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硒化黄芪多糖对四氯化碳诱导的大鼠肝损伤的改善作用:促炎细胞因子、氧化应激和肝星状细胞的作用

Amelioration of CCl-induced liver injury in rats by selenizing Astragalus polysaccharides: Role of proinflammatory cytokines, oxidative stress and hepatic stellate cells.

作者信息

Hamid Mohammed, Liu Dandan, Abdulrahim Yassin, Liu Yunhuan, Qian Gang, Khan Alamzeb, Gan Fang, Huang Kehe

机构信息

College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, Jiangsu Province, China; Institute of Nutritional and Metabolic Disorders in Domestic Animals and Fowl, Nanjing Agricultural University, Nanjing 210095, China; College of Veterinary Sciences, University of Nyala, Sudan.

College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, Jiangsu Province, China; Institute of Nutritional and Metabolic Disorders in Domestic Animals and Fowl, Nanjing Agricultural University, Nanjing 210095, China.

出版信息

Res Vet Sci. 2017 Oct;114:202-211. doi: 10.1016/j.rvsc.2017.05.002. Epub 2017 May 2.

DOI:10.1016/j.rvsc.2017.05.002
PMID:28482267
Abstract

Selenizing Astragalus polysaccharides (sAPS) were prepared by nitric acid-sodium selenite method. Effect of sAPS on carbon tetrachloride (CCl4)-induced liver injury and the underlying mechanisms were investigated in the rat. Forty male Wistar rats were divided into five equal groups as follows: control group; CCl group; CCl+Astragalus polysaccharides group; CCl+sodium selenite group and CCl+selenizing Astragalus polysaccharides group. The results showed that sAPS significantly decreased the levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, lactate dehydrogenase in the serum, malondialdehyde and hydroxyproline content in liver (P<0.01), and increased the levels of total protein, total antioxidant capacity, glutathione peroxidase, and superoxide dismutase in liver of rats induced by CCl In addition, expression levels of antioxidant-related genes (GPX1, SOD1, and Nrf2) were significantly increased following supplementation of the sAPS (P<0.01). Furthermore, sAPS effectively ameliorated CCl induced hepatic necrosis and inflammation, and it also reduced the expression levels of proinflammatory cytokines including TNF-α, IL-6, COX-2 and NFκB (P<0.01) Moreover, sAPS significantly decreased the expression levels of α-smooth muscle actin, collagen 1, TGF-β1, but increased the Bcl-2/Bax mRNA ratio in rats administered CCl (P<0.01). Taken together, it could be concluded that sAPS could increase the activities of Astragalus polysaccharides and sodium selenite to protect the liver from damage by attenuating hepatic inflammation, oxidative stress, fibrogenesis, and induces apoptosis and cell cycle arrest in hepatic stellate cells.

摘要

采用硝酸-亚硒酸钠法制备了硒化黄芪多糖(sAPS)。在大鼠中研究了sAPS对四氯化碳(CCl4)诱导的肝损伤的影响及其潜在机制。将40只雄性Wistar大鼠分为五组,每组数量相等,分组如下:对照组;CCl组;CCl+黄芪多糖组;CCl+亚硒酸钠组和CCl+硒化黄芪多糖组。结果表明,sAPS显著降低了血清中谷丙转氨酶、谷草转氨酶、碱性磷酸酶、乳酸脱氢酶的水平,以及肝脏中丙二醛和羟脯氨酸的含量(P<0.01),并提高了CCl诱导的大鼠肝脏中总蛋白、总抗氧化能力、谷胱甘肽过氧化物酶和超氧化物歧化酶的水平。此外,补充sAPS后,抗氧化相关基因(GPX1、SOD1和Nrf2)的表达水平显著升高(P<0.01)。此外,sAPS有效改善了CCl诱导的肝坏死和炎症,还降低了包括TNF-α、IL-6、COX-2和NFκB在内的促炎细胞因子的表达水平(P<0.01)。此外,sAPS显著降低了给予CCl的大鼠中α-平滑肌肌动蛋白、胶原蛋白1、TGF-β1的表达水平,但提高了Bcl-2/Bax mRNA比值(P<0.01)。综上所述,可以得出结论,sAPS可以增强黄芪多糖和亚硒酸钠的活性,通过减轻肝脏炎症、氧化应激、纤维化形成,并诱导肝星状细胞凋亡和细胞周期停滞来保护肝脏免受损伤。

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