藿香对营养性肥胖大鼠降脂的作用及其代谢组学研究

Study on the lipid-lowering Effect and Mechanism of Musk on Nutritional Obese Rats

目的研究藿香干预营养性肥胖大鼠的降脂作用,分析其对营养性肥胖大鼠内源性物质的影响,寻找潜在的生物标志物分析代谢途径。方法SD大鼠,雄性,30只,按体重随机分为2组,正常组(10只)、造模组(20只),分别喂以普通饲料与高脂饲料,喂养4周,建立营养性肥胖大鼠模型;造模组按体重和血清TG含量随机分为模型组和藿香给药组。给药4周后,测量血清胆固醇(CHOL)、甘油三酯(TG)、高密度脂蛋白(HDL-C)、低密度脂蛋白(LDL-C)、葡萄糖(GLU)的含量。并利用高分辨质谱检测内源性代谢物信号,经分析主成分,筛选出潜在的生物标记物,应用MetPA数据库对差异化合物进行通路分析。结果造模4周大鼠体重、Lee􀆳s指数、TG、CHOL、HDL-C、LDL-C明显高于正常组(P<0.01),成功建立营养性肥胖大鼠模型。藿香给药干预4周,与模型组相比,藿香给药组血清中TG含量明显下降(P<0.01);血清代谢组学分析发现10种内源性差异化合物,主要通过氨酰基-tRNA、苯丙氨酸、酪氨酸和色氨酸生物合成,鞘脂代谢,酪氨酸代谢4种途径发挥作用。结论藿香明显降低营养性肥胖大鼠血清TG含量,结合代谢组学分析结果发现藿香可能是通过干预蛋白质、氨基酸合成,调节氨基酸和脂质代谢来发挥降脂“化湿”的作用。

Objective To study the lipid-lowering effect of musk in rats with nutritional obesity,analyze its effect on endogenous substances in rats with nutritional obesity,and find potential biomarkers to analyze metabolic pathways.Methods Sprague-Dawley rats,male,30,were randomly divided into 2 groups according to body weight.The normal group(10 rats)and the model group(20 rats)were fed with normal feed and high-fat diet for 4 weeks to establish nutrition.Sexual obese rat model;after successful modeling,the model was randomly divided into a model group according to body weight and serum triglyceride(TG)content,and a musk administration group(3 g/kg).After 4 weeks of administration,the serum levels of triglyceride(TG),cholesterol(CHOL),high-density lipoprotein(HDL-C),and lowdensity lipoprotein(LDL-C)glucose(GLU)were measured;The endogenous metabolite signal was detected by mass spectrometry,the potential biomarkers were screened by principal component,and the differential compounds were analyzed by MetPA database.Results The body weight,Lee􀆳s index,TG,CHOL,HDL-C and LDL-C of the rats at 4 weeks were significantly higher than those of the normal group(P<0.01),and the rat model of nutritional obesity was successfully established.Musk was administered for 4 weeks,and compared with the model group,the serum TG content in the musk administration group was significantly decreased(P<0.01);serum metabolomics analysis found 10 endogenous differential compounds,mainly through aminoacyl-tRNA biosynthesis,phenylalanine,tyrosine and tryptophan biosynthesis,sphingolipid metabolism,tyrosine metabolism play four roles.Conclusion Musk significantly reduced serum TG content in nutritional obese rats.Combined with metabolomics analysis,it was found that musk may play a role in lipid-lowering and“wetting”by interfering with protein,amino acid synthesis,regulating amino acid metabolism and lipid metabolism.