심근경색 실험동물 모델에서 Insulin-like growth factor system의 조절
Regulation of IGF System in Rats after Experimental Myocardial Infarction
2
조회
0
다운로드
1
인용
0
참고문헌
키워드
초록
Insulin-like growth (IGF) system은 여러 가지 다양한 심근질환과 연관성이 있는 것으로 알려져 있으나심근경색에서 IGF system의 변화에 대해서는 밝혀져 있지 않다. 따라서 본 연구에서는 흰쥐 심근경색 모델을활용하여 IGF system의 변동을 살펴보아 심근경색에서 IGF system의 역할을 규명해보고자 하였다. 60일령의 수컷 흰쥐 왼심장동맥을 결찰하여 심근경색 모델을 만들었고 개흉하여 sham 대조군을 삼았다. 실험군은 심근경색 유발 후 1, 3, 7, 14 및 30일에 희생시켰고 대조군은 가슴안을 열고 30일에 희생시켰다. 혈청과 심근내 IGF-I과 IGF-II 농도와 혈청내 IGF binding protein (IGFBP)-1, IGFBP-3 농도를 측정하였다. 심장동맥을 결찰한 실험군에서 평균 심근경색의 크기는 왼심실의 35.2~42.3%이었다. 혈청내 IGF-I의 농도는대조군과 비교하여 명확하게 감소하였으나 IGF-II 농도는 차이를 나타내지 않았다. 혈청내 IGFBP-1의 농도는심근경색 후 1일과 3일에 큰 폭으로 상승하였고 IGFBP-3는 전 실험군에서 유의성 있게 증가하였다. 심근경색실험동물에서 심근의 IGF-I의 농도는 대조군과 비교하여 명확하게 감소한 반면, IGF-II의 농도는 변화가 없었다. 이상의 결과는 심근경색시 IGF system의 변동이 있음을 확인하였고 심근경색 후 심장의 반응에서 IGF system이 중요한 작용이 있음을 알 수 있었다.
Abstract
Insulin-like growth factor system (IGF system) has been reported to be associated with the variety of disorders of myocardial function. However, the effect of myocardial infarction (MI) on the IGF system has not been fully described. Thus, the present study was to investigate in more detail the changes of IGF system in the male rat following myocardial infarction (MI). Ligation of the left coronary artery was performed in male Sprague-Dawley male rats at 60 days of age. Control rats were obtained sham-operated animals. MI rats were sacrificed at 1, 3, 7, 14, and 30 day after ligation of left anterior descending coronary artery. Control rats were sacrificed on 30 day after thoracotomy. Myocardial infarct size was assessed by planimetry and perimetry. Serum and heart concentrations of IGF-I and -II were determined by radioimmunoassay. Serum levels of IGF-binding protein (IGFBP)-1 and IGFBP-3 were analyzed with a twosite immunoradiometric assay. Mean infarct size was 35.2~42.3% of the left ventricle after coronary occlusion in experimental groups. Serum levels of IGF-I were markedly reduced, but the levels of IGF-II were not altered in MI rats compared with shamligated controls. Serum IGFBP-I levels in MI rats were significantly increased at 1 and 3 day compared with sham rats. The levels of serum IGFBP-3 were significantly higher in the ligated rats. IGF-I levels of the infarct/periinfarct area of the left ventricle were significantly decreased in rats with myocardial infarction, whereas the levels of IGF-II remained unchanged. These results demonstrate that the IGF system is altered in the myocardial infarction and suggest that the IGF system plays an important role in the response of the heart to myocardial infarction.
참고문헌 (33)
- Ahn DC, "Induction of myocardial infarcts of a predictable size and location by branch pattern probability-assisted coronary ligation in C57BL", 6 mice, 2003, pp.286, 1201~1207
- 김인식, "흰쥐 왼쪽관상동맥의 분지 양상에 관한 해부학적 연구", 대한수의학회지, 47(1), pp.7~17 (2007), 대한수의학회
- Anversa P, "Myocardial response to infarction in the rat", Am J Pathol, 118, pp.484~492 (1985)
- Baxter RC, "Insulin-like growth factor binding proteins in the human circulation", a review. Horm Res, 42, pp.140~144 (1994)
- Berfield AK, "Insulin-like growth factor I (IGF-I) induces unique effects in the cytoskeleton of cultured rat glomerular mesangial cells", J Histochem Cytochem, 45, pp.583~593 (1997)
- Bondanelli M, "Predictive value of circulating IGF-I levels in ischemic stroke outcome", J Clin Endocronol Metab, 91, pp.3928~3934 (2006)
- Colao A, "The GH-IGF-I axis and the cardiovascular system: clinical implications", Clin Endocrinol, 69, pp.347~358 (2008)
- Conti E, "Markedly reduced insulinlike growth factor-I in the acute phase of myocardial infarction", J Am Coll Cardiol, 38, pp.26~32 (2001)
- Daughaday WH, "Insulin-like growth factors I and II. Peptide messenger ribonucleic acid and gene structure serum, and tissue concentrations", Endor Rev, 10, pp.68~91 (1989)
- Dean R, "Localization of the insulin-like growth factor system in a rat model of heart failure induced by myocardial infarction", J Histochem Cytochem, 47, pp.649~659 (1999)
- Delafontaine P, "Insulin-like growth factor I and its binding proteins in the cardiovascular system", Cardiovas Res, 30, pp.825~834 (1995)
- Elgin RG, "An insulin-like growth factor binding protein enhances the biologic response to IGF-I", Proc Natl Acad Sci, 84, pp.3254~3258 (1987)
- Friberg L, "Growth hormone and insulin-like growth factor-I in acute myocardial infarction", Eur Heart J, 21, pp.1547~1554 (2000)
- Hearse DJ, "Experimental models for the study of cardiovascular function and disease", Pharmacol Res, 41, pp.597~603 (2000)
- Heemskerk VH, "Insulin-like growth factor system and growth hormone in immunity and inflammation", Cytokine Growth Factor Rev, 10, pp.5~14 (1999)
- Janssen JAMJL, "Serum total IGF-I, and IGFBP-1 levels in an elderly population", Anterioscler Thromb Vasc Biol, 18, pp.277~282 (1998)
- Jones JJ, "Insulin-like growth factors and their binding proteins: biological actions", Endocrinol Rev, 16, pp.3~34 (1995)
- Kluge A, "Coordinate expression of the insulin-like growth factor system after microembolisation in porcine heart", Cardiovascular Res, 33, pp.324~331 (1997)
- Kotlyar AA, "Insulin-like growth factor I and II preserve myocardial structure in postinfarct swine", Heart, 86, pp.693~700 (2001)
- Lee CY, "Comparisons of various acidic treatments of bovine serum on insulin-like growth factor-I immunoreactive and binding activity", J Endocrinol, 127, pp.139~148 (1990)
- Lee WL, "Changes of the insulin-like growth factor I system during acute myocardial infarction: Implications on left ventricular remodeling", J Clin Endocrinol Metab, 84, pp.1575~1581 (1999)
- Liu YH, "Chronic heart failure induced by coronary artery ligation in Lewis inbred rats", Am J Physiol, 272, pp.722~727 (1997)
- Matthews KG, "Changes in IGFs in cardiac tissue following myocardial infarction", J Endocrinol, 163, pp.433~445 (1999)
- Muders F, "Animal models of chronic heart failure", Pharmacol Res, 41, pp.606~612 (2000)
- Nahrendorf M, "Time course of right ventricular remodeling in rats with experimental myocardial infarction", Am J Physiol Heart Circ Physiol, 284, pp.241~248 (2003)
- Pfeffer JM, "Progressive ventricular remodeling in rat with myocardial infarction", Am J Physiol Heart Circ Physiol, 29, pp.1406~1414 (1991)
- Pfeffer MA, "Ventricular remodeling after myocardial infarction", Circulation, 81, pp.1161~1172 (1990)
- Pfeffer MA, "Myocardial infarct size and ventricular function in rats", Circ Res, 44(4), pp.503~512 (1979)
- Reeves I, "Agerelated serum levels of insulin-like growth factor-I, - II and IGF-binding protein-3 following myocardial infarction", Growth Horm IGF Res, 10, pp.78~84 (2000)
- Ren J, "Insulin-like growth factor I as a cardiac hormone: physiological and pathophysiological implications in heart disease", J Mol Cell Cardiol, 31, pp.2049~2061 (1999)
- Siminiak T, "Myocardial replacement therapy", Circulation, 108, pp.1167~1171 (2003)
- Vogt AM, "Insulin- like growth factor-II delays myocardial infarction in experimental coronary artery occlusion", Cardiovas Res, 33, pp.469~477 (1997)
- Yamaguchi H, "Impact of serum insulin-like growth factor-1 on early prognosis in acute myocardial infarction", Inter Med, 47, pp.819~825 (2008)