多沙唑嗪干预对α1肾上腺素能受体抗体介导的糖尿病大鼠心肌I型、Ⅲ型胶原表达的影响

The effect of doxazosin on the expression of myocardial type I and type HI collagen fibers in a1 -adrenergic receptors antibody mediated diabetic rats

目的探讨多沙唑嗪干预对抗α1肾上腺素能受体自身抗体（α1-AA）阳性糖尿病大鼠心肌I型、Ⅲ型胶原纤维表达的影响及其对心肌保护作用的可能机制。方法糖尿病造模成功后，采用α1-AA注射液100μg/100g于0、4、8、12、16周大鼠尾静脉注射5次，建立α1-AA介导的糖尿病大鼠模型。实验动物按随机数字表法随机分为糖尿病组（A组，n=10）、多沙唑嗪组（B组，n=10）、α1-AA组（C组，n=8）、a1-AA多沙唑嗪组（D组，n=8）。B组和D组给予多沙唑嗪0．36mg·kg-1·d。灌胃：A组和c组同时给予等体积生理盐水灌胃。16周后处死大鼠。采用免疫组织化学方法检测左心室心肌组织的I型、Ⅲ型胶原的表达；电镜下观察心脏超微结构的改变；苦味酸．酸性品红染色，观察各组大鼠心肌胶原纤维。结果各组间比较，大鼠血糖差异无统计学意义（P〉0．05）。C组的体重明显低于A组（P〈0．01）。给予多沙唑嗪干预后，B组、D组的体重分别高于A组、C组（P〈0．05或P〈0．01）；D组的糖尿病大鼠心肌中I型、Ⅲ型胶原表达明显低于C组（P〈0．05），B组心肌I型、Ⅲ型胶原表达亦低于A组（P〈0．05）；电镜下c组心肌病变最严重，线粒体减少，呈空泡变性，间质胶原增生，而D组心肌病变较c组明显减轻，B组心肌病变亦较A组明显减轻；c组心肌胶原纤维明显增多、排列紊乱，D组心肌胶原沉积较C组明显减轻。结论多沙唑嗪可通过抑制α1-AA阳性糖尿病大鼠心肌组织的I型、Ⅲ型胶原的表达，减轻糖尿病心肌间质纤维化，保护心肌。

Objective To observe the effects of doxazosin on the expression of type [ and type 1 collagen fiber in autoantibodies against a-adrenergic receptors （ cq -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） , oq-AA mediated group （group C, n = 8 ）,I-AA plus doxazosin treated group （group D, n = 8）. Group C and group D were injected cq-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 typeⅢ 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 II1 collagen fibers in myocardium in group D was lower than that in group C （ P〈0.05 ）. Expression of type I and type m 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 coUagen 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 HI collagen expressions in myocardium of -1 -AA mediated diabetic rats, resulting in alleviation of myocardial fibrosis and protection of myocardium in diabeticrats.