目的 11β-羟基类固醇脱氢酶1型(11β-HSD1)、促酰化蛋白(ASP)在肥胖伴高脂血症中的机制。方法随机选取SD雄性大鼠60只,均分为实验组和对照组,实验组施以高脂饮食,对照组常规饮食,观察1~8 w进食量、体重和血压的变化;并在8 w后检测甘油三酯(TG)、总胆固醇(TC)、低密度脂蛋白(LDL)、极低密度脂蛋白(VLDL)、高密度脂蛋白(HDL)水平。处死动物取其肝脏,利用RT-PCR方法测量组织中11β-HSD1、脂蛋白酯酶(LPL)mRNA的变化,利用转染技术转染11β-HSD1 RNAi后3T3-L1脂肪细胞并与不同浓度ASP培养,以正常脂肪细胞作为对照,观察细胞凋亡和细胞活性。结果实验组食量先下降后上升,而对照组逐渐下降;实验组体重急剧上升,且大于对照组;实验组血压逐渐上升,而对照组维持一定水平;在第8周,实验组血脂水平显著高于对照组;实验组11β-HSD1 mRNA水平大于对照组,而LPL mRNA水平则相反;随着ASP溶液浓度的升高,未转染11β-HSD1 RNAi后3T3-L1脂肪细胞活力逐渐上升。而转染11β-HSD1 RNAi后3T3-L1脂肪细胞活力不变,而细胞凋亡与此相反。结论11β-HSD1是导致高脂血症和肥胖的一个有效因素,ASP通过11β-HSD1基因片段对脂肪细胞进行调节,从而影响脂类代谢。 OBJECTIVE: To investigate the mechanism of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) and pro-acylation protein (ASP) in obesity with hyperlipidemia. Methods Sixty male Sprague Dawley rats were randomly divided into experimental group and control group. The experimental group was given high-fat diet, and the control group was given routine diet. The changes of food intake, body weight and blood pressure were observed from 1 to 8 weeks. The triglyceride (TG), total cholesterol (TC), low density lipoprotein (LDL), very low density lipoprotein (VLDL) and high density lipoprotein (HDL) were detected. The animals were sacrificed and their livers were harvested. The changes of 11β-HSD1 and lipoprotein lipase (LPL) mRNA in the tissues were measured by RT-PCR. The 3T3-L1 adipocytes were transfected with 11β-HSD1 RNAi and transfected with different concentrations of ASP The normal adipocytes were used as a control to observe the apoptosis and cell activity. Results The food intake of the experimental group decreased first and then increased while that of the control group decreased gradually. The body weight of the experimental group increased sharply and was greater than that of the control group. The blood pressure of the experimental group increased gradually while the control group maintained a certain level. At the 8th week, In the control group, the level of 11β-HSD1 mRNA in the experimental group was higher than that in the control group, while the level of LPL mRNA was opposite. With the increase of ASP concentration, the viability of 3T3-L1 adipocytes increased gradually after transfected with 11β-HSD1 RNAi. However, the viability of 3T3-L1 adipocytes was unchanged after transfection with 11β-HSD1 RNAi, while the apoptosis was opposite. Conclusion 11β-HSD1 is an effective factor leading to hyperlipidemia and obesity. ASP modulates adipocytes through the 11β-HSD1 gene fragment and thus affects lipid metabolism.