Construction and evaluation of diabetic atherosclerosis model in LDLR-/-mice in-duced by STZ and fed with high-fat diet
10.20039/j.cnki.1007-3949.2024.11.009
- VernacularTitle:STZ诱导联合高脂喂养LDLR-/-小鼠糖尿病动脉粥样硬化模型的构建及评价
- Author:
Li WANG
1
;
Jinning GAO
;
Xiangyun CHEN
;
Peiqing JIANG
;
Mei LI
;
Fangfang BU
;
Mei ZHANG
;
Guihua YAO
;
Hui SUN
Author Information
1. 山东大学齐鲁医院(青岛)心内科,山东省青岛市 266053
- Keywords:
streptozotocin;
high-fat diet;
diabetes;
atherosclerosis;
LDLR-/-mice
- From:
Chinese Journal of Arteriosclerosis
2024;32(11):985-993
- CountryChina
- Language:Chinese
-
Abstract:
Aim To construct a diabetic atherosclerosis mouse model and study the pathological characteristics of diabetic atherosclerosis.Methods Fifty 8-week-old male LDLR-/-mice were fed with standard diet for 2 weeks and then changed to high-fat diet,they were randomly divided into two groups.The diabetic atherosclerosis group was given intraperitoneal injection of low dose streptozotocin(STZ)for 5 days continuouly to establish the model,and the atheroscle-rosis group was given citrate buffer injection at the same time.The body mass,blood glucose and blood lipids of the mice in the two groups were detected for many times.At the age of 23 weeks,the mice were euthanized after glucose tolerance test.HE staining and oil red O staining were used to detect the gross and aortic root atherosclerosis,immunohistochemical staining was used to detect CD4,α-smooth muscle actin(α-SMA),EGF-like module-containing mucin-like hormone re-ceptor-like 1(EMR1),monocyte chemotactic protein-1(MCP-1),NOD-like receptor protein 3(NLRP3),vascular cell adhesion molecule-1(VCAM-1),matrix metalloproteinase-2(MMP-2)and tissue inhibitor of metalloproteinase-1(TIMP-1),Western blot was used to detect α-SMA,CD4,tumor necrosis factor-α(TNF-α),NLPR3,intercellular adhesion molecule-1(ICAM-1),and type Ⅰ and Ⅲ collagen.Results Compared with the atherosclerosis group,the body mass decreased,the levels of total cholesterol(TC),triglyceride(TG),low density lipoprotein cholesterol(LDLC)increased,and the levels of high density lipoprotein cholesterol(HDLC)decreased(P＜0.05)in the diabetic atherosclerosis group.Compared with the atherosclerosis group,the distribution of atherosclerotic plaques was diffuse and the area was increased in the diabetic atherosclerosis group,and the contents of lipids,T cells,macrophages,smooth muscle cells,type Ⅰ and Ⅲ colla-gen were increased(P＜0.05);the protein levels of TNF-α,MCP-1,MMP-2,NLRP3,ICAM-1 and VCAM-1 in vascular tissues were increased,while the content of TIMP-1 were decreased and MMP2/TIMP-1 were increased(P＜0.05).Conclusions LDLR-mouse model of diabetic atherosclerosis can be successfully established by STZ induction combined with high-fat diet,which can reflect the plaque composition and inflammatory characteristics of diabetes promoting atheroscle-rosis.It can be used as a relatively ideal pathological model for the study of diabetic macroangiopathy.
