白毛黑眼兔与日本大耳白兔胰岛素抵抗动脉粥样硬化模型的比较

Comparison of the WHBE and Japanese white rabbit models of insulin resistance atherosclerosis

目的探讨白毛黑眼(WHBE)兔和日本大耳白(JW)兔胰岛素抵抗动脉粥样硬化(insulin resistance atherosclerosis,IR-AS)模型的表型差异和病理机制。方法取WHBE兔与JW兔各12只,分为正常对照组(NC)和高脂高糖饮食(HF)组,每组6只。用HF饮食12周诱发IR-AS模型。造模结束后,取血测定血脂、超氧化物歧化酶(SOD)和丙二醛(MDA)水平;行糖耐量试验,计算血糖和胰岛素曲线下面积;检测肝微粒体甘油三酯转运蛋白( MTTP )、核因子E2(Nrf2)和SOD1基因的表达,并观察脂肪和主动脉血管的HE染色病理变化以及血管CD68的表达情况。结果与NC组比,HF组肥胖,血脂升高,糖耐受不良,高胰岛素血症和胰岛素抵抗指数(HOMA-IR)明显升高,血浆及肝SOD活性下降且MDA含量升高,肝MTTP和 Nrf2 基因表达升高且SOD1基因表达降低,血管脂质沉积和AS以及血管CD68表达显著升高;与JWHF组比,WBHF组TG、LDL-C、HOMA-IR、糖耐量曲线下面积(U_GLU)、MDA含量、脂肪直径大小、肝SOD1基因表达、AS病变程度及血管CD68表达上有明显差异。结论高脂高糖饮食能诱导兔形成IR-AS,表现出脂代谢紊乱、炎症和AS病变。但WHBE兔的病变程度明显严重于JW兔,这可能与这两种品系兔在脂质代谢和氧化应激反应存在差异有关。

Objective To explore the phenotypic differences and pathological mechanisms of insulin resistance and atherosclerosis (IR-AS) in white hair black eye (WHBE) rabbits and Japanese white (JW) rabbits.Methods Twelve JW rabbits and 12 WHBE rabbits were randomly divided into the normal control group (NC) and high fat and sugar diet (HF) group with six rabbits in each group.The IR-AS model was induced by feeding a high fat and sugar diet for 12 weeks.At the end of modeling,blood samples were collected to determine blood lipid,superoxide dismutase (SOD),and malondialdehyde (MDA) levels.A glucose tolerance test was conducted,and the area under the curves of blood glucose and insulin was calculated.mRNA expression of microsomal triglyceride transfer protein ( MTTP ),nuclear factor-like 2 ( Nrf2 ),and SOD1 genes in the liver was detected,pathological changes in fat tissues and aortic wall by HE staining,and CD68 expression in aortic tissues were observed.Results Compared with the NC group,HF rabbits showed significant obesity,hyperlipidemia,glucose intolerance,hyperinsulinemia,and increased HOMA-IR.Moreover,HF rabbits exhibited decreased SOD activity and increased MDA contents in their plasma and liver,increased mRNA expression of MTTP and Nrf2 in the liver tissue,and decreased mRNA expression of SOD1.In addition,vascular lipid deposition,AS plaque size,and CD68 expression were increased significantly.Compared with the JWHF group,TG,LDL-C,HOMA-IR,U_GLU,MDA content,fat diameter,SOD1,AS lesion degree,and vascular CD68 expression in the WBHF group were significantly different.Conclusions A high-fat and sugar diet induces the formation of IR-AS in rabbits, resultsing in an obvious lipid metabolism impairment,inflammatory and AS lesions.However,the degree of pathological changes in WHBE rabbits is significantly more serious than that in JW rabbits,which may be related to the differences in lipid metabolism and the oxidative stress response between the two rabbit strains.