The effect of doxazosin on the expression of myocardial type I and type III collagen fibers in α1-adrenergic receptors antibody mediated diabetic rats

Objective To observe the effects of doxazosin on the expression of type Ⅰ and type Ⅲ collagen fiber in autoantibodies against α1-adrenergic receptors (α1-AA) positive diabetic rats,and to investigate the protective mechanism of doxazosin on cardiomyopathy of diabetic rats.Methods After establishment of diabetes model with streptozocin,diabetic rats were randomly divided into diabetic group (group A,n =10),doxazosin treated group (group B,n =10),α1-AA mediated group (group C,n =8),α1-AA plus doxazosin treated group (group D,n =8).Group C and group D were injected α1-AA (100 μg/100 g) by caudal vein at 0,4,8,12,and 16 weeks.Doxazosin (0.36 mg · kg-1 · d-1) was administered by lavage for 16 weeks in group B and group D,and other groups were given the same volume of saline every day.Expressions of type Ⅰ and type Ⅲ collagen fibers in myocardium of left ventricle were detected by immunohistochemical staining.Pathological changes in the myocardium were observed by both light and electron microscopes.Changes in collagen fiber in myocardium were detected by Van Gieson staining.Results Among various groups,there was no significant difference in blood glucose levels (P ＞ 0.05).After the intervention of doxazosin,body weight in group B and group D was greater than that of group A and group C (P＜0.05 or P＜0.01).Expression of type Ⅰ and type Ⅲ collagen fibers in myocardium in group D was lower than that in group C (P＜0.05).Expression of type Ⅰ and type Ⅲ collagen fibers in group B was lower than that in group A (P＜0.05) as well.Myocardial pathological changes in group C were most serious,showing reduced mitochondrial,vacuolar degeneration,and interstitial collagen hyperplasia.Cardiomyopathy in group D and group B was less marked as compared with that in group C and group A,respectively.Myocardial collagen fiber in group C was significantly increased and showed poor alignment.Compared with group C,myocardial collagen deposition in group D was obviously reduced.Conclusions Doxazosin may suppress type Ⅰ and type Ⅲ collagen expressions in myocardium of α1-AA mediated diabetic rats,resulting in alleviation of myocardial fibrosis and protection of myocardium in diabetic rats. Key words: Doxazosin;  Autoantibodies against α1-adrenergic receptors;  Diabetic rats;  Type Ⅰ and type Ⅲcollagen fiber