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节节草提取物包裹金纳米粒子对氧葡萄糖剥夺/复氧诱导的神经保护作用。

Neuroprotective effect of Dictyopteris divaricata extract-capped gold nanoparticles against oxygen and glucose deprivation/reoxygenation.

机构信息

Bio-IT Fusion Technology Research Institute, Pusan National University, Busan 46241, Republic of Korea.

Biomedical Research Institute, Pusan National University Hospital, Busan 49241, Republic of Korea.

出版信息

Colloids Surf B Biointerfaces. 2019 Jul 1;179:421-428. doi: 10.1016/j.colsurfb.2019.03.066. Epub 2019 Mar 29.

DOI:10.1016/j.colsurfb.2019.03.066
PMID:31003168
Abstract

Combination therapy remains a promising approach to ameliorate cerebral ischemia injury. Nevertheless, the primary mechanism of the neuroprotective properties of Dictyopteris divaricata extract-capped gold nanoparticles (DD-GNPs) is not completely understood. DD-GNPs displayed maximum absorption at 525 nm and a diameter of 62.6 ± 1.2 nm, with a zeta potential value of -26.1 ± 0.6 mV. High resolution-transmission electron microscopy confirmed the spherical shape and average diameter (28.01 ± 2.03 nm). Crystalline structure and gold nanoparticle synthesis of DD-GNPs were determined by X-ray powder diffraction, and the presence of elemental gold was confirmed by energy-dispersive X-ray spectroscopy and Fourier transform-infrared spectroscopy. We examined the neuroprotective properties of DD-GNPs and explored their potential mechanisms in human SH-SY5Y neuroblastoma cells treated with oxygen and glucose deprivation/reoxygenation (OGD/R). We found that DD-GNPs inhibited OGD/R-induced release of lactate dehydrogenase (LDH), loss of cell viability, and production of reactive oxygen species. This neuroprotection was accompanied by regulation of apoptosis-related proteins, as indicated by decreased levels of cleaved-caspase-3, cleaved-PARP, cleaved-caspase-9, p53, p21, and Bax, as well as an increased level of Bcl-2. Notably, the neuroprotective effects of DD-GNPs were partially abolished by HO-1, NQO1, Nrf2, and AMPK knockdown. Our results established that DD-GNPs effectively attenuated OGD/R-stimulated neuronal injury, as evidenced by reduced neuronal injury. Even though the accumulating evidence has indicated the low toxicity and minimal side effects of GNPs, experimental clinical trials of DD-GNPs are still limited because of the lack of knowledge regarding the effects of DD-GNPs as neuroprotective agents against neurodegenerative diseases.

摘要

联合治疗仍然是改善脑缺血损伤的一种有前途的方法。然而,裂叶海金沙提取物包裹金纳米粒子(DD-GNPs)的神经保护特性的主要机制尚不完全清楚。DD-GNPs 在 525nm 处显示最大吸收,直径为 62.6±1.2nm,zeta 电位值为-26.1±0.6mV。高分辨率透射电子显微镜证实了球形和平均直径(28.01±2.03nm)。X 射线粉末衍射确定了 DD-GNPs 的晶体结构和金纳米粒子合成,通过能量色散 X 射线光谱和傅里叶变换-红外光谱证实了元素金的存在。我们研究了 DD-GNPs 的神经保护特性,并在人 SH-SY5Y 神经母细胞瘤细胞中探讨了它们在氧和葡萄糖剥夺/再氧合(OGD/R)中的潜在机制。我们发现 DD-GNPs 抑制了 OGD/R 诱导的乳酸脱氢酶(LDH)释放、细胞活力丧失和活性氧的产生。这种神经保护作用伴随着凋亡相关蛋白的调节,表现为 cleaved-caspase-3、cleaved-PARP、cleaved-caspase-9、p53、p21 和 Bax 的水平降低,以及 Bcl-2 的水平升高。值得注意的是,HO-1、NQO1、Nrf2 和 AMPK 敲低部分消除了 DD-GNPs 的神经保护作用。我们的结果表明,DD-GNPs 有效减轻了 OGD/R 刺激的神经元损伤,这表现在神经元损伤减少。尽管越来越多的证据表明 GNPs 的低毒性和最小的副作用,但由于缺乏关于 DD-GNPs 作为神经保护剂对抗神经退行性疾病的作用的知识,DD-GNPs 的实验临床试验仍然有限。

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