目的:本研究旨在比较β-谷甾醇纳米粒(BETN)和β-谷甾醇(BET)对认知功能障碍的影响,氧化应激,使用计算机模拟和体内方法在心肌梗塞(MI)大鼠模型中的炎症。
方法:使用AutodockVina进行对接,使用Gromacs进行动力学模拟,评估β-谷甾醇(BET)和髓过氧化物酶(MPO)配体-受体结合亲和力。BET纳米颗粒,通过溶剂蒸发制备,通过纳米粒子分析仪确认了它们的大小。通过Morris水迷宫和Cook爬杆试验评估ISO诱导的大鼠认知障碍。氧化应激,炎症,通过测量GSH来评估心脏损伤,SOD,MDA,MPO,CkMB,LDH,脂质分布,和ECGs。使用H&E染色进行CA1海马和心肌组织的组织病理学。
结果:计算机模拟分析显示BET和MPO之间有很强的结合亲和力,提示BET的潜在抗炎作用。BETN(119.6±42.6nm;PDI:0.809)显著改善MI诱导的大鼠认知功能障碍(p<0.001***),海马GSH(p<0.01**)和SOD(p<0.01**)水平升高,海马MDA(p<0.05*)和MPO(p<0.01**)水平降低。BETN还升高了心脏GSH(p<0.01**)和SOD(p<0.01**)水平,并降低了心脏MPO(p<0.01**),CkMB(p<0.001**)和LDH(p<0.001**)水平。它恢复了脂质分布,归一化的ECG模式,改善海马CA1区和心肌的组织学。
结论:与BET治疗相比,BETN在改善认知障碍方面更有效,氧化损伤,和MI大鼠的炎症,提示其治疗MI认知功能障碍和相关病理变化的潜力。
OBJECTIVE: This study aimed to compare the effects of β-sitosterol nanoparticles (BETNs) and β-sitosterol (BET) on cognitive impairment, oxidative stress, and inflammation in a myocardial infarction (MI) rat model using in silico and in vivo methods.
METHODS: β-Sitosterol (BET) and
myeloperoxidase (MPO) ligand-receptor binding affinities were evaluated using Autodock Vina for docking and Gromacs for dynamics simulations. BET nanoparticles, prepared via solvent evaporation, had their size confirmed by a nanoparticle analyzer. ISO-induced cognitive impairment in rats was assessed through Morris water maze and Cook\'s pole climbing tests. Oxidative stress, inflammation, and cardiac injury were evaluated by measuring GSH, SOD, MDA, MPO, CkMB, LDH, lipid profiles, and ECGs. Histopathology of the CA1 hippocampus and myocardial tissue was performed using H&E staining.
RESULTS: In silico analyses revealed strong binding affinities between BET and MPO, suggesting BET\'s potential anti-inflammatory effect. BETN (119.6 ± 42.6 nm; PDI: 0.809) significantly improved MI-induced cognitive dysfunction in rats (p < 0.001 ***), increased hippocampal GSH (p < 0.01 **) and SOD (p < 0.01 **) levels, and decreased hippocampal MDA (p < 0.05 *) and MPO levels (p < 0.01 **). BETNs also elevated cardiac GSH (p < 0.01 **) and SOD (p < 0.01 **) levels and reduced cardiac MPO (p < 0.01 **), CkMB (p < 0.001 **) and LDH (p < 0.001 **) levels. It restored lipid profiles, normalized ECG patterns, and improved histology in the hippocampal CA1 region and myocardium.
CONCLUSIONS: Compared with BET treatment, BETNs were more effective in improving cognitive impairment, oxidative damage, and inflammation in MI rats, suggesting its potential in treating cognitive dysfunction and associated pathological changes in MI.