大鼠非酒精性单纯性脂肪肝中肾素血管紧张素系统两条通路的相互作用研究  

Study on the Interaction of Two Pathways of Renin Angiotensin System in Rat Nonalcoholic Simple Fatty Liver

作　　者：刘颖[1] 王换换[1] 闫书平 朱斌 张源淑[1] LIU Ying;WANG Huanhuan;YAN Shuping;ZHU Bin;ZHANG Yuanshu(Key Laboratory of Animal Physiology and Biochemistry of Ministry of Agriculture,Nanjing Agricultural University,Nanjing 210095,China)

机构地区：[1]南京农业大学农业部动物生理生化重点开放实验室

出　　处：《畜牧兽医学报》2019年第11期2309-2317,共9页ACTA VETERINARIA ET ZOOTECHNICA SINICA

基　　金：国家自然科学基金(31972640)

摘　　要：本试验探讨了肾素血管紧张素系统(RAS)中ACE/AngⅡ/AT1R和ACE2/Ang1-7/MasR两条通路在大鼠非酒精性单纯性脂肪肝(NAFL)中肝损伤的相互拮抗作用。将30只雄性SD大鼠随机分为正常对照组、模型组和用药组。除正常对照组外,其余2组饲喂高脂饲料,用药组另外给洛伐他汀50 mg·(kg·d)^-1,6周后采集大鼠血液并安乐死,取肝组织。测定各组大鼠血清中TG、ALT、AST的含量;测定肝组织中·OH、TNOS、SOD、T-AOC酶活性;ELISA法测定组织匀浆中AngⅡ、Ang1-7及炎症因子的含量;蛋白印迹分析肝组织ACE、ACE2、AT1R、MasR蛋白水平;HE染色观察肝组织病理学变化。结果显示:模型组肝指数显著升高(P<0.05),血清TG、AST和ALT含量极显著升高(P<0.01),肝细胞表现脂肪变性,肝组织中氧化应激、炎症因子释放显著增强;ACE、AT1R蛋白表达及AngⅡ、Ang1-7含量显著升高(P<0.05或P<0.01),ACE2与MasR的蛋白表达明显降低(P<0.05),ACE/ACE2比值极显著升高(P<0.01),用药组改善氧化应激及炎症损伤,并通过下调ACE/AngⅡ/AT1R通路改善肝组织损伤。高脂饲喂6周可诱导大鼠发生单纯性脂肪肝,肝局部RAS系统两条通路均处于激活状态,ACE/AngⅡ/AT1通路异常激活,导致肝组织氧化应激、炎症反应,而ACE2/Ang1-7/MasR通路具有与前者相反的作用。试验结果提示:肝产生的内源性ACE2在外源性刺激物诱导肝损伤时,可能通过介导Ang1-7/MasR通路的激活在非酒精性单纯性脂肪肝的预防中发挥重要作用。This experiment explored the mutual antagonism of ACE/AngⅡ/AT1 R and ACE2/Ang1-7/MasR pathways in the renin angiotensin system(RAS) in rats nonalcoholic simple fatty liver(NAFL). Thirty male Sprague-Dawley rats were randomly divided into normal control group, model group and medication group. In addition to the normal control group, the other two groups were fed with high-fat diet, and each rat of medication group was given 50 mg·(kg·d)^-1 vitastatin. Blood was collected and all rats were killed after 6 weeks,liver samples were taken at the same time. The contents of TG, ALT and AST in serum of each group were determined. The activities of ·OH, TNOS, SOD and T-AOC in liver tissue were determined. The release of AngⅡ, Ang1-7 and inflammatory factors in tissue homogenate were determined by ELISA. The levels of ACE, ACE2, AT1 R and MasR in liver tissue were analyzed by Western blotting. HE staining was conducted to observe liver pathological changes. Results were as follows:In the model group,the liver index was significantly increased(P<0.05);Serum TG, AST and ALT levels were significantly increased(P<0.01);Liver pathology showed changes in steatosis;Oxidative stress and release of inflammatory factors in liver tissue increased significantly. The expression of ACE, AT1 R protein and the amount of AngⅡ and Ang1-7 increased significantly(P<0.05);The protein expression of ACE2 and MasR decreased significantly(P<0.05), and the ratio of ACE/ACE2 increased(P<0.01). The medication group improved the damage of oxidative stress and inflammation, and improved liver damage by down-regulating the ACE/AngⅡ/AT1 R pathway. High-fat feeding for 6 weeks can induce simple fatty liver in rats, and both the two pathways in the local RAS system are activated. Abnormal activation of the ACE/AngⅡ/AT1 pathway leads to oxidative stress and inflammatory response in the liver, while the ACE2/Ang1-7/MasR pathway has the opposite effect. It is suggested that endogenous ACE2 produced by the liver may play an important role in the p

关 键 词：肾素血管紧张素系统(RAS) 血管紧张素转化酶2(ACE2) 非酒精性单纯性脂肪肝(NAFL) 肝损伤 

分 类 号：S852.23[农业科学—基础兽医学]