Peng Hai-Bing, Wang Rui-Xun, Deng Hai-Jing, Wang Yong-Heng, Tang Jun-Dong, Cao Fu-Yuan, Wang Jian-Hui
Medical Experimental Center of Jitang College, North China University of Science and Technology, Tangshan, Hebei 063210, P.R. China.
Functional Laboratory of School of Basic Medical Sciences, North China University of Science and Technology, Tangshan, Hebei 063210, P.R. China.
Mol Med Rep. 2017 May;15(5):3121-3128. doi: 10.3892/mmr.2017.6402. Epub 2017 Mar 28.
Oleanolic acid (OA), a natural pentacyclic triterpenoid, has been reported to have several benefits and medicinal properties. However, its protective effects against silica‑induced lung injury and fibrosis remain to be elucidated. The aim of the present study was to investigate the effects of OA on oxidative stress, and the expression of cytokines and collagen in silicotic rats. Male rats were induced by intratracheal instillation of silicosis (250 mg/kg), with the exception of the control group (NS). The rats in the OA group were intragastrically administered with OA (60 mg/kg/d). The rats in the solvent control group were gavaged daily with 0.6% sodium carboxymethyl cellulose (10 ml/kg) solution for 56 consecutive days. The data showed that OA significantly attenuated the extent of silicosis fibrosis by histopathologic analysis of the lung tissues. In addition, oxidative stress activated by silica exposure, as evidenced by increasing of malondialdehyde content, and activities of superoxide dismutase and glutathione peroxidase in the lung, was regulated by treatment with OA. Furthermore, enzyme‑linked immunosorbent assay analysis showed that OA significantly decreased the levels of tumor necrosis factor‑α and transforming growth factor‑β1. Immunohistochemistry analysis showed that OA significantly decreased collagen types I and III. In investigating the mechanisms underlying the action of OA, it was found that OA decreased the level of phosphorylated AKT1, which in turn inactivated the transcriptional of nuclear factor (NF)‑κB in the development and progress of silicosis. In conclusion, these results suggested that the protective effects of OA were due, at least in part, to its anti‑oxidant activity and its ability to decrease the expression of cytokines and collagen by modulating the AKT/NF‑κB pathway.
齐墩果酸（OA）是一种天然的五环三萜类化合物，据报道具有多种益处和药用特性。然而，其对二氧化硅诱导的肺损伤和纤维化的保护作用仍有待阐明。本研究的目的是探讨OA对矽肺大鼠氧化应激、细胞因子表达和胶原蛋白的影响。除对照组（生理盐水）外，雄性大鼠通过气管内注入二氧化硅（250mg/kg）诱导矽肺。OA组大鼠灌胃给予OA（60mg/kg/d）。溶剂对照组大鼠连续56天每天灌胃0.6%羧甲基纤维素钠（10ml/kg）溶液。数据显示，通过对肺组织的组织病理学分析，OA显著减轻了矽肺纤维化的程度。此外，二氧化硅暴露激活的氧化应激，表现为肺中丙二醛含量增加以及超氧化物歧化酶和谷胱甘肽过氧化物酶活性增加，通过OA治疗得到调节。此外，酶联免疫吸附测定分析表明，OA显著降低了肿瘤坏死因子-α和转化生长因子-β1的水平。免疫组织化学分析表明，OA显著降低了I型和III型胶原蛋白。在研究OA作用的潜在机制时，发现OA降低了磷酸化AKT1的水平，这反过来又使矽肺发生和发展过程中核因子（NF）-κB的转录失活。总之，这些结果表明，OA的保护作用至少部分归因于其抗氧化活性以及通过调节AKT/NF-κB途径降低细胞因子和胶原蛋白表达的能力。
