The Study Of Collagen Remodeling In Rats With Furazolidone-induced Dilated Cardiomyopathy

Objective: To explore the relevant changes of collagen remodeling in SD rats with furazolidone induced dilated cardiomyopathy(DCM).Methods: Forty 2-week-old Sprague-Dawlay(SD) rats were used, 30 rats were treated with furazolidone(0.15mg/body weight(g) /day per gavage for 8 weeks, FZ group), 10 rats were treated by equal volume water daily per gavage for 8 weeks(Control group,CON).Results: After 8 weeks,survival rate was 100% in CON group(10/10) and 73.33% in FZ group(22/30). Body weight(161.81 ± 17.65) vs(228.60 ± 30.78)g was significantly decreased while heart weight/body weight ratio(4.71 ± 0.63) vs(3.98 ± 0.58) was significantly increased in FZ group(both P<0.05). Echocardiography revealed that both left ventricular ejection fraction(LVEF)(65.69 ± 8.45) vs(88.51 ± 3.91)% and left ventricular fraction shortening(LVFS)(32.09 ± 5.68) vs(53.51 ± 5.92)% were significantly reduced(P < 0.05), while left ventricular end-diastolic dimension(LVEDD)(0.59 ± 0.08) vs(0.50 ± 0.03)cm and left ventricular end-systolic dimension(LVESD)(0.47±0.09) vs(0.23±0.03)cm were significantly increased(P<0.05) in FZ rats compared to CON rats. HE staining showed that myocardial fibers were dyed uniform and neat. The nucleus structure of cardiomyocytes was clear, size was uniform in CON group. In FZ group, there were several changes, such as the myocyte hypertrophy,myocardial fibers arrangement disorder, part of the fiber breakage or even disappear and interstitial cell swelling. Masson staining demonstrated that there were visible neat rows of dyed red myocardial fibers and a small amount of collagen fibers around the blood vessels in CON group, while a large number of collagen fibers could be detected in disordered form in FZ group. In FZ group, collagen volume fraction(CVF)(16.39±2.06) vs(2.78±1.10)% was increased(P < 0.001) compared to CON group.Sirius red staining showed that the arrangement of myocardial fibers was neatly, a small amount of scarlet collagen fibers was found around myocardial interstitial or blood vessels in CON group.The content of collagen fiber increased, which was widely distributed in the myocardial interstitial in disordered arrangement in FZ group. The m RNA expression of myocardial ColⅠ(2.57±0.63) vs(1.01±0.17), ColⅢ(1.45±0.34) vs(1.01±0.16), N2B(2.56±0.57) vs(1.02 ± 0.24) and LOX(1.78 ± 0.79) vs(1.00 ± 0.06) were significantly upregulated, while m RNA expression of titin(0.50± 0.13) vs(1.01 ± 0.17) and N2BA(0.41±0.05) vs(1.03±0.32) were significantly downregulated in FZ group compared with CON group(all P<0.05). The degree of CCL(6.13±0.96) vs(5.18±0.12)( P<0.05) were significantly increased in FZ group than in CON group. Moreover, CCL was negatively correlated with LVEF and LVFS while positively correlated with LVEDD and LVESD in FZ group.Conclusion: FZ-induced DCM SD rat reflected the characteristics of the human DCM from general condition, heart echocardiography and histopathological changes. At the same time, the study of collagen composition and structural changes showed the changes of collagen remodeling and cardiac function in heart failure. Collagen cross-linking and cardiac function were negatively correlated in FZ- induced DCM SD rat, suggested that improving collagen remodeling is likely to become one of the effective means.in improvement of cardiac function in patients with DCM.