异荭草素对T2DM并非乙醇性脂肪肝小鼠的保护作用及其机制  

PROTECTIVE EFFECT OF ISOORIENTIN ON MICE WITH TYPE 2 DIABETES MELLITUS AND NONALCOHOLIC FATTY LIVER DISEASE AND ITS MECHANISM

作　　者：田静[1,2] 张学辉 车奎 迟静薇 王颜刚[1] TIAN Jing;ZHANG Xuehui;CHE Kui;CHI Jingwei;WANG Yangang(Department of Endocrine and Metabolic Diseases,The Affiliated Hospital of Qingdao University,Qingdao 266003,China)

机构地区：[1]青岛大学附属医院内分泌与代谢病科,山东青岛266003 [2]山东第一医科大学附属成武医院内分泌科 [3]山东第一医科大学附属成武医院心血管内科 [4]青岛大学附属医院医学研究中心

出　　处：《青岛大学学报（医学版）》2022年第1期7-12,共6页Journal of Qingdao University(Medical Sciences)

基　　金：国家自然科学基金面上项目(81870615)。

摘　　要：目的研究异荭草素对2型糖尿病(T2DM)合并非乙醇性脂肪肝小鼠的保护作用及其机制。方法雄性C57BL/6J小鼠通过腹腔注射链脲佐菌素(STZ)和喂养60%的高脂饲料制备T2DM合并非乙醇性脂肪肝模型。成模小鼠随机分为模型对照组和异荭草素低、中、高剂量组,异荭草素低、中、高剂量组分别按10、20、40 mg/kg剂量腹腔注射给药。8周后处死小鼠采集血及肝组织标本。用全自动生化分析仪检测小鼠空腹血清血糖(FBG)水平;油红O染色观察肝组织脂滴沉积;比色试剂盒检测肝组织总胆固醇(TC)、三酰甘油(TG)、游离脂肪酸(FFA)含量,以及总抗氧化能力(T-AOC)、总超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、还原型谷胱甘肽(GSH)、丙二醛(MDA)水平;Western blotting检测肝组织转录因子NF-E2相关因子(Nrf-2)、血红素加氧酶-1(HO-1)、葡萄糖转运载体2(GLUT2)蛋白的表达水平。结果与模型对照组相比较,异荭草素处理各组小鼠的肝组织脂滴沉积明显减少,TC、TG、FFA含量显著降低(F=62.612~882.536,P<0.001);血清FBG显著降低(F=1183.454,P<0.001);肝组织中T-AOC、SOD、CAT、GSH等抗氧化指标水平显著升高(F=49.356~1869.515,P<0.001),而脂质过氧化产物MDA水平显著降低(F=287.756,P<0.001);肝组织中Nrf-2、HO-1、GLUT2蛋白的表达水平显著上调,差异均具有统计学意义(F=6.560~42.410,P<0.01)。结论异荭草素一方面通过激活Nrf-2/HO-1信号通路抑制氧化应激,另一方面通过增加肝脏GLUT2蛋白表达降低血糖、减轻胰岛素抵抗,进而发挥对T2DM合并非乙醇性脂肪肝小鼠的保护效应。Objective To investigate the protective effect of isoorientin on mice with type 2 diabetes mellitus(T2 DM)and nonalcoholic fatty liver disease(NAFLD)and its mechanism.Methods Male C57 BL/6 J mice were used to establish a mo-del of T2 DM with NAFLD by intraperitoneal injection of streptozotocin(STZ)and feeding with 60%high-fat diet.After successful modeling,the mice were randomly divided into model control group and low-,middle-,and high-dose isoorientin groups(treated with intraperitoneal injection of isoorientin at doses of 10,20,and 40 mg/kg,respectively).The mice were sacrificed after 8 weeks to collect blood and liver tissue samples.An automatic biochemical analyzer was used to measure the serum level of fasting blood glucose(FBG);oil red O staining was used to observe the deposition of lipid droplets in liver tissue;the colorimetric kit was used to measure the content of total cholesterol(TC),triglycerides(TG),and free fatty acid(FFA)in liver tissue,as well as the levels of total antioxidant capacity(T-AOC),total superoxide dismutase(SOD),catalase(CAT),reduced glutathione(GSH),and malondialdehyde(MDA);Western blotting was used to measure the protein expression levels of the transcription factors NF-E2-rela-ted factors-2(Nrf-2),heme oxygenase-1(HO-1),and glucose transporter 2(GLUT2)in liver tissue.Results Compared with the model control group,the isoorientin treatment groups had significant reductions in the deposition of lipid droplets and the content of TC,TG,and FFA in liver tissue(F=62.612-882.536,P<0.001),as well as a significant reduction in serum FBG(F=1183.454,P<0.001).Compared with the model control group,the isoorientin treatment groups also had significant increases in the antioxidant indices T-AOC,SOD,CAT,and GSH in liver tissue(F=49.356-1869.515,P<0.001)and a significant reduction in the level of the lipid peroxidation product MDA(F=287.756,P<0.001),as well as significant increases in the protein expression le-vels of Nrf-2,HO-1,and GLUT2 in liver tissue(F=6.560-42.410,P<0.01).Conclusion On one h

关 键 词：异荭草素 糖尿病 2型 非乙醇性脂肪性肝病 氧化性应激 葡萄糖转运体2型 小鼠 

分 类 号：R587.1[医药卫生—内分泌] R575.5[医药卫生—内科学]