GW24-e3626 Effects of prescription of Jiashen on TGF-beta/Smads pathway after myocardial infarction in rats. (1st October 2013) - Nan, Xiaoli
Abstract : Objectives: This study was designed to study the effect of PJS on TGF-β/Smads pathway after MI in rats. Methods: Male Sprague-Dawley rats (9-10 weeks) were subjected to sham-MI or MI by ligating the left anterior descending coronary artery for 1 and 4 weeks. The rats were divided into five groups: sham, MI, PJS (3 g/kg/day), PJS (6 g/kg/day), and losartan (an AT1 antagonist, 10 mg/kg/day). The vehicle, PJS, or losartan was given by oral gavage once a day after MI. The expressions of TGF-β1, p-smad2, p-smad3 in the myocardium were assayed using Western-blot at 1 week or 4 weeks after MI. Results: At 1 week after MI, administration of PJS (3 or 6 g/kg/day) attenuated the increases in myocardial expression levels of TGF-β1, p-smad2 and p-smad3 compared with MI group (TGF-β1: 1.21 ± 0.06 or 1.06 ± 0.03 vs.1.37 ± 0.09, p < 0.0 5; p-smad 2: 1.88 ± 0.04 or 1.52 ± 0.11 vs. 2.09 ± 0.24, p < 0.05; p-smad3: 0.83 ± 0.01 or 0.5 ± 0.02 vs. 1.05 ± 0.120, p < 0.05). The greater effect was achieved at a dose of 6 g/kg/day. Losartan treatment also inhibited the increases in myocardial expression levels of TGF-β1, p-smad2 and p-smad3 compared with MI group (TGF-β1: 0.58 ± 0.03 vs. 1.37 ± 0.09, P < 0.05; p-smad2: 1.27 ± 0.02 vs. 2.09 ± 0.24, P < 0.05; p-smad3: 0.23 ± 0.01 vs.1.05 ± 0.12, P < 0.05). At 4 week after MI, administration of PJS (3 or 6 g/kg/day) attenuated the increases in myocardial expression levels of TGF-β1, p-smad2 and p-smad3 compared with MI group (TGF-β: 0.58 ± 0.03 or 0.69 ± 0.02 vs. 0.78 ± 0.01, p < 0.0 5; p-smad 2: 0.57 ± 0.04 or 0.77 ± 0.02 vs. 0.88 ± 0.05, p < 0.05; p-smad3: 0.50 ± 0.01 or 0.65 ± 0.02 vs. 0.78 ± 0.01, p < 0.05). The greater effect was achieved at a dose of 6 g/kg/day. Losartan treatment also inhibited the increases in myocardial expression levels of TGF-β1, p-smad2 and p-smad3 compared with MI group (TGF-β1: 0.42 ± 0.01vs. 0.78 ± 0.01, P < 0.05; p-smad2: 0.24 ± 0.57 vs. 0.88 ± 0.05, P < 0.05; p-smad3: 0.39 ± 1.87 vs. 0.78 ± 0.01, P < 0.05). Conclusions: Our studies showed PJS administered can significantly inhibite TGF-β/Smads pathway after MI in rats. The data indicate that PJS improves cardiac remodelling possibly via inhibiting TGF-β/Smads pathway. The results suggest that PJS may have a promising potential for the prevention and treatment of MI.