Changes Of Expression Of The Zinc Transporter Zip2 In Ejection Fraction Preserved Heart Failure

Objective:Establish an animal model of HFpEF,measure the changes of zinc concentration and expression of Zip2 in rats with HFpEF,explore the critical role of zinc and Zip2 in HFpEF.Methods:We used DSS rats to establish the animal model of HFpEF.We randomly assigned DSS rats to experimental and control groups.The experimental group was fed with high-salt diet(8% sodium chloride)and the control group was fed by normal diet(0.3% sodium chloride).Except for sodium chloride concentration,the other feed components and feeding conditions were same.Observed the mental status and vital signs of each group of rats,blood pressure and heart rate were measured every two weeks,we measured the cardiac ultrasound parameters of rats at the age of 6 weeks,12 weeks,and 19 weeks.We obtained cardiac specimens of each groups rats and used ICPOES to determine the concentration of zinc of two groups.The expression of Zip2 mRNA and protein in the myocardial cells of two groups was detected by qPCR and Western blot.Results:At the age of 19 weeks,compared with the control group,the rats in the experimental group showed dull hair,burnout and decreased activity.At the same time,blood pressure of the experimental group was significantly higher than control group.At the age of 19 weeks,LVSd、LVDd、LVPWd、LVPWs、LVM and LVM/BW were significantly higher in the experimental group than control group.BW was lower compared with the control group.The results showed that the rats in the experimental group had normal systolic function with decreased diastolic function,showed symptoms of HFpEF.Measure the changes of zinc concentration and expression of Zip2 in rats with HFpEF,the concentration of zinc in experimental group was increased by 120% compared with the control group(P<0.05).indicating that the concentration of zinc in the myocardial tissue increased in HFpEF.In addition,compared with the control group.the expression of Zip2 mRNA and protein in the myocardial cells of the experimental group was decreased by 40% and 50%,respectively(P<0.05).The concentration of zinc in myocardial tissue increased in HFpEF,while the expression of Zip2 in cardiomyocytes decreased,which reduced the migration of extracellular zinc into cells to maintain zinc homeostasis.Conclusion:High salt-fed DSS rats can reach the HFpEF animal model index around the age of 19 weeks.This model can be used in the research of HFpEF.When HFpEF occur,the concentration of zinc in the cardiac tissue increased,and the expression of Zip2 mRNA and protein decreased to reduce the intracellular zinc concentration and maintain the zinc homeostasis to protect the myocardium.