[The antagonistic effect of PI3K-gamma inhibitor AS605240 on cardiac hypertrophy and cardiac fibrosis induced by isoproterenol in rats].

Abstract

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.

• Authors: Li-Fang Song, Wei Jiang, Yong Qing, Xiao-Hong Hu, Yi Li, Qing-Yi Tong, Xiao-Hua Wu
• Journal: Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition (Sichuan Da Xue Xue Bao Yi Xue Ban) Vol. 42 Issue 4 Pg. 471-4 (Jul 2011) ISSN: 1672-173X [Print] China
• PMID: 21866628 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 5-quinoxalin-6-ylmethylenethiazolidine-2,4-dione
• PSMF1 protein, human
• Proteins
• Quinoxalines
• Thiazolidinediones
• Proteasome Endopeptidase Complex
• Isoproterenol

Topics

• Animals
• Cardiomegaly (chemically induced, drug therapy)
• Fibrosis (chemically induced, drug therapy)
• Isoproterenol (pharmacology)
• Male
• Myocardium (pathology)
• Proteasome Endopeptidase Complex
• Proteins (antagonists & inhibitors)
• Quinoxalines (pharmacology, therapeutic use)
• Random Allocation
• Rats
• Rats, Wistar
• Thiazolidinediones (pharmacology, therapeutic use)