代谢综合征大鼠模型的建立及其相关基因表达变化的研究

目的建立与人类代谢综合征(MS)相似的大鼠模型,并分析其相关基因的表达变化。方法雄性8周龄Wistar大鼠30只随机分为普通膳食对照组(NC组)和高脂高盐膳食组(MS组)。喂养期间对大鼠体重、血压、空腹血糖(FPG)、血脂、胰岛素水平等进行连续监测;24周喂养结束进行高胰岛素-正常血糖钳夹试验和腹腔注射糖耐量试验,检测颈动脉血压,测量内脏脂肪重量;取其白色脂肪(肠系膜)、棕色脂肪和骨骼肌组织,以RT-PCR法检测胰岛素敏感组织基因表达变化。结果MS组体重、内脏脂肪、血压、血浆甘油三酯(TG)、游离脂肪酸(FFA)与NC组比较显著增加(P<0·05或P<0·01),且存在严重的胰岛素抵抗[GIR:1·26±0·82mg/(kg·min)vs7·03±1·68mg/(kg·min),P<0·01]和糖耐量减退,表现为典型的MS特征;胰岛素敏感组织基因检测结果显示,与NC组比较,MS组与糖脂代谢和能量代谢相关的23种基因的mRNA表达水平在白色脂肪(肠系膜)、棕色脂肪和骨骼肌组织中多数变化显著。结论长期高脂和高盐饮食喂养可诱导类似于人类MS的基本临床特征大鼠模型,其机制可能与高脂摄入导致大鼠胰岛素敏感组织的糖脂代谢和能量代谢相关基因的变化有关。

Reproduction of a rat model of metabolic syndrome to study the related gene expression

Objective To reproduce a rat model of metabolic syndrome (MS) to analyze the variations of related gene expression. Methods 30 male rats aged 8w were randomly divided into two groups, the rats in NC group (control) were fed with normal diet (10% fat and 0.5% salt ), and those in metabolic syndrome (MS) group with high fat diet (49% fat and 2% salt). The body weight, blood pressure, fasting blood glucose (FBG), blood lipid and fasting insulin level were serially measured. Such feedings were continued for 24 weeks, and then the intraperitoneal glucose tolerance test and hyperinsuline-euglycemic gomphosis test were performed, and carotid arterial pressure and visceral fat were measured. RT-PCR was used to detect the genes related to energy consumption, glucose-lipid metabolism in white adipose, brown adipose and muscle tissue. Results Compared with NC group, all the variables were increased significantly, such as body weight, visceral fat weight, blood pressure, serum levels of TG and FFA. A marked insulin-resistance and decreased glucose tolerance were found in MS group. Hyperinsuline-euglycemic gomphosis test revealed that the mRNA expression of 23 genes related to glucose-lipid and energy metabolism changed significantly in white adipose, brown adipose and muscle tissue in MS group as compared with NC group. Conclusion Prolonged high fat plus high salt diet may cause the clinical features of MS in rats. The changes in various genes may be involved in the mechanisms involved in the pathogenesis.