心肌胶原代谢变化在糖尿病心肌病变发生中作用的实验研究

Experimental study on the effect of changes of myocardial col-lagen metabolism on the development of diabetic cardiomyopathy

目的:观察链脲佐菌素(streptozotocin,STZ)诱导糖尿病仓鼠心肌代谢变化,进一步理解糖尿病心肌病变的发病机理,为治疗提供新的思路。 方法:腹腔注射STZ建立糖尿病仓鼠动物模型,10周后观察心肌超微结构和病理改变,免疫组化法检测心肌Ⅰ,Ⅲ型胶原变化,明胶酶谱分析法检测心肌基质金属蛋白酶(matrix metallo proteinase,MMPs)活性变化, 同时应用生化、放免法检测血糖、糖化血清蛋白、血脂、胰岛素变化。结果:与正常对照组仓鼠相比,糖尿病组仓鼠血糖和糖化血清蛋白水平显著升高;血三酰甘油、总胆固醇和低密度脂蛋白也明显升高;病程10周的糖尿病仓鼠心肌Ⅰ,Ⅲ型胶原表达量(5.18±0.86和1.87±0.28)显著高于对照组(1. 92±0.27和1.11±0.12)(t=-8.132,-5.706.P<0.01),且以Ⅰ型胶原增高更为显著;糖尿病组仓鼠心肌MMP-2活性为对照组的256.17±31.32)％(t=-11.150,P<0.001)。 结论:腹腔注射STZ可诱导糖尿病心肌病变仓鼠动物模型;糖尿病心肌病变表现心肌胶原沉积和MMPs活性的增高,抑制MMPs的活性可能对糖尿病心肌病变具有治疗价值。

AIM: To observe the changes of myocardial collagen metabolism in strep-tozotocin(STZ) induced diabetic hamsters, and to enrich our understanding of the pathogenesis so as to provide a new idea for the therapy of diabetic cardiomyopathy. METHODS: Diabetic hamster model was established by intraperitoneal in-jection(IP) of STZ 40 mg/kg once a day for 3 days. After stabilization of diabetic state for 10 weeks. Immunohistochemistry was used to measure expression levels of type Ⅰ, and type Ⅲ collagen in diabetic and normal hamster hearts. Activities of matrix metalloproteinase (MMPs) were detected by using gelatin zymography. Levels of blood glucose, glycated serum protein (GSP), lipoproteins and insulin were determined by using biochemical or radioimmunoassay methods. RESULTS: Compared with the normal control group, the levels of blood glucose, GSP, triglycerides(TG), total cholesterol(CHO) and low density lipoprotein(LDL) in the diabetic group increased obviously. Levels of the expression of collagen Ⅰ and Ⅲ in the diabetic group(5. 18 ±0. 86, 1. 87 ± 0.28) were significantly higher than those in the control group (1. 92 ± 0.27, 1.11±0.12), (t= -8.132, P < 0.001; t= -5.706, P < 0. 01), and the expression of type Ⅰ collagen was much higher in diabetic group. The activity of MMP-2 was higher in diabetic group (256. 17 ± 31. 32)% than in the control group( t = - 11.150, P < 0. 001). CONCLUSION: Diabetic cardiomyopathy hamster models can be established by intraperitoneal injection of STZ. Diabetic cardiomyopathy is manifested by deposition of myocardial collagen and activation of MMPs, and the inhibition of MMPs activity may have some therapeutic values.