血管紧张素转化酶抑制剂改善糖尿病大鼠心肌间质重构的类效应研究

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（TGF-β）、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（10mg／kg，n=9）、卡托普君1组（50mg／kg，n=9）、贝那普开0组（10mg／kg，凡=9）、福辛普利组（5mg／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、TGF-β1、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，TGF-β1、TIMP-1蛋白及TIM-1 mRNA表达增高，MMP-1蛋白及MMP-1 mRNA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TGF-β1、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。

Class effect of ACEI in improving myocardial interstitial remodeling of diabetic rat

AIM: Through comparing 4 ACEIs' influence in cardiac index, expression levels of type Ⅰ, typeⅢ collagen, TGF-β_1 , MMP-1 and TIMP-1 of diabetic rats to investigate the class effect of the ACEIs in improving myocardial interstitial remodeling of diabetic rat. METHODS: 50 male SD rats were injected strep-tozotocin( STZ) to induce into diabetic mellitus(DM), then the rats were divided into model group ( n = 9), captopril treated group(50 mg/kg, n = 9), imidapril treated group(10 mg/kg, n=9), benazepril treated group(10 mg/kg, n = 9) and fosinopril treated group (5 mg/kg, n = 10). 10 male SD rats were choosed as normal control group. Immunohistochemistry was used to measure the expression levels of type Ⅰ, type Ⅲ collagen , transforming growth factor beta 1 (TGF-(3, ) protein, matrix metalloproteinases (MMP)-1 and tissue inhibitors of metalloproteinases (TIMP)-1 protein. The mRNA of MMP-1 and TIMP-1 mRNA were measured by RT-PCR. RESULTS: By the end of the experiment , the cardiac index and the ventricle index were significantly higher in the model group than those in the normal control group ( P < 0.05 ). The expression of type Ⅰ, type Ⅲ collagen, TGF-β_1 protein, TIMP-1 protein and mRNA were also significantly higher than in the normal control group while the expression of MMP-1 protein and mRNA were significantly lower. All the index was greatly improved in the treated groups compared with the model group. There were some difference exist in captopril among other three groups. CONCLUSION: Through increasing the expression of TGF-β_1 and TIMP-1, at the same time decreasing the expression of MMP-1, all the ACEIs could improve the myocardial interstitial remodeling, and the result was effected by the contribution to Ang Ⅱ.