黄芪多糖激活Nrf2/HO-1信号通路改善模型大鼠糖尿病性肝损伤  

Astragalus polysaccharide attenuates hepatic damage by activating Nrf2/HO-1 pathway in diabetic rats

作　　者：曲敬蓉 张艳艳[2,5] 宿宏佳[1] 李静静 李浩 张腾 刘英 毛淑梅[1] QU Jing-rong;ZHANG Yan-yan;SU Hong-jia;LI Jing-jing;LI Hao;ZHANG Teng;LIU Ying;MAO Shu-mei(Dept of Pharmacology, Weifang Medical University, Weifang Shandong 261053, China;Postdoctoral Research Station of Shandong University of Traditional Chinese Medicine, Jinan 250355, China;Dept of Anesthesiology, Gaomi People’s Hospital, Gaomi Shandong 261500, China;Dept of Pharmacology, Dalian Medical University, Dalian Liaoning 116044, China;Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250011, China)

机构地区：[1]潍坊医学院药理学教研室,山东潍坊261053 [2]山东中医药大学博士后科研流动站,山东济南250355 [3]高密市人民医院麻醉科,山东高密261500 [4]大连医科大学药学院,辽宁大连1160441 [5]山东中医药大学附属医院,山东济南250011

出　　处：《中国药理学通报》2020年第10期1422-1427,共6页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81274049);山东省自然科学基金资助项目(No ZR2013CM033,ZR2015CL029);山东省教育厅科技计划项目(No J15LL54,J16LM11);山东省中医药管理局项目(No 2013-242,2015-237)。

摘　　要：目的探讨黄芪多糖(astragalus polysaccharide,APS)对糖尿病大鼠肝脏中转录因子NF-E2相关因子2(nuclear factor erythroid-2-related factor 2,Nrf2)、血红素氧合酶(heme oxygenase,HO)-1的影响,及对糖尿病性肝损伤的治疗作用。方法制备2型糖尿病大鼠模型,分别给予二甲双胍(metformin)和不同剂量的APS进行治疗。12周后,通过HE染色、PAS染色、Masson染色观察各组大鼠肝组织形态学改变,WST-1法和TBA法检测SOD和MDA水平,通过检测肝组织中Nrf2、p-Nrf2、HO-1的蛋白和Nrf2、HO-1的mRNA表达水平,评价Nrf2/HO-1信号通路活性。结果形态学检测结果显示模型组大鼠存在肝脏病理损伤,二甲双胍可改善糖尿病大鼠肝损伤,证实阳性对照药物成立,高剂量APS亦明显改善了糖尿病大鼠肝脏的病理损伤,表明APS对糖尿病病理状态下的肝脏有保护作用,此外,APS明显激活了糖尿病大鼠肝脏Nrf2/HO-1信号通路。结论APS可明显改善糖尿病大鼠肝脏损伤,其机制可能与激活Nrf2/HO-1信号通路有关。Aim To investigate the effects of astragalus polysaccharide(APS)on the hepatic damage and the activity of the nuclear factor erythroid-2-related factor 2(Nrf2)-heme oxygenase(HO)-1 signaling pathway in diabetic rats.Methods Type 2 diabetic rats were treated with metformin or different doses of APS,respectively for 12 weeks.The pathological changes of the liver were accessed by HE staining,PAS staining and Masson staining.Levels of the oxidative stress markers SOD and MDA were measured by WST-1 assay and TBA assay.The activity of Nrf2/HO-1 signaling pathway was evaluated by detecting both the protein and mRNA expression of Nrf2 and HO-1,as well as measuring the levels of phosphorylated-Nrf2(p-Nrf2)in hepatic tissues.Results The morphological results showed that the rats in model group had obvious hepatic damage,which could be improved by the positive control drug metformin.High-dose of APS also attenuated liver injury of diabetic rats,which confirmed the hepatoprotective activity of APS.Additionally,APSsignificantly boosted the hepatic activity of Nrf2/HO-1 signaling pathway in diabetic rats.Conclusions APS can significantly improve the liver injury in diabetic rats,and its mechanism may be related to the activation of Nrf2/HO-1 signaling pathway.

关 键 词：黄芪多糖 2型糖尿病 肝损伤 NRF2 HO-1 氧化应激 

分 类 号：R-332[医药卫生] R284.1