Ethoxysanguinarine Alleviates Angiotensin Ⅱ-induced Cardiac Fibrosis in Mice
Objective:To investigate the effect and mechanism of Ethoxysanguinarine(ETH)on cardiac fibrosis induced by An-giotensin Ⅱ(Ang Ⅱ)in mice.Methods:Cardiac fibrosis model of hypertensive mice induced by AngⅡwas established.The mice were randomly divided into blank group,model group,ETH-low,ETH-medium and ETH-high groups,positive drug group.ALL the mice except the blank group were injected with Ang Ⅱ at a rate of 500 ng/(kg·min)subcutaneously while the blank group was injected with the same volume of normal saline for four weeks.From the first day after surgery,the ETH-low,ETH-medium and ETH-high groups were given 0.1,1,and 10 mg/(kg·d)of ETH by gavage.Respectively,the blank group and the model group were given the same volume of normal saline,and the positive drug group was given 10 mg/(kg·d)of Valsartan.All groups were given drugs by con-tinuous gavage for 28 days.Masson staining and Sirius red staining were used to detect cardiac fibrosis and collagen deposition in mice.The expression of collagen I,collagen Ⅲ,proliferating cell nuclear antigen(PCNA),α-smooth muscle actin(α-SMA),fibro-nectin(FN)and TGF-β1/smad2/3 signaling pathway-related proteins TGF-β1,p-smad2,smad2,p-smad3 and smad3 were detected by Western blot.Results:Compared with the blank group,there was significant cardiac fibrosis and collagen deposition in mice car-diomyocytes in the model group,the protein expression of collagen-I,collagen Ⅲ,PCNA,α-SMA,FN,TGF-β1,p-smad2,smad2,p-smad3 and smad3 ratio in heart tissue were significantly up-regulated(P<0.05),which were significantly reverssed after ETH accom-panied with alleviation of cardiac fibrosis and collagen deposition in a dose-dependent manner(P<0.05).Conclusion:ETH can alleviate AngⅡ-induced cardiac fibrosis,the inhibition of TGF-β1/smad2/3 pathway may be one of the important mechanisms.
万方数据
维普
