福辛普利对糖尿病大鼠心肌血栓素蛋白1mRNA和蛋白质表达的影响

目的研究福辛普利对链脲佐菌素诱导的糖尿病大鼠心肌组织血栓素蛋白1（TSP-1）表达的影响。方法30只13周龄健康雄性SD大鼠，腹腔注射1％链脲佐菌素（STZ），随机区组法分为糖尿病组（无药物干预，其中8周末组10只，12周末组10只）和福辛普利组（蒙诺片，10mg·kg^-1·d^-1，10只），另选8只健康雄性SD大鼠（等量蒸馏水腹腔注射）作为正常对照组。糖尿病组于8周末处理大鼠10只，余10只与福辛普利组及对照组于12周末时处理，免疫组化检测心肌间质Ⅰ、Ⅲ型胶原与转化生长因子-β1（TGF-β1）蛋白表达水平，心肌组织TSP-1蛋白表达和血管紧张素Ⅱ（AngⅡ）水平；RT．PCR检测心肌组织TSP-1mRNA表达水平。多个样本均数的比较采用单因素方差分析，两两比较采用q检验。结果与对照组比较，心肌细胞TSP-1阳性表达率增加（0．94±0．03VS0．15±0．02，P〈0．05）；AngⅡ水平增加（11．33±0．97VS6．11±0．48，P〈0．05）。心肌间微血管壁上TSP-1阳性表达光密度值与对照组比较无统计学差异。心肌细胞TSP-1表达阳性率低于12周末糖尿病组（0．30±0．02VS0．95±0．01，P〈0．05）。RT—PCR结果显示，心肌TSP-1mRNA水平在糖尿病组增加（2．01±0．41VS0．95±0．01，P〈0．05），而在福辛普利组减轻（1．02±0．01VS2．25±0．21，P〈0．05）。结论糖尿病性大鼠心肌间质纤维化严重可能与心肌组织水平高表达AngII及过表达TSP-1有关；福辛普利通过降低AngⅡ及TSP-1水平，下调TGF—β1活性，抑制心肌纤维化进程。

Fosinopril inhibits protein and mRNA expression of thrombospondin-1 in cardiocytes with experimental diabetic rats

Objective To study the effect of fosinopril on the expression of thrombospondin-1 of cardiomyocytes in experimental diabetic rats.Methods A total of 30 SD rats models with diabetes were established by intraperitoneal injection of STZ,and then divided into:diabetes group and fosinopril treatment group.Another 8 healthy rats were set as control group.Collagen type Ⅰ,collagen type Ⅲ,transforming growth factor-β1 (TGF-31),angiotensin Ⅱ,tumor growth factor-β1 (TGF-β1) and thrombospondin-1 protein expression were determined by ABC immunohistochemical staining respectively,and the expression of TSP-1mRNA was determined via RT-PCR.Also we evaluated the expression of TSP-1 in mierovascular walls in cardiac.Results Compared with the control group,the expression of collagen type Ⅰ (0.36 ± 0.02 vs0.17 ±0.02,P ＜0.05),collagen type Ⅲ(0.35 ±0.03 vs0.15 ±0.02,P＜0.05),TGF-β1 (0.39 ±0.04vs 0.17 ± 0.02,P ＜ 0.05 ),and levels of Ang Ⅱ ( 11.33 ± 0.97 vs 6.11 ± 0.48,P ＜ 0.05 ) were increased significantly in cardiac interstitial.In addition,TSP-1 was increased significantly in diabetic group when compared to the control group,and fosinopril suppressed these effects( TGF-β1 0.24 ± 0.07 vs 0.49 ±0.05,P ＜ 0.05 ).But there was no significant difference in expression of TSP-1 in microvascular walls among these groups.The numbers of microvascular walls were decreased in diabetic group,but fosinopril increased the number.TSP-1 mRNA were highly expressed in the diabetic group compare with the control group( 2.01 ±0.41 vs 0.95 ±0.01,P＜0.05),but fosinopril treatment decreased this high expression ( 1.02 ±0.01 vs2.25 ± 0.21,P ＜ 0.05).Conclusion Compared with the control group,fosinopril inhibited the expression of Collagen type Ⅰ,Collagen type Ⅲ,TGF-β1 and TSP-1.Fosinopril decreased the cardiac fibrosis through lowering the levels of Ang Ⅱ and TSP-1,which may suppressed the activity of transformation-β1 and increased the metabolism of cardiomyocytes.