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Nrf2-抗氧化剂在 根提取物的放射防护中的作用。

Role of Nrf2-antioxidant in radioprotection by root extract of .

机构信息

a Division of Capacity Enhancement and Product Induction, Institute of Nuclear Medicine and Allied Sciences, Defence Research and Development Organization , Delhi , India.

出版信息

Int J Radiat Biol. 2019 Aug;95(8):1122-1134. doi: 10.1080/09553002.2019.1607607. Epub 2019 Apr 30.

DOI:10.1080/09553002.2019.1607607
PMID:30998083
Abstract

, a Trans-Himalayan plant is an important medicinal herb. In this study, the radio-modulatory efficacy of aqueous root extract of was investigated. Normal Kidney Epithelium cells were treated with extract (50-200 g/ml) and exposed to 3 Gy of γ-radiation, while C57BL/6 mice were administered with extract (300-600 mg/kg BW) intraperitoneally prior to exposure to 7.5 Gy of γ-radiation to assess radiation modulatory efficacy. The administration of extract (30 min and 1 h) prior to radiation exposure improved the survival of NKE cells (as measured by proliferation), restored MMP and ROS levels as compared to radiation-exposed alone cells. These cells showed up-regulated Nrf2 protein levels at 7 h and increased expression of HO-1 and NOQ1 protein at 24 h In mice, the 30 days whole body survival study demonstrated that extract pre-treatment increases survival or delays the onset of radiation-induced mortality as against 70% mortality of 7.5 Gy of γ-radiation. The aqueous extract of roots of enhanced the survival of irradiated NKE cells and rescued C57BL/6 mice against WBI-induced mortality. The radiation modulation efficacy was mediated through cumulative activation of HO-1 and NQO1 downstream of Nrf2 translocation in NKE cells. ARE: Antioxidant Response Element; FITC: Fluorescein isothiocyanate; GCS: Glutamylcysteine synthase; HO-1: Heme oxygenase-1; LPS: Lipopolysacharide; MRP: Multidrug Resistance-Associated Proteins; NQO1: NAD(P)H Quinone Dehydrogenase 1; NRH: Quinone Oxidoreductase 2 (NQO2); PBS: Phosphate Buffer Saline; PKA: Protein Kinase A; PKC: Protein Kinase C; PI3-kinase: Phosphatidylinositol 3-Kinase; SRB: Sulforhodamine B; UV: Ultra-Violet radiation.

摘要

一种横断喜玛拉雅山脉的植物是一种重要的药用草本植物。在这项研究中,研究了 的水根提取物的放射调节功效。将正常肾上皮细胞用提取物(50-200μg/ml)处理,并暴露于 3Gy 的γ射线中,而 C57BL/6 小鼠在暴露于 7.5Gy 的γ射线之前通过腹膜内给予提取物(300-600mg/kgBW),以评估放射调节功效。在暴露于辐射之前(30 分钟和 1 小时)给予提取物可改善 NKE 细胞的存活(如通过增殖测量),与单独暴露于辐射的细胞相比,恢复 MMP 和 ROS 水平。这些细胞在 7 小时时显示出上调的 Nrf2 蛋白水平,并在 24 小时时增加 HO-1 和 NOQ1 蛋白的表达。在小鼠中,30 天全身生存研究表明,提取物预处理可增加存活或延迟辐射诱导的死亡率的发生,而 7.5Gy 的γ射线的死亡率为 70%。 的根的水提取物增强了辐照的 NKE 细胞的存活,并防止 C57BL/6 小鼠免受 WBI 诱导的死亡率。放射调节功效是通过 Nrf2 易位的 HO-1 和 NQO1 下游的累积激活来介导的。ARE:抗氧化反应元件;FITC:异硫氰酸荧光素;GCS:谷氨酰半胱氨酸合酶;HO-1:血红素加氧酶-1;LPS:脂多糖;MRP:多药耐药相关蛋白;NQO1:NAD(P)H 醌脱氢酶 1;NRH:醌氧化还原酶 2(NQO2);PBS:磷酸盐缓冲盐水;PKA:蛋白激酶 A;PKC:蛋白激酶 C;PI3-kinase:磷酸肌醇 3-激酶;SRB:磺基罗丹明 B;UV:紫外线辐射。

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