OBJECTIVE:To investigate the efficacy and underlying mechanisms of action of Kushen decoction on high-fatdiet-induced hyperlipidemia in rats using RNA-seq technology.METHODS:The efficacy of a Kushen decoction(苦参汤),...OBJECTIVE:To investigate the efficacy and underlying mechanisms of action of Kushen decoction on high-fatdiet-induced hyperlipidemia in rats using RNA-seq technology.METHODS:The efficacy of a Kushen decoction(苦参汤),at a concentration of 1 mL/g of crude medicine prepared according to the method commonly used in clinical practice,was investigated on 24 specific pathogen-free male Sprague-Dawley rats.Liver tissues were compared using RNA-Seq technology.The differentially expressed genes were further investigated by real-time fluorescent quantitative polymerase chain reaction(q PCR and Western blot(WB).RESULTS:Serum triglycerides(TG),liver low-density lipoprotein cholesterol(LDL-C),body weight,body length,and Lee’s index were significantly increased in the untreated hyperlipidemia-induced group(model)compared with the control group,whereas liver highdensity lipoprotein cholesterol(HDL-C)was significantly decreased.Serum TG,liver LDL-C,bodyweight,and Lee’s index were decreased in the high-dose Kushen decoction group(HDKS)compared with the model group,whereas liver HDL-C was significantly increased.Similarly,liver TG tended to decline in the HDKS group.Comparison of the gene expression profiles in the livers from different groups indicated that the Kushen decoction significantly affected metabolic pathways,PPAR signalling pathway,and circadian rhythm(Q≤0.05),with the genes ARNTL,PER3,and CLOCK being differentially expressed.qPCR and WB analysis confirmed the differential expression of the genes discovered by transcriptomics analysis.CONCLUSION:The Kushen decoction may achieve a lipid-lowering effect on hyperlipidemic rats by regulating metabolic pathways and the circadian rhythm pathway and in particular,their related genes ARNTL,PER3,and CLOCK.展开更多
基金Supported by National Natural Science Foundation of China(No.81760787)China Postdoctoral Science Foundation(No.2017M622101)+6 种基金Scientific Foundation of the Education Department of Jiangxi Province(No.GJJ190643)Traditional Chinese Medicine Scientific Research Subject of Jiangxi Province(No.2019A111,2019B110)Health and Family Planning Commission of Jiangxi Province(No.20195651,No.20203766,No.20203773,No.202131047 and No.202131054)Collaborative Innovation of Modern Science and Technology and Industrial Development of Jiangxi National Traditional Medicine(Gan Jiao Gao Zi,[2013]No.109)Jiangxi middle-aged and young backbone Talents Project of traditional Chinese medicine(Gan TCM Ke Jiao Zi[2021]No.2)the Specialized Research Fund for the First-Class Discipline of Chinese Herb from Jiangxi Province(No.JXSYLXK-ZHYAO111)Key Discipline Project of Jiangxi University of Chinese Medicine(No.2013jzzdxk069)
文摘OBJECTIVE:To investigate the efficacy and underlying mechanisms of action of Kushen decoction on high-fatdiet-induced hyperlipidemia in rats using RNA-seq technology.METHODS:The efficacy of a Kushen decoction(苦参汤),at a concentration of 1 mL/g of crude medicine prepared according to the method commonly used in clinical practice,was investigated on 24 specific pathogen-free male Sprague-Dawley rats.Liver tissues were compared using RNA-Seq technology.The differentially expressed genes were further investigated by real-time fluorescent quantitative polymerase chain reaction(q PCR and Western blot(WB).RESULTS:Serum triglycerides(TG),liver low-density lipoprotein cholesterol(LDL-C),body weight,body length,and Lee’s index were significantly increased in the untreated hyperlipidemia-induced group(model)compared with the control group,whereas liver highdensity lipoprotein cholesterol(HDL-C)was significantly decreased.Serum TG,liver LDL-C,bodyweight,and Lee’s index were decreased in the high-dose Kushen decoction group(HDKS)compared with the model group,whereas liver HDL-C was significantly increased.Similarly,liver TG tended to decline in the HDKS group.Comparison of the gene expression profiles in the livers from different groups indicated that the Kushen decoction significantly affected metabolic pathways,PPAR signalling pathway,and circadian rhythm(Q≤0.05),with the genes ARNTL,PER3,and CLOCK being differentially expressed.qPCR and WB analysis confirmed the differential expression of the genes discovered by transcriptomics analysis.CONCLUSION:The Kushen decoction may achieve a lipid-lowering effect on hyperlipidemic rats by regulating metabolic pathways and the circadian rhythm pathway and in particular,their related genes ARNTL,PER3,and CLOCK.
