Improvement of chronic heart failure by dexamethasone is not associated with downregulation of leptin in rats

<正> Aim:To demonstrate the hypothesis that dexamethasone（Dex）could improvechronic heart failure（CHF）by inhibiting the downstream signaling transductionof leptin but had no influence on the upregulation of leptin and its receptor inmyocardium.Methods:CHF was induced by left coronary artery ligation for 6weeks.CHF rats were treated with Dex 50 mg.kg1.d1.Hemodynamics,histology,reactive oxygen species（ROS）-related parameters,and leptin concentrations inserum were measured.The mRNA expression of matrix metalloproteinases（MMP）2/9,tissue inhibitor of metalloproteinases（TIMP）1/2,tumor necrosis factor（TNF）-α,and OB-Rb were measured by RT-PCR.Results:In the CHF rats,hemodynamicfunctions were deteriorated,which was accompanied with myocardium remodel-ing and histological changes.CHF rats showed hyperleptinemia and excessiveROS in the serum,and the upregulation of MMP-2/9,TNF-α,and leptin receptormRNA and downregulation of TIMP-1/2 mRNA in the myocardium compared withthe sham operation group.Dex treatment significantly ameliorated CHF in asso-ciation with the reversion of the abnormalities of MMP-2/9,TIMP-1/2,TNF-αandROS.But Dex had no influence on the hyperleptinemia and the upregulated leptinand its receptor in the myocardium during CHF.Conclusion:Dex improves CHFby inhibiting TNF-α,MMP-2,MMP-9,and ROS.Dex had no effects on upregulatedleptin and its receptor expression and hyperleptinemia induced by CHF.