摘要
探讨了肾素血管紧张素系统(renin angiotensin system,RAS)两条轴对大鼠非酒精性脂肪肝病(non-alcoholic fatty liver disease,NAFLD)肝脏损伤的相互负向调节作用。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,用药组另外给伐他汀50 mg/kg·d。3周后,宰杀大鼠,测定血清中甘油三酯(TG)、谷丙转氨酶(ALT)、谷草转氨酶(AST)的含量;测定肝组织匀浆羟自由基(·OH)、一氧化氮合酶(NOS)、超氧化物歧化酶(SOD)、总抗氧化能力(T-AOC)酶活性;ELISA法测定组织匀浆中血管紧张素Ⅱ(AngⅡ)、血管紧张素1-7(Ang1-7)及白细胞介素1β(IL-1β)、肿瘤坏死因子α(TNF-α)含量;Western blot分析肝组织血管紧张素转化酶(ACE)、血管紧张素转化酶2(ACE2)、血管紧张素Ⅱ受体1亚型(AT1R)、Mas受体(MasR)蛋白水平。结果:与正常对照组相比,模型组大鼠血清TG、AST和ALT含量以及·OH和NOS活性均显著升高(P<0.05), T-AOC、SOD活性显著降低(P<0.05);IL-1β和TNF-α含量极显著升高(P<0.01);ACE、ACE2的蛋白表达水平与ACE/ACE2的比值均显著升高(P<0.05),AngⅡ、Ang1-7含量与AT1R表达升高(P<0.05),MasR表达有升高趋势(P>0.05)。结论:高脂饲料连续饲喂3周可诱导大鼠发生NAFLD,肝脏局部RAS两条轴均处于激活状态,ACE介导AngⅡ-AT1R经典轴促进肝损伤,而ACE2介导Ang1-7-MasR轴抵抗肝损伤;ACE2负性调节RAS作用,对大鼠NAFLD时肝脏氧化应激及炎性损伤有一定保护作用。
This paper explores the negative regulation effect of the two axes of the renin angiotensin system(RAS) on liver injury in rats with non-alcoholic fatty liver disease(NAFLD).Thirty male SD rats were randomly divided into a normal control group,a model group and a medication group.Except the normal control group,the other two groups were fed with a high-fat diet.The medication group was additionally given Lovastatin 50 mg/kg·d as a positive control every day.Three weeks later,blood samples were drawn and livers were taken from the rats.The contents of TG,ALT and AST in their serum were determined.The liver homogenate was prepared and the activities of ·OH,NOS,SOD and T-AOC were measured.The contents of angiotensinⅡ(AngⅡ),angiotensin 1-7(Ang1-7) and IL-1β and TNF-α in the rat liver tissues were determined using ELISA.The levels of angiotensin converting enzyme(ACE),angiotensin converting enzyme Ⅱ(ACE2),AngⅡ type 1 receptor(AT1R) and MasR in the liver tissues were analyzed by Western blot.The results were as follows: Compared with the normal control group,the levels of TG,ALT and AST in the serum of the model group significantly increased(P<0.05);the oxidative stress index,the activities of ·OH and NOS in rat livers increased significantly(P<0.05);the activities of anti-oxidative stress T-AOC and SOD significantly decreased(P < 0.05);the levels of inflammatory factors IL-1β and TNF-αsignificantly increased(P <0.01);the protein expression levels of ACE,ACE2 and the ratio of ACE/ACE2 in liver tissues of the model group were significantly higher than those in the normal control group and the medication group(P<0.05);the expression of AT1R increased(P<0.05);MasR expression increased although the difference was not significant(P>0.05);the level of Ang1-7 and AngⅡ in the liver tissues of the model group increased significantly(P<0.05).In conclusion,continuous feeding of a high-fat diet for 3 weeks induced NAFLD in rats.The two axes of liver local RAS were activated.ACE mediated the classical axis AngⅡ-AT1R which aggravated liver injury.However,ACE2 mediated the Ang1-7-MasR axis against liver damage.ACE2 negatively regulated RAS and had a protective effect on hepatic oxidative stress and inflammatory injury in rats with NAFLD.
作者
刘颖
王凯
纪晓霞
张源淑
LIU Ying;WANG Kai;JI Xiaoxia;ZHANG Yuanshu(Key Laboratory of Animal Physiology and Biochemistry,Ministry of Agriculture,Nanjing Agricultural University,Nanjing 210095,China)
出处
《畜牧与兽医》
北大核心
2019年第5期48-54,共7页
Animal Husbandry & Veterinary Medicine
基金
国家自然科学基金(30871838)
