隐丹参酮调节AMPK/Nrf2信号通路治疗小鼠非酒精性脂肪性肝病作用机制  

Mechanism of cryptotanshinone regulates AMPK/Nrf2 signaling pathway to treat nonalcoholic fatty liver disease in mouse

作　　者：赵梦溪 罗斌 吕建瑞[1] 王宁[1] ZHAO Mengxi;LUO Bin;LYU Jianrui;WAN Ning(The Second Affiliated Hospital of Xi’an Jiaotong University,Xi’an 710004,China)

机构地区：[1]西安交通大学第二附属医院,陕西西安710004

出　　处：《陕西中医》2023年第8期1027-1031,1036,共6页Shaanxi Journal of Traditional Chinese Medicine

基　　金：陕西省重点研发计划项目(S2022-YF-YBSF-0504)。

摘　　要：目的:研究隐丹参酮调节腺苷酸活化蛋白激酶(AMPK)/核因子E2相关因子2(Nrf2)信号通路治疗小鼠非酒精性脂肪性肝病(NAFLD)作用机制。方法:60只C57BL/6小鼠随机分为正常组12只和造模组48只。造模组连续给予8周高脂饲料+红糖水构建NAFLD模型,然后随机分为模型组和隐丹参酮低、中和高剂量组,每组12只。治疗4周后,检测小鼠血清谷草转氨酶(AST)、谷丙转氨酶(ALT)、丙二醛(MDA)、超氧化物歧化酶(SOD)和谷胱甘肽(GSH)水平,检测小鼠肝脏和血清总胆固醇(TC)、甘油三酯(TG)水平,油红O和HE染色观察肝脏组织病理学改变,同时采用Western blot检测肝脏组织AMPK、磷酸化腺苷酸活化蛋白激酶(p-AMPK)、Nrf2蛋白表达。结果:与正常组比较,模型组小鼠肝脏和血清TG、TC水平,血清AST、ALT和MDA水平明显升高,血清SOD、GSH水平明显降低(均P<0.05);与模型组比较,不同剂量隐丹参酮组小鼠血清和肝脏TG、TC水平,血清AST、ALT、MDA水平明显降低,血清SOD、GSH水平明显升高(均P<0.05)。HE染色和油红O染色显示,正常组小鼠肝脏切片光滑;模型组小鼠有大量脂肪颗粒聚集;与模型组比较,各剂量隐丹参酮组小鼠脂滴数量均明显降低。与模型组比较,隐丹参酮低、中、高剂量组小鼠Nrf2、p-AMPK表达明显升高(均P<0.05)。隐丹参酮低、中、高剂量组与模型组小鼠AMPK蛋白表达比较,差异无统计学意义(P>0.05)。结论:隐丹参酮可能通过调节AMPK/Nrf2信号通路,提高抗氧化能力,减少肝脏脂质蓄积发挥肝脏保护作用。Objective:To study the mechanism of cryptotanshinone regulating AMPK/Nrf2 signaling pathway in the treatment of mouse with nonalcoholic fatty liver disease.Methods:Sixty C57BL/6 mouse were randomly divided into normal group(n=12)and model group(n=48).The model group was given high-fat diet and brown sugar water for 8 weeks to establish NAFLD model,and then randomly divided into model group,low,medium and high dose cryptotanshinone group,with 12 mouse in each group.After 4 weeks of treatment,serum levels of aspartate aminotransferase(AST),alanine aminotransferase(ALT),malondialdehyde(MDA),superoxide dismutase(SOD)and glutathione(GSH)of mice were detected,liver and serum total cholesterol(TC)and triglyceride(TG)of mice were detected,and liver histopathological changes were observed by oil red O and HE staining.Meanwhile,Western blot was used to detect AMPK,p-AMPK and Nrf2 protein expression in liver tissue.Results:Compared with normal group,the levels of TG and TC in liver and serum,serum AST,ALT and MDA levels in were observably increased in model group,while the levels of SOD and GSH in serum were significantly decreased(all P<0.05).Compared with model group,the levels of TG and TC in liver and serum,serum AST,ALT and MDA levels were significantly decreased in different doses of cryptotanshinone group,while the levels of SOD and GSH were significantly increased(all P<0.05).HE staining and oil red O staining showed that the liver sections of normal group were smooth.In the model group,a large number of fat particles were accumulated.Compared with model group,the number of lipid drops decreased significantly at each dose cryptotanshinone groups.Compared with model group,the expressions of Nrf2 and p-AMPK in low,medium and high dose cryptotanshinone groups were significantly increased(all P<0.05).There was no significant difference in AMPK expression between low,medium and high dose cryptotanshinone groups and model group(P>0.05).Conclusion:Cryptotanshinone may play a protective role in liver by regulating AMPK/Nrf2

关 键 词：非酒精性脂肪性肝病 隐丹参酮 腺苷酸活化蛋白激酶 核因子E2相关因子2 小鼠 氧化损伤 

分 类 号：R575.1[医药卫生—消化系统]