The Antagonistic Effect of PI3K-gamma Inhibitor AS605240 on Cardiac Hypertrophy and Cardiac Fibrosis Induced by Isoproterenol In Rats

Objective To investigate the therapeutic effect of PI3Kγ inhibitor AS605240 on cardiac hypertrophy and cardiac fibrosis induced by Isoproterenol in rats.Methods Wistar rats were randomly divided into three groups(n=10),control group,ISO group(vehicle group) and AS605240 group.The rats in control group without any treatment.The rats in ISO and AS605240 group were given ISO 10 mg/kg for 3 days and 5 mg/kg for another 11 days by subcutaneous injection to prepare the animal model of cardiac fibrosis.Rats in AS605240 group were given AS605240 50 mg/(kg·d) by intraperitoneal injection continuously for 14 days.The vehicle group received the intraperitoneal injection of an equal volume of 0.5% carboxymethylcellulose.Twenty-four hours after the last treatment,rats were sacrificed.Heart,body weight,cardiac function and the CVF were measured.Results Compared with the control group,the HW/BW of ISO group was increased significantly(P0.05) with a increased collagen inter cardiac muscle cells(P0.05).Compared with ISO group, histological examination of the heart showed that AS605240 significantly relieved the rat cardiac fibrosis and reduced heart/body weight ratios in experimental cardiac fibrosis(P0.05).Conclsuion AS605240 may be an effective antagonist for cardiac hypertrophy and cardiac fibrosis.