| 임상현, 장기육, 김희열, 윤호중, 백상홍, 승기배, 김재형, 홍순조, 최규보 |
Backgroud : Myocardial fibrosis plays an important role in development of the diabetic cardiomyopathy. Advanced glycosylation end products (AGEs) is recognized as important mediators of myocardial fibrosis in diabetes, via receptor for advanced glycosylation end product (RAGE)-dependent pathway. A novel PPAR-γ agonist, rosiglitazone, exhibits anti-inflammatory effect and reduces RAGE expression. The aim of this study was to determine whether rosiglitazone could prevent left ventricle (LV) diastolic dysfunction and attenuate myocardial fibrosis in type 2 diabetic rat. Methods : OLETF rats, a model of type 2 diabetes were divided into the untreated and rosiglitazone-treated (20mg/kg/d) groups. The rats were treated with rosiglitazone for 20 weeks. LETO rats were used as a nondiabetic control. At the age of 20 and 40 weeks, all rats underwent Doppler echocardiography. At the age of 40 weeks, the hearts were examined by histopathological and immunohistochemical analyses. Results : At the age of 40 weeks, the OLETF rats treated with rosiglitazone improved the parameters of LV diastolic function such as the E/A ratio (Treated vs. Untreated: 1.7 ± 0.1 vs. 1.5 ± 0.1, p<0.05), deceleration time (DT) (50 ± 3 vs. 59 ± 9 msec, p<0.05) and isovolumic relaxation time (IVRT) (29 ± 3 vs. 35 ± 3 msec, p<0.05) compared to the untreated OLETF rats. The LV collagen volume fraction (CVF) of rosiglitazone-treated OLETF rats was decreased than that of untreated OLETF rats (3.2 ± 1.3 vs. 5.7 ± 2.0% p<0.001), while it was not significant different from that of LETO rats. Rosiglitazone-treated OLETF rats had a significant decrease the percentage of staining of LV CTGF (7.4 ± 2.5 vs. 15.4 ± 4.7%, p<0.001) and RAGE (1.1 ± 0.4 vs. 2.0 ± 0.8%, p<0.001) compared with untreated OLETF rats. Conclusion : This concluded that rosiglitazone, insulin sensitizer, could prevent LV diastolic dysfunction and attenuate myocardial fibrosis in type 2 diabetic rat by inhibition of RAGE and CTGF expression. PPAR-γ agonist provides a potential therapeutic approach for diabetic heart disease.
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