Preventive and therapeutic effects of alprostadil injection on myocardial fibrosis in diabetic rats and its mechanism

Objective To observe the preventive and therapeutic effects of alprostadil injection on myocardial fibrosis in diabetic rats and its underlying mechanism. Methods Forty SD rats were randomly divided into four groups: normal control group (NC group), diabetic model group (DM group), diabetes model + alprostadil group (DM + Alp group), diabetic model + valsartan group (DM + Val group). Rats in NC group were fed with normal diet, and rats in other three groups were fed with high fat and sugar diet for 8 weeks, and then they were received disposable intravenously injection of streptozotocin (STZ) accounting for 30 mg/kg to build diabetic model. Rats in different groups were given corresponding medication interventions. After 12 weeks, the cardiac functional status were tested, and cardiac index (H/B) and left ventricular mass index (LVMI) were calculated. Deposition situation of myocardial interstitial collagen fiber were observed with Masson staining, and myocardial collagen volume fraction (CVF) were estimated via Proplus 6.0 image analysis system. Content of hydroxyproline in myocardial tissue was tested by chloramine-T method, which represented the total collagen content, and Elisa kit was used to measure the concentration of Ang Ⅱ and TGF-β₁ of blood. Expression level of signaling pathways related protein TGF-β₁, Smad2, p-Smad2 and Smad7 were detected by Westernblotting. Results Compared with normal rats, cardiac functional status of diabetic rats were poor, H/B, LVMI, CVF and content of hydroxyproline in myocardial tissue increased significantly (P ＜ 0.01), concentration of Ang Ⅱ and TGF-β₁ in blood also increased significantly (P ＜ 0.01). All the indicators of rats who were given alprostadil or valsartan improved significantly, however, there was no statistically significant difference of various indicators between them (P ＞ 0.05). Conclusion Alprostadil injection can suppress myocardial fibrosis of diabetic rats to some extent by weakening excessive activation of TGF-β₁/Smads signal transduction pathway in myocardial tissue.