Preventive Effects of Alprostadil on Myocardium against Doxorubicin Induced Myocardial Fibrosis in Rats
XIONG Meihong
ZHANG Zhi
Abstract：Objective:To investigate the protective effect of different doses of alprostadil on myocardiun against adriamycin-induced myocardial fibrosis in rats and its mechanism.Method:Sixty SD rats were randomly divided into 4 groups:normal control group(NC group),adriamycin group(ADM group),low-dose alprostadil group(LA group),and high-dose alprostadil group(HA group).The NC group did not received additional intervention measures.And the remaining groups were given an intraperitoneal injection of Adriamycin with a dose of 2.5 mg/kg once a week for 6 consecutive weeks.The drug was discontinued for 2 weeks.Alprostadil 1.25 μg/kg was intraperitoneally injected into the other region 5 days after the start of the experiment in LA group for 8 consecutive weeks.Alprostadil 5.0 μg/kg was intraperitoneally injected into the other region 5 days after the start of the experiment for 8 weeks in HA group.At the end of the experiment,echocardiography was used to evaluate the cardiac function,and the contents of malondialdehyde(MDA)and glutathione(GSH)were detected.Masson staining was used to observe the deposition of collagen fibers in myocardial interstitium under electron microscope.Western Blot was used to detect the expression of transforming growth factor-β1(TGF-β1)and phosphorylated Smad2 in myocardial tissue.Results:MDA in ACM group was significantly higher than that in NC group,GSH was significantly lower than that in NC group(P＜0.05).MDA was significantly lower and GSH was significantly higher in HA and LA groups than that in ACM group(P＜0.05).Compared with ACM group,the levels of left ventricular systolic pressure(LVSP),left ventricular end-diastolic pressure(LVEDP),cardiac index(H/B),and left ventricular mass index(LVMI)in ACM group significantly increased(P＜0.01).Compared with the ACM group,the levels of LVSP,LVEDP,H/B and LVMI in LA group and HA group significantly decreased(P＜0.01).Compared with the NC group,the levels of TGF-β1 and phosphorylated transcription factor Smad2 in the myocardial tissue of the ACM group significantly increased(P＜0.01);Compared with ACM group,the protein expression levels of TGF-β1 and p-Smad2 in the myocardial tissue of the LA and HA groups significantly decreased(P＜0.01).Compared with NC group,the expression of Smad7 in the myocardial tissue of ACM group decreased,while it increased in the LA and HA groups(P＜0.01).Conclusion:Alprostadil can reverse adriamycin-induced myocardial fibrosis in rats by inhibiting the TGF-β1/p-Smad2-mediated signal transduction pathway in myocardial tissue.
Keywords：myocardial fibrosisAlprostadilAdriamycinexperimental study
Publication Date：2025-04-25
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：5( 1160-1164 )