目的糖皮质激素在肥胖及胰岛素抵抗发病机制中起着至关重要的作用。该研究旨在探讨长期抑制糖皮质激素活性对肥胖及胰岛素抵抗的防治作用。方法采用4周龄雄性SD大鼠为动物模型,在给于高脂饲料喂养的同时,予含11β-羟甾类脱氢酶(11β-hydroxysteroid dehydrogenase,11β-HSD)抑制剂(glycyrrhetic acid,GE)800mg/L的水长期饮用至24周,并以单纯高脂饲料喂养组作为对照组,监测两组大鼠食物摄入量及体重变化。在GE应用24周后,进行口服葡萄糖耐量试验,并采用放射免疫方法检测血浆糖皮质激素、瘦素及胰岛素的水平,采用全自动生化分析仪检测血清胆固醇及甘油三脂的含量。结果随着GE治疗时间的延长,大鼠的食物摄入量较对照组逐渐减少,至6周时达到统计学意义,同时伴有相应的体重增长减慢,至8周时,GE组体重明显低于对照组。治疗24周时,血浆糖皮质激素水平较对照组无明显降低,但血浆瘦素及胰岛素水平均明显低于对照组;血清胆固醇及甘油三脂的含量也明显低于对照组;口服葡萄糖耐量试验结果显示GE组在15,30,60和120分钟时的血糖水平明显低于对照组。结论长期应用11β-羟甾类脱氢酶抑制剂能够抵抗高脂饮食诱导的肥胖及胰岛素抵抗。 Purpose Glucocorticoids play a crucial role in the pathogenesis of obesity and insulin resistance. This study aimed to investigate the long-term inhibition of glucocorticoid activity on the prevention and treatment of obesity and insulin resistance. Methods Four-week-old male Sprague-Dawley rats were used as experimental animal models. When fed with high-fat diet, 11β-hydroxysteroid dehydrogenase (11β-HSD) inhibitor (glycyrrhetic acid, GE ) 800mg / L of water for 24 weeks, long-term drinking and high fat-fed group as a control group to monitor the food intake and body weight changes in both groups. Twenty-four weeks after the application of GE, oral glucose tolerance test was carried out. Plasma glucocorticoid, leptin and insulin levels were measured by radioimmunoassay. Serum cholesterol and triglyceride were detected by automatic biochemical analyzer. Results With the prolongation of GE treatment, the food intake of rats decreased gradually compared with that of the control group, reaching statistical significance by 6 weeks, accompanied by the corresponding slowing of body weight gain. At 8 weeks, the body weight of GE group was significantly higher Lower than the control group. At 24 weeks of treatment, plasma glucocorticoid level was not significantly lower than that of the control group, but plasma leptin and insulin levels were significantly lower than the control group; serum cholesterol and triglyceride levels were significantly lower than the control group; oral glucose tolerance test The results showed that the blood glucose levels at 15, 30, 60 and 120 minutes in GE group were significantly lower than those in control group. Conclusion Long-term application of 11β-hydroxysteroid dehydrogenase inhibitors can resist the obesity and insulin resistance induced by high-fat diet.