Mechanism of Qingrun Formula in Improving Hepatic Insulin Resistance of Rats with Type 2 Diabetes Mellitus Based on High-throughput Sequencing
Objective:To explore the mechanism of Qingrun Formula in improving hepatic insulin resistance in rats with type 2 di-abetes mellitus(T2DM)through high-throughput RNA sequencing(RNA-seq).Methods:A T2DM model of rats was established by feeding rats a high-fat diet combined with intraperitoneal injection of streptozotocin(STZ).The successfully modeled rats were ran-domly divided into the model group,metformin group(150 mg/kg),and high-dose(11.2 g/kg),medium-dose(5.6 g/kg),and low-dose(2.8 g/kg)groups of Qingrun Formula,and a normal control group was set up.The rats were given intragastric intervention for eight weeks.Changes in fasting blood glucose(FBG),insulin resistance index(IRI),and insulin sensitivity index(ISI)were ob-served among the groups.RNA-seq technology combined with bioinformatics analysis was used to screen differentially expressed long-chain non-coding RNA(lncRNA),micro RNA(miRNA),and messenger RNA(mRNA).Gene ontology(GO)and Kyoto ency-clopedia of genes and genomes(KEGG)enrichment analyses and qPCR verification of differentially expressed genes were per-formed,and regulatory networks of competitive endogenous RNA(ceRNA)were constructed.Results:Compared with that in the model group,the FBG in the high-dose group of Qingrun Formula decreased significantly in the 6th and 8th week of intervention(P＜0.05).In the 8 th week of intervention,the IRI in all groups of Qingrun Formula decreased significantly(P＜0.01),while that in the high-dose and low-dose groups of Qingrun Formula increased significantly(P＜0.01,P＜0.05).85 key mRNA,12 miRNA,and 37 lncRNA were obtained through differential expression screening.12 core genes were obtained by protein-protein interaction(PPI)network,and the network of lncRNA-miRNA-mRNA was constructed.KEGG enrichment analysis revealed that differentially expressed genes were mainly involved in pathways such as JAK-STAT,PPAR,amino acid metabolism,and lipid metabolism.Con-clusion:Qingrun Formula may improve hepatic insulin resistance of rats with T2DM by regulating CYP2 and Acer2 genes through the lncRNA-miRNA-mRNA network and affecting Lpin1 and Insig1 genes,as well as PPAR,JAK-STAT,amino acid metabolism,lipid metabolism,and other signaling pathways.
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