To study the effect of fosinopril on the expression of thrombospondin-1 of cardiomyocytes in experimental diabetic rats.

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 typeⅠ, collagen type Ⅲ, transforming growth factor-β₁(TGF-β₁), angiotensinⅡ, tumor growth factor-β₁(TGF-β₁) and thrombospondin-1 protein expression were determined by ABC immunohistochemical staining respectively, and the expression of TSP-1 mRNA was determined via RT-PCR. Also we evaluated the expression of TSP-1 in microvascular walls in cardiac.

Compared with the control group, the expression of collagen typeⅠ(0.36±0.02 vs 0.17±0.02, P<0.05), collagen type Ⅲ(0.35±0.03 vs 0.15±0.02, P<0.05), TGF-β₁(0.39±0.04 vs 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 vs 2.25±0.21, P<0.05).

Compared with the control group, fosinopril inhibited the expression of Collagen typeⅠ, 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.

Diabetic; Thrombospondin-1; Fosinopril; Transforming growth factor-β₁