摘要
目的研究血管紧张素Ⅱ受体拮抗剂(angiotensinⅡreceptor blocker,ARB)对小鼠能量代谢的影响及可能机制。方法①选用雄性6周龄C57BL/6N小鼠,分别以普通饲料(normal diet,ND)、高脂饲料(high-fat diet,HFD)喂养6周,诱导糖尿病肥胖小鼠,测定小鼠体质量、空腹血糖;②将高脂饮食诱导的糖尿病肥胖小鼠采用数字表法随机分为对照组(control,Con)、药物处理组(ARB),分别以每日3 mg/kg的0.9%(质量分数)氯化钠注射液(以下简称生理盐水)和缬沙坦灌胃处理6周后进行小鼠体质量、体温测定、葡萄糖耐量实验、呼吸代谢检测、脂肪组织苏木精-伊红染色(hematoxylin-eosin,HE)及棕色脂肪组织产热相关基因表达情况检测;③以雄性6周龄Leptin receptor基因敲除的糖尿病肥胖小鼠模型(db/db小鼠)为实验对象,同样分别以每日3 mg/kg的生理盐水和缬沙坦灌胃处理5周后进行小鼠体质量、空腹血糖及体温测定。结果高脂饮食成功诱导了糖尿病肥胖小鼠(HFD小鼠)模型,缬沙坦灌胃处理能显著降低HFD小鼠体质量增长率及db/db小鼠体质量。在HFD小鼠中,缬沙坦增加4℃冷处理环境中HFD小鼠体温,提高HFD小鼠能量消耗,但对HFD小鼠糖代谢无明显改善作用。在db/db小鼠中,与对照组相比,缬沙坦处理后db/db小鼠空腹血糖明显降低,4℃冷处理2 h和3 h体温有上升趋势,但差异无统计学意义。此外,在HFD小鼠中,缬沙坦处理使棕色脂肪组织(brown adipose tissue,BAT)、皮下脂肪组织(subcutaneous adipose tissue,SUB)以及性腺旁脂肪组织(epididymal adipose tissue,EP)细胞体积明显减小,并且在mRNA水平,缬沙坦促进了BAT中UCP1的表达,Prdm16、PGC1α、AP2表达无明显改变。结论缬沙坦可改善肥胖小鼠能量代谢,其机制可能与ARB对BAT产热功能的促进作用有关。
Objective To study the effect and possible mechanism of angiotensinⅡreceptor blocker(ARB)on energy metabolism in mice.Methods①Male 6-week-old C57BL/6N mice were fed with normal diet(ND)and high-fat diet(HFD)for 6 weeks,then detect their body weight and fasting blood glucose.②The diabetic mice induced by high-fat diet were randomly divided into control group(Con)and drug treatment group(ARB).They were administered with saline and valsartan at a dose of 3 mg/kg per day via gastric lavage for 6 weeks.After that,the body weight,body temperature,intraperitoneal glucose tolerance test,respiratory metabolism rate,hematoxylin-eosin staining of adipose tissue,and the expression of thermogenesis-related genes in brown adipose tissue were examined.③By using male 6-week-old db/db mice as the experimental subjects,they were also administered with saline and valsartan at a dose of 3 mg/kg per day via gastric lavage for 5 weeks.After that,the body weight,fasting blood glucose,and body temperature were measured.Results High-fat diet successfully induced the diabetic mouse model.Valsartan treatment significantly reduced the weight gain rate of HFD mice and the body weight of db/db mice,increased the body temperature of HFD mice in a 4℃cold environment,and improved the energy expenditure of HFD mice,but had no significant improvement on glucose metabolism in HFD mice.Compared with the control group,the fasting blood glucose level of db/db mice was significantly reduced after valsartan treatment,and the body temperature showed an upward trend after 2 h and 3 h of cold treatment at 4℃,but the difference was not statistically significant.In addition,for HFD mice,valsartan treatment significantly reduced the cell volume of brown adipocyte,subcutaneous adipocyte,and epididymal adipocyte.At the mRNA level,valsartan promoted the expression of UCP1 in brown adipose tissue,while the expression of Prdm16,PGC1α and AP2 expression did not change significantly.Conclusions Valsartan can improve energy metabolism in obese mice,and its mechanism may be related to the positive effects of ARB on the thermogenesis of brown adipose tissue.
作者
纪文怡
宋丽妮
曹曦
Ji Wenyi;Song Lini;Cao Xi(Beijing Diabetes Institute,Beijing 100730,China;Department of Endocrinology,Beijing Tongren Hospital,Capital Medical University,Beijing 100730,China)
出处
《首都医科大学学报》
北大核心
2025年第1期106-114,共9页
Journal of Capital Medical University
基金
国家自然科学基金项目(82270897,82070850)
北京市自然科学基金项目(7242181,7244311)。
