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目的:通过4种血管紧张素转化酶抑制剂(ACEI)类药物对糖尿病大鼠心脏指数、心肌胶原含量及转化生长因子(TGFβ-1)、基质金属蛋白酶及其抑制剂(MMP-1,TIMP-1)表达的影响,籍以了解不同ACEI药物减轻糖尿病大鼠心肌间质重构有无类效应。方法:50只SD大鼠用链脲佐菌素(STZ)注射制备糖尿病模型,成功后随机分为模型组(n=9)、咪达普利组(10 mg/kg,n=9)、卡托普利组(50 mg/kg,n=9)、贝那普利组(10 mg/kg,n=9)、福辛普利组(5 mg/kg,n=10),另取10只正常鼠作为正常对照组。免疫组化法测Ⅰ型胶原、Ⅲ型胶原、TGFβ-1、TIMP-1和MMP-1蛋白的表达,RT-PCR法测TIMP-1和MMP-1 mRNA的表达。结果:模型组心脏指数和左心室指数显著高于正常对照组(P<0.05),Ⅰ型胶原、Ⅲ型胶原的表达也增加,存在着心肌间质重构,TGFβ-1、TIMP-1蛋白及TIMP-1 mRNA表达增高,MMP-1蛋白及MMP-1mRNA表达减少。使用ACEI药物后,各项指标均有所改善,卡托普利某些指标与其余3组之间存在统计学差异(P<0.05)。结论:四种ACEI类药物都可通过减少TGFβ-1、TIMP-1的表达而增加MMP-1的表达而改善糖尿病心肌间质的重构,具有类效应,作用效果与对血管紧张素Ⅱ(AngⅡ)的不同影响有关。
AIM: To investigate the effects of four angiotensin converting enzyme inhibitors (ACEIs) on cardiac index, myocardial collagen content, transforming growth factor (TGFβ-1), matrix metalloproteinase (MMP) and its inhibitors -1) expression, in order to understand different ACEI drugs reduce myocardial remodeling in diabetic rats have no effect. Methods: Fifty Sprague-Dawley rats were randomly divided into model group (n = 9), Imidapril group (10 mg / kg, n = 9) and streptozotocin (STZ) Captopril group (50 mg / kg, n = 9), benazepril group (10 mg / kg, n = 9) and fosinopril group Ten normal mice served as normal control group. The expressions of type Ⅰ collagen, type Ⅲ collagen, TGFβ-1, TIMP-1 and MMP-1 were detected by immunohistochemistry. The expressions of TIMP-1 and MMP-1 mRNA were detected by RT- Results: The cardiac index and left ventricular index in the model group were significantly higher than those in the normal control group (P <0.05). The expressions of type Ⅰ collagen and type Ⅲ collagen also increased. There were myocardial interstitial remodeling, TGFβ-1 and TIMP-1 protein And TIMP-1 mRNA expression increased, MMP-1 protein and MMP-1 mRNA expression decreased. The use of ACEI drugs, the indicators have improved, some indicators of captopril and the remaining three groups there is a statistically significant difference (P <0.05). CONCLUSION: All four ACEIs can improve the myocardial remodeling of myocardium by decreasing the expression of TGFβ-1 and TIMP-1 and increasing the expression of MMP-1, which has the similar effects and effects on angiotensin Ⅱ Ang Ⅱ) of the different effects.