Korean Circ J.  2002 Dec;32(12):1116-1123. 10.4070/kcj.2002.32.12.1116.

Cardioprotective Effect of IGF-1 in Mouse with Adriamycin Induced Cardiomyopathy

• Park CS
• Youn HJ
• Cho EJ
• Oh YS
• Baek SH
• Lee JH
• Kang JH
• Chung WS
• Chae JS
• Kim JH
• Choi KB
• Hong SJ

• KMID: 1858736
• DOI: http://doi.org/10.4070/kcj.2002.32.12.1116

Abstract

BACKGROUND AND OBJECTIVES: The purpose of this study was to investigate the apoptotic pathway, and the effect and mechanism of IGF-1 (insulin like growth factor 1) as a therapeutic agent, in Adriamycin (ADR) induced cardiomyopathy.
MATERIALS AND METHODS
We divided 17 mice into ADR (n=6), ADR +IGF-1 (n=6) and saline (n=5) groups. The following were injected into the intraperitoneal cavity for the specified periods: 2.5 mg/kg of ADR every week for 6 weeks, 0.1 mg/kg of IGF-1 in the 5th and 6th weeks and 10 mL/kg of saline every week for 6 weeks. Transthoracic echocardiography, with a 15MHz linear array, was performed before and after injection of the drugs. A TUNEL assay and immunohistochemical staining for Bax, bcl-2, capase-8 and 9, and western blotting for Bax and bcl-2 were performed on the myocardium.
RESULTS
The fractional shortening decreased (38.5+/-3.2% before vs. 29.2+/-5.5% after, p<0.05) and the left ventricular end systolic dimension increased (2.5+/-0.3 mm before vs. 3.1+/-0.5 mm after, p<0.05) following the injection of the ADR, but there were no interval changes in the mice treated with saline or ADR+IGF-1. The TUNEL assay showed a higher apoptotic index in the mice treated with ADR than in those treated with saline or ADR+IGF-1 (46+/-8% in ADR, 0.1+/-0.03% in control, 22+/-5% in ADR+IGF-1, p<0.05). The immunohistochemical staining and western blot showed an increase in the expression of Bax, and a decrease in the expression of bcl-2 in the mice treated with ADR than in those treated with ADR+IGF-1 or saline.
CONCLUSION
The apoptosis caused by the increased expression of Bax, and the decreased expression of bcl-2, was an important pathogenetic mechanism, and the IGF-1 prevents the progression of cardiomyopathy by attenuating the expressions of Bax and bcl-2 in ADR induced cardiomyopaththy.

Keyword

Doxorubicin; Cardiomyopathy, congestive; Apoptosis; Insulin-like growth factor I

MeSH Terms

Animals
Apoptosis
Blotting, Western
Cardiomyopathies*
Cardiomyopathy, Dilated
Doxorubicin*
Echocardiography
In Situ Nick-End Labeling
Insulin-Like Growth Factor I*
Mice*
Myocardium
Doxorubicin
Insulin-Like Growth Factor I