Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2011
[The antagonistic effect of PI3K-gamma inhibitor AS605240 on cardiac hypertrophy and cardiac fibrosis induced by isoproterenol in rats].
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Song Li-Fang, Jiang Wei, Qing Yong, Hu Xiao-Hong, Li Yi, Tong Qing-Yi, Wu Xiao-Hua
Аннотация
OBJECTIVE: To investigate the therapeutic effect of PI3Kgamma 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 x 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 (P < 0.05) with a increased collagen inter cardiac muscle cells (P < 0. 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 (P < 0.05).
CONCLUSION: AS605240 may be an effective antagonist for cardiac hypertrophy and cardiac fibrosis.
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 x 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 (P < 0.05) with a increased collagen inter cardiac muscle cells (P < 0. 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 (P < 0.05).
CONCLUSION: AS605240 may be an effective antagonist for cardiac hypertrophy and cardiac fibrosis.