Prediction Of MiRNA Treatment Target In Essential Hypertension With Type 2 Diabetes Mellitus

Objective:Explore the pathogenesis of essential hypertension(EH)combined with type 2 diabetes mellitus(T2DM),predict the therapeutic target of miRNA in EH combined with T2DM,and explore the potential value of miRNA in clinical treatment.Methods:Including 80 patients in the geriatrics and diabetes department of the First Affiliated Hospital of Kunming Medical University from January to June 2019,divided into EH group,T2DM group,EH+T2DM group and normal control(NC)group,20 cases in each group.The clinical data and plasma of patients were collected,and the expression levels of miR-27a-5p,miR-130a-5p,miR-195-5p,and miR-197-5p in the plasma of four groups of patients were detected by RT-qPCR,and the target gene of miRNA was predicted using bioinformatics software.The dual luciferase reporter gene was used to detect the miRNA targeting effect on the target gene,and the data was statistically analyzed using SPSS 23.0 software.Results:1.There was no significant difference in clinical indicators between patients in EH group and NC group(P>0.05);SUA and FPG in T2DM group was higher than those in NC group,the difference was statistically significant(P<0.05);LDL-C in EH+T2DM group was lower than the NC group,the difference was statistically significan,FPG was higher than the NC groupt(P<0.05),there was no significant difference in smoking history,BMI,TC,TG,HDL-C,Scr,SUA,BUN(P>0.05).2.RT-qPCR results showed that compared with NC group,miR-27a-5p,miR-130a-5p,miR-195-5p and miR-197-5p expression levels of EH group,T2DM group,EH+T2DM group were all different degrees of down-regulation,in which the relative expression of miR-27a-5p in T2DM group and NC group was statistically significant(P=0.038),the relative expression of miR-130a-5p in EH group and NC group was statistical significance(P=0.021),the relative expression of miR-195-5p in EH+T2DM group and NC group was statistically significant(P=0.027),the relative expression of miR-19 7-5p was no significant difference between the EH group,T2DM group,EH+T2DM group and NC group(P>0.05).3.Bioinformatics software predicts that DRD1 may be the target gene of miR-195-5p.Dual luciferase reporter gene detection showed that over-expressed miR-195-5p can significantly inhibit the fluorescent activity of DRD1 3'UTR,when the seed sequence at the binding site of DRD1 3'UTR and miR-195-5p was mutated,this inhibition disappeared.Conclusions:1.The decrease of LDL-C level and the increase of FPG level are related to the incidence of EH combined with T2DM,and are risk factors for the development of EH combined with T2DM.2.miR-195-5p is significantly down-regulated in the plasma of patients with EH combined with T2DM.DRD1 is a target gene of miR-195-5p.miR-195-5p may directly target DRD1 and participate in the development of EH combined with T2DM.It may become a biomarker of EH combined with T2DM,and may become a new target for the treatment of EH combined with T2DM and its complications.