文章摘要
尹立平,王 龙,吕 珊,钟 毅,丁国宪,刘 娟.11β⁃HSD1抑制剂BVT.2733对肥胖小鼠多器官组织代谢与炎症相关基因表达的影响[J].南京医科大学学报,2019,(12):1716~1722
11β⁃HSD1抑制剂BVT.2733对肥胖小鼠多器官组织代谢与炎症相关基因表达的影响
Effects of 11β⁃HSD1 inhibitor—BVT.2733 on the expressions of specific genes related to metabolism and inflammation of multiple organs in obese mice
投稿时间:2019-06-27  
DOI:10.7655/NYDXBNS20191203
中文关键词: BVT.2733  11β⁃HSD1  能量代谢  炎症
英文关键词: BVT.2733  11β⁃hydroxysteroid dehydrogenase type 1  energy metabolism  inflammation
基金项目:国家自然科学基金面上项目(81570773,81871106)
作者单位
尹立平 南京医科大学第一附属医院老年内分泌科江苏 南京 210029 
王 龙 南京医科大学第一附属医院老年内分泌科江苏 南京 210029 
吕 珊 南京医科大学第一附属医院老年内分泌科江苏 南京 210029 
钟 毅 中国药科大学药化教研室江苏 南京 210009 
丁国宪 南京医科大学第一附属医院老年内分泌科江苏 南京 210029 
刘 娟 南京医科大学第一附属医院老年内分泌科江苏 南京 210029 
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中文摘要:
      目的:评估11β?羟基类固醇脱氢酶1(11β?hydroxysteroid dehydrogenase type 1,11β?HSD1)抑制剂BVT.2733对肥胖小鼠骨骼肌、肝脏、肾脏、心肌和脾脏中代谢和炎症相关基因表达的影响。方法:构建高脂饮食诱导的肥胖小鼠模型,分为正常饮食组、高脂饮食组和高脂饮食+BVT.2733处理组。采用RT?PCR检测骨骼肌、心肌、肝脏、肾脏和脾脏中的代谢及炎症相关基因的表达。结果:在代谢方面,BVT.2733可促进骨骼肌和心肌的代谢指标UCP2和GLUT4的表达,同时,BVT.2733可抑制肝脏的脂质合成关键酶SREBP和FAS的表达,并可以使肾脏的葡萄糖重吸收蛋白SGLT1和SGLT2表达降低。在炎症方面,BVT.2733可显著抑制脾脏的IFN?γ、IL?13、IL?4和IL?5的表达,同时可减少骨骼肌和心肌炎症因子的表达。结论:BVT.2733对肥胖小鼠的骨骼肌、肝脏、肾脏、心肌和脾脏的代谢及炎症相关基因的表达有显著影响。
英文摘要:
      Objective:This study aims to to assess the effect of BVT.2733,a selective 11β?hydroxysteroid dehydrogenase type 1 inhibitor,on energy metabolism and inflammation?related gene expression in hepatic,skeletal muscular,cardiac muscular,renal and splenic tissues in C57BL/6J mice. Methods:C57BL/6J mice were fed at a normal fat diet(NC)or high fat diet(HFD). HFD treated mice were then administrated with BVT.2733(HFD+BVT)or vehicle(HFD). We examined the effects of BVT.2733 on energy metabolism?related genes and typical inflammatory genes expression in hepatic,skeletal muscular,cardiac muscular,and renal tissues by RT?PCR. Results:The expression of glucose consumption?related genes such as UCP2 and GLUT4 increased significantly,while mRNA level of PDK2 and PDK4,as the negative regulator of glucose oxidation,increased significantly in the skeletal and cardiac muscle of HFD+BVT mice. In liver,11β?HSD1 inhibitor significantly reduced the key genes expression of lipid synthesis,including SREBP and FAS. Interestingly,11β?HSD1 inhibitor also significantly inhibited the critical glucose reabsorption genes expression of SGLT1 and SGLT2 in kidney. On the other hand,there was significant inhibition of the typical inflammatory gene,such as TNF?α,MCP1,IL?6 and IL?5,both in skeletal and cardiac muscles. Conclusion:BVT.2733 had a remarkable effect on the expressions of specific genes related to metabolism and inflammation in skeletal muscular,cardiac,hepatic,renal and splenic tissues in obese mice.
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