栀子苷对动脉粥样硬化并发非酒精性脂肪肝ApoE^(-/-)小鼠炎症和氧化应激的影响  

Effects of Geniposide on Inflammation and Oxidative Stress of Apo E Knockout Mice with Atherosclerosis and None-alcoholic Fatty Liver Disease

作　　者：张宇[1] 程赛博[1] 周凤华[1] 张蕾[1] 苏志杰[1] 赵丹丹[1] 陈育尧[1] 贾钰华[1] 

机构地区：[1]南方医科大学,广东广州510515

出　　处：《中药新药与临床药理》2015年第5期581-586,共6页Traditional Chinese Drug Research and Clinical Pharmacology

基　　金：国家自然科学基金(81373574);国家自然科学基金青年基金(81403339);广东省自然科学基金博士启动项目(2014.A030310150);广东省自然科学基金项目(2014A030313354);广东省中医药管理局科研项目(20141186);广州市海珠区科技计划项目(2015-C9-35)

摘　　要：目的观察栀子苷对动脉粥样硬化(AS)并发非酒精性脂肪肝(NAFLD)Apo E-/-小鼠炎症和氧化应激的影响。方法将50只Apo E-/-小鼠随机分为模型组,辛伐他汀组(5 mg·kg-1·d-1),栀子苷低、中、高剂量组(12.5,25,50 mg·kg-1·d-1),每组10只,另取10只C57BL/6J小鼠作为正常对照组。采用高脂饲料喂养16周的方式建立AS模型,分别于胸主动脉与肝脏部位切片观察主动脉斑块及肝脏病理形态,检测各组小鼠血脂、肝功能以及血清和肝脏中炎症因子、丙二醛(MDA)、总超氧化物歧化酶(T-SOD)水平。结果与正常对照组比较,模型组小鼠总胆固醇(TC)、甘油三酯(TG)、天冬氨酸氨基酶(AST)、丙氨酸氨基转移酶(ALT)水平明显增高(P<0.01),血清和肝匀浆中肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、MDA显著升高(P<0.01),T-SOD水平降低(P<0.01)。模型组主动脉内可见纤维斑块形成,肝细胞可见大量脂肪变性;辛伐他汀与栀子苷各剂量组均能降低血清及肝脏中TNF-α、IL-6、MDA水平,升高T-SOD水平,并且能抑制主动脉斑块形成,减轻肝脏脂肪变性。结论对AS并发NAFLD Apo E-/-小鼠,栀子苷具有显著治疗作用,其机制可能为抑制炎症,抗氧化应激损伤。Objective To study the effects of geniposide on the inflammation and oxidative stress of ApoE knockout （ApoE-α-） mice with atherosclerosis（AS） and none-alcholic fatty liver disease（NAFLD）. Methods Fifty ApoE-/- mice were evenly randomized into model group, low-dose geniposide group（12.5 mg·kg-1·d-1）, medium-dose geniposide group （25 mg· kg-1· d-1）, high-dose geniposide group （50mg· kg-1· d-1）, and simvastatin group （5 mg· kg-1· d-1）. Ten C57BL/6J mice served as the normal control group. High fat diet was given to ApoE-/- mice for 16 weeks to establish AS model. After 16 weeks of feeding, all of the mice were killed, and the thoracic aorta and liver were sliced for pathological examination. The serum levels of total cholesterol （TC）, triglyceride （TG）, low density lipoprotein- cholesterol （LDL-C）, high density lipoprotein-cholesterol （ HDL-C ）, alanine aminotransferase （ALT） and aspartate aminotransferase （AST） as well as interleukin-6 （IL-6）, tumor necrosis factor-alpha （TNF-α）, total superoxide dismutase（T-SOD）, malonaldehyde（MDA） in the serum and liver homogenate were detected. Results Compared with the normal control group, TC, TG, ALT and AST in the model mice were significantly increased （P 〈 0.01 ） ; IL-6, TNF-α and MDA were also increased while T-SOD was decreased in the serum and liver homogenate（P 〈 0.01 ）. In the model group, intra-aortic fibrous plaque formation and obvious fatty degeneration in the liver cells were seen. Simvastatin and geniposide could not only decrease the levels of IL-6, TNF-α and MDA and increase T-SOD, but also inhibit aortic plaque information and hepatic fatty degeneration. Conclusion Geniposide shows obvious effect on ApoE- mice with AS and NAFLD, and the therapeutic mechanism may be related to anti-inflammation and suppressing oxidative stress.

关 键 词：动脉粥样硬化 非酒精性脂肪肝 栀子苷 炎症 氧化应激 

分 类 号：R285.5[医药卫生—中药学]