STZ诱导糖尿病联合正常饮食促ApoE-/-小鼠动脉粥样硬化的作用  

Pro-atherosclerotic effects of streptozotocin-induced diabetes combined with chow diet on apoE-/- mice

作　　者：孙慧[1] 赵磊[1] 甄茜[1] 王莎莎[1] 黄山英[1] 贺红[1] 胡琴[1] 

机构地区：[1]山东大学齐鲁医院心内科国家教育部和卫生部心血管重塑和功能研究重点实验室,山东济南250012

出　　处：《山东大学学报（医学版）》2014年第10期1-8,28,共9页Journal of Shandong University:Health Sciences

基　　金：国家自然科学基金(81100204;81370410)

摘　　要：目的探讨链脲佐菌素(STZ)诱导糖尿病联合正常饮食对ApoE-/-小鼠动脉粥样硬化病变的作用。方法取60只8周龄雄性ApoE-/-小鼠正常饮食饲养2周后,随机分为糖尿病组(采用小剂量STZ持续腹腔注射5 d)和非糖尿病对照组(柠檬酸盐缓冲液注射5 d),每组30只,正常饮食喂养13周后处死。分别检测小鼠血脂、炎症因子和血糖变化;HE和油红O染色检测各组小鼠大体和主动脉根部斑块病变;免疫组化、RT-PCR和Western blotting技术分别检测斑块内血管平滑肌细胞、巨噬细胞、基质金属蛋白酶-9/基质金属蛋白酶抑制剂-1(MMP-9/TIMP-1)、肿瘤坏死因子(TNF-α)和巨噬细胞趋化性因子(MCP-1)基因或蛋白含量变化。结果非糖尿病对照组主动脉及其根部病变轻微。与非糖尿病对照组比较,糖尿病组斑块面积明显增加,其中脂质、巨噬细胞、Ⅰ和Ⅲ型胶原、血管壁平滑肌细胞含量增加,但纤维帽处平滑肌细胞减少,斑块易损指数增加;血清MIF和IL-6水平升高,血管组织TNF-α、MCP-1、MMP-2和MMP-9基因表达或蛋白含量增加,而TIMP-1含量下降。结论 STZ诱导糖尿病ApoE-/-小鼠联合正常饮食有促动脉粥样硬化作用,并增加斑块易损性和机体炎症状态。Objective To explore the effects of streptozotocin（STZ）-induced diabetes combined with chow diet on ath-erosclerotic lesions of apoE-/-mice.Methods After 2 weeks of chow diet,60 male apoE-/- mice （10 weeks old） were randomly divided into two groups. Diabetic apoE-/-mice （n=30）were constructed by intraperitoneal injection of low-dose STZ for 5 consecutive days.ApoE-/-mice （n=30）injected with citrate buffer liquid served as non-diabetic controls.All mice were fed with chow diet until sacrifice （23 weeks old）.Serum lipid,inflammation cytokines and blood glucose were measured.Atherosclerotic plaques in the aorta and aortic root were examined with HE staining and Oil-Red-O staining.The mRNA and protein levels of vascular smooth muscle cells （SMCs）,macrophages,MMP-9/TIMP-1 ,TNF-αand MCP-1 in the plaques were detected with immunohistochemical staining,RT-PCR and Western blotting,respectively.Results The non-diabetic apoE-/- mice showed slight atherosclerotic lesions,while diabetic apoE-/-mice had significantly aggravated atherosclerotic lesions.Compared with non-diabetic mice,diabetic apoE-/-mice had markedly larger size of plaques,in which lipid,macrophages,typeⅠandⅢcollagens and SMCs increased,while SMCs in fiber cap decreased,and atherosclerotic plaque instability index rose.Moreover,serum IL-6 and MIF levels,TNF-α,MCP-1,MMP-2 and MMP-9 mRNA all increased while TIMP-1 decreased.Conclusion STZ-induced diabetic apoE-/-mice fed with chow diet show deteriorated atherosclerotic lesions and relatively unstable plaques.

关 键 词：链脲佐菌素 糖尿病 动脉粥样硬化 APOE-/-小鼠 

分 类 号：R541.4[医药卫生—心血管疾病]