Expression Of Micro RNA-146a And CXCR4 In Myocardial Tissue And Cardiac Fibroblasts Of Diabetic Cardiomyopathy

Objective:Diabetic complications are one of the most pressing health problems at present.Among many complications,diabetic cardiomyopathy（Diabeticcardiomyopathy,DCM）is the one with the highest incidence.Hyperglycemia can induce abnormal proliferation of cardiac fibroblasts（Cardiacfibroblasts,CFs）and deposition of extracellular matrix（Extracellularmatrix,ECM）to accelerate the process of myocardial fibrosis（Myocardialfibrosis,MF）,resulting in ventricular systolic and diastolic dysfunction.It is reported that microRNA-146a can inhibit hepatocyte interstitial transformation and slow down the process of liver fibrosis by regulating TGF-βsignaling pathway.Studies have shown that miR-146a aggravates lipopolysaccharide-induced inflammatory injury by targeting CXCR4 in articular chondrocytes.CXCR4 has been confirmed to be involved in the pathogenesis of myocardial fibrosis in diabetic cardiomyopathy.The purpose of this article is to establish animal and cell models to detect the expression of miR-146a and CXCR4 in the model,and to explore the role of miR-146a and CXCR4 in the process of myocardial fibrosis in diabetic cardiomyopathy.Methods:Animal experiment:After the rats were acclimate,the rats were set up into two groups randomly,one group had 20 animals,and the two groups were labeled respectively.In the model group,STZ was used for modeling.The injection method was single intraperitoneal injection,and the drug dose was controlled at 60mg/kg.A single intraperitoneal injection of the same amount of saline was also used in the control group.Three days and one week later,blood glucose concentration was measured by caudal vein blood collection to determine the modeling situation.When blood glucose concentration>16.7mmol/L was considered to be successful,routine feeding was conducted for 12 weeks after drug injection.The rats were killed after anesthesia,The pathological changes of myocardial tissue were observed by HE and Masson staining in paraffin section.The remaining myocardial tissue was further extracted RNA and protein,and the detection was performed by q RT-PCR and Westernblot methods.The detection objects were the relative expression of miR-146a and the target proteinsα-SMA,Col1A1 and CXCR4 in each group.Cell experiment:primary cardiac fibroblasts were cultured in high glucose medium(33.3mmol·L^-1)and low glucose medium(5mmol·L^-1)respectively.And use the same method to detect the relative expression and correlation of miR-146a in CFs.The expression of the target protein.MTT detects the changes of high glucose on the proliferation activity of CFs.Results:HE and Masson staining showed that collagen accumulation,cell disorder and inflammatory infiltration were significant in the model group.In the animal experiment,the expression of miR-146a in the model group was lower than that in the control group,but the target protein in the model group was higher.In cell experiment,the expression of miR-146a in high glucose group was lower than that in low glucose group,while the target protein in high glucose group was higher.After high glucose treatment,the CFs’proliferative activity was stimulated by the MTT assay.Conclusion:The expression of miR-146a in myocardium and fibroblasts of diabetic cardiomyopathy is inhibited,while the expression of CXCR4 is increased.It can be inferred that miR-146a may can regulate and contral the express of CXCR4.But the further research is needed in the later stage.