红曲茯苓片对脾虚湿盛型高脂血症大鼠调节作用的血清代谢组学研究  

Serum metabolomics study on the regulation of Hongqu Fuling tablets on hyperlipidemia rats with spleen deficiency and damp-excess

作　　者：林涛 李婷婷 齐梦飞 尚上 向亚津晶 沈家燕 童瑛 刘葭[1] 吴清[1] LIN Tao;LI Ting-ting;QI Meng-fei;SHANG Shang;XIANG Ya-jin-jing;SHEN Jia-yan;TONG Ying;LIU Jia;WU Qing(School of Chinese Materia Medica,Beijing University of Chinese Medicine,Beijing 102488)

机构地区：[1]北京中医药大学中药学院,北京102488

出　　处：《中南药学》2024年第9期2266-2274,共9页Central South Pharmacy

基　　金：国家重点研发计划中医药现代化重点专项(No.2018YFC1706800)。

摘　　要：目的采用血清代谢组学探讨红曲茯苓片对脾虚湿盛型高脂血症大鼠血脂的调节作用机制。方法将SD大鼠随机分为空白组和造模组,造模组采用高脂饲料喂养,节制饮食并每日负重游泳进行脾虚湿盛型高脂血症造模,造模4周后将造模组分为模型组、红曲茯苓片组、血脂康组、阿托伐他汀组,分别予以红曲茯苓片混悬液[0.5g/(kg·d)]、血脂康混悬液[0.12g/(kg·d)]、阿托伐他汀钙片混悬液[0.12 g/(kg·d)]灌胃,6周后检测各组大鼠血清总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、血清胃动素(MTL)、D-木糖、醛固酮(ALD)和白蛋白(ALB)含量;肝脏组织染色切片观察病理变化;UPLC-MS法分析大鼠血清样本,采用非靶向代谢组学技术探究红曲茯苓片对脾虚湿盛型高脂血症大鼠体内代谢物的影响。结果与空白组相比,模型组大鼠血清TC、TG、LDL-C、ALD含量显著升高(P<0.001),血清MTL、D-木糖、ALB、HDL-C含量显著降低(P<0.05或P<0.001);与模型组比较,除阿托伐他汀组的LDL-C外,红曲茯苓片组、血脂康组以及阿托伐他汀组的其他指标含量均显著回调(P<0.05或P<0.01或P<0.001);代谢组学分析鉴定和筛选出106个差异代谢物,代谢通路主要涉及甘油磷脂代谢,鞘脂类代谢,苯丙氨酸、酪氨酸和色氨酸的生物合成,丙氨酸、天冬氨酸、谷氨酸代谢,D-谷氨酰胺和D-谷氨酸代谢等脂质和氨基酸代谢。结论红曲茯苓片对脾虚湿盛型高脂血症大鼠的血脂调节作用可能与其调节甘油磷脂代谢,鞘脂类代谢,苯丙氨酸、酪氨酸和色氨酸的生物合成,丙氨酸、天冬氨酸和谷氨酸代谢,D-谷氨酰胺和D-谷氨酸代谢等通路有关。Objective To determine the effect of Hongqu Fuling tablets on the regulation of blood lipid in hyperlipidemia rats with spleen deficiency and damp-excess.Methods SD rats were randomly divided into a blank group and a modeling group.The modeling rats were fed with high-fat diet and daily exhausting swimming combined with weight diet control to establish the model of spleen deficiency and damp-excess hyperlipidemia.Four weeks after modeling,the rats in the modeling group were divided into a model group,a Hongqu Fuling tablets group,a Xuezhikang group and an atorvastatin group.Hongqu Fuling tablets suspension[0.5 g/(kg·d)],Xuezhikang suspension[0.12 g/(kg·d)]and atorvastatin calcium tablets suspension[0.12 g/(kg·d)]were given for six weeks,respectively.The content of serum total cholesterol(TC),triglyceride(TG),low density lipoprotein cholesterol(LDL-C),high density lipoprotein cholesterol(HDL-C),motilin(MTL),D-xylose,aldosterone(ALD)and albumin(ALB)in each group was detected.The pathological changes in the liver tissue were observed in stained section.The serum samples of rats were analyzed by UPLC-MS,and the effects of Hongqu Fuling tablets on metabolites in rats with hyperlipidemia due to spleen deficiency and dampn-excess were determined by non-targeted metabolomics.Results Compared with the blank group,the serum TC,TG,LDL-C and ALD in the model group were significantly increased(P<0.001),while the serum MTL,D-xylose,ALB,and HDL-C were significantly decreased(P<0.05 or P<0.001).Compared with the model group,except for LDL-C in the atorvastatin group,the contents of all other indexes in Hongqu Fuling tablets group,Xuezhikang group and atorvastatin group all were callbacked significantly(P<0.05 or P<0.01 or P<0.001).Totally 106 different metabolites were screened and identified by metabolomics analysis.Metabolic pathways mainly involved glycerophospholipid metabolism,sphingolipid metabolism,biosynthesis of phenylalanine,tyrosine and tryptophan,metabolism of alanine,aspartic acid and glutamate,D-glutamine and D-

关 键 词：红曲茯苓片 高脂血症 代谢组学 脾虚湿盛 

分 类 号：R285[医药卫生—中药学]