表达，并诱导了 bcl-2mRNA 的表达（P<0.001）。阿托伐他汀治疗增加了抗氧化酶水平（P<0.01）。阿托伐他汀治疗减少了 TUNEL 阳性细胞的数量。它可以减少细胞色素 c 的释放（P<0.01），抑制 MMP 的降低（P<0.001），并增加海马线粒体中的 ATP 水平（P<0.001）与 I/R 组相比。
阿托伐他汀治疗 I/R 大鼠可降低氧化应激、ROS 产生、神经元细胞凋亡率，并改善线粒体功能。因此，阿托伐他汀对脑 I/R 损伤具有适当的神经保护作用。
