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罗米地辛和二甲双胍纳米材料联合链脲佐菌素递药用于治疗动物模型的阿尔茨海默病。

Romidepsin and metformin nanomaterials delivery on streptozocin for the treatment of Alzheimer's disease in animal model.

机构信息

Department of Neurology, the Second Affiliated Hospital of Nanchang University, Nanchang 330006, China.

Department of Neurology, the Second Affiliated Hospital of Nanchang University, Nanchang 330006, China.

出版信息

Biomed Pharmacother. 2021 Sep;141:111864. doi: 10.1016/j.biopha.2021.111864. Epub 2021 Jul 14.

Abstract

Brain insulin signal anomalies are implicated in Alzheimer's disease (AD) pathology. In this background, metformin, an insulin sensitizer's neuroprotective effectiveness, has been established in the prior findings. In the present investigation, combining an epigenetic modulator, romidepsin, and metformin will improve the gene expressions of neurotrophic factors and reduce AD-associated biochemical and cellular changes by loading them mainly into a nanocarrier surface-modified framework for improved therapeutic effectiveness and bioavailability. In the present investigation, the mediated intra-cerebroventricular streptozocin (3 mg/kg) AD of the model was loaded with metformin and romidepsin into a poloxamer stabilized polymer nanocarrier system. Free combination drug therapy (Romidepsin 25 mg/kg and metformin 5 mg/kg) reduced biochemical and cellular variations over three weeks, respectively, compared to either free treatment (Romidepsin 50 mg/kg and metformin 10 mg/kg). The nanoformulations (Romidepsin 25 mg/kg and Metformin 5 mg/kg), as shown by enhanced significantly reduce stress and high neurotrophic factors, has also exerted superior neurological effectiveness than the free combination of drugs. Eventually, through the Poloxamer stable polymeric nanocarrier framework, the synergistic neuroprotective efficacy of metformin and romidepsin has improved.

摘要

脑胰岛素信号异常与阿尔茨海默病(AD)的病理有关。在此背景下,先前的研究已经证实了胰岛素增敏剂二甲双胍的神经保护作用。在本研究中,将一种表观遗传调节剂罗米地辛与二甲双胍联合使用,通过将它们主要加载到纳米载体表面修饰的框架中,以提高治疗效果和生物利用度,从而改善神经营养因子的基因表达,并减少 AD 相关的生化和细胞变化。在本研究中,通过立体定位脑室内注射链脲佐菌素(3 mg/kg)构建 AD 模型,将二甲双胍和罗米地辛加载到泊洛沙姆稳定的聚合物纳米载体系统中。与单独给药(罗米地辛 50 mg/kg 和二甲双胍 10 mg/kg)相比,联合药物治疗(罗米地辛 25 mg/kg 和二甲双胍 5 mg/kg)在 3 周内分别降低了生化和细胞变化。纳米制剂(罗米地辛 25 mg/kg 和二甲双胍 5 mg/kg)通过增强显著降低应激和高神经营养因子,也表现出优于药物联合的神经学效果。最终,通过泊洛沙姆稳定的聚合物纳米载体框架,提高了二甲双胍和罗米地辛的协同神经保护作用。

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