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目的探讨11β-羟基类固醇脱氢酶1型(11β-HSD1)抑制剂BVT 2733对高脂血症大鼠肝脏、脂肪和骨骼肌脂代谢基因表达的影响。方法采用高脂饮食喂养建立高脂血症大鼠模型。将40只高脂血症大鼠随机分为模型组和BVT 2733(20 mg/kg)组,每组20只。另取20只普通饲料喂养的SD大鼠作对照组。分别观察BVT 2733对甘油三酯(TG)、总胆固醇(TC)、低密度脂蛋白(LDL-C)、高密度脂蛋白(HDL-C)水平的影响,并测定肝脏和肾周、大网膜及睾周脂肪组织脂肪含量,测定腓肠肌组织中Rev-erba、FAT/CD36、SCD1及CPT1 mRNA的表达水平。结果 BVT 2733治疗后,高脂血症大鼠的TG、TC和LDL-C明显低于模型组(P<0.05),并且肝脏和内脏脂肪的脂肪含量明显低于模型组(P<0.05),腓肠肌组织中Reverba mRNA水平明显低于模型组(P<0.05),FAT/CD36、SCD1及CPT1 mRNA水平明显高于模型组(P<0.05)。结论 BVT 2733可改善高脂血症大鼠的血脂及脂蛋白水平紊乱,降低肝脏脂肪含量并稳定骨骼肌脂代谢基因表达,提示抑制11β-HSD1活性对高脂血症相关的肝脏、脂肪组织和骨骼肌异常脂质代谢有一定改善作用。
Objective To investigate the effect of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) inhibitor BVT 2733 on lipid metabolic gene expression in liver, fat and skeletal muscle of hyperlipidemic rats. Methods Hyperlipidemia rats were established by feeding with high fat diet. Forty hyperlipidemic rats were randomly divided into model group and BVT 2733 (20 mg / kg) group, 20 rats in each group. Another 20 normal feed-fed SD rats as control group. The effects of BVT 2733 on triglyceride (TG), total cholesterol (TC), low density lipoprotein (LDL-C) and high density lipoprotein (HDL-C) Membrane and perihematomal adipose tissue were measured to determine the expression of Rev-erba, FAT / CD36, SCD1 and CPT1 mRNA in gastrocnemius tissue. Results After treatment with BVT 2733, TG, TC and LDL-C in hyperlipidemic rats were significantly lower than those in model group (P <0.05), and fat content in liver and visceral fat was significantly lower than those in model group (P <0.05) Reverba mRNA level in gastrocnemius muscle tissue was significantly lower than that in model group (P <0.05), and the levels of FAT / CD36, SCD1 and CPT1 mRNA in gastrocnemius muscle were significantly higher than those in model group (P <0.05). Conclusion BVT 2733 can ameliorate the disorder of lipid and lipoprotein in hyperlipidemic rats, decrease the fat content of liver and stabilize the expression of lipid metabolism genes in skeletal muscle, suggesting that inhibiting the activity of 11β-HSD1 may contribute to hyperlipidemia-related liver and adipose tissue and Skeletal muscle abnormal lipid metabolism has a certain effect.