关键词: 三磷酸肌醇受体, RhoA/Rho激酶, 信号转导, 心肌肥厚, RT-PCR, 免疫印迹法, 大鼠

Abstract: Objective Cardiac hypertrophy may be regulated primarily by hypertrophystimulating factors.However，little is known about the cardiac growthinhibitory factors that negatively regulate the formation of cardiac Hypertrophy. Recently，a RhoA/Rho kinase signaling pathway was found to be involved in cardiac hypertrophy.The inositol 1，4，5 trisphosphate receptor(IP-3R)is an intracellular Ca SUP>2+/SUP> release channel and specially inhibited by heparin.Heparin was shown to prevent the growth and proliferation of cardiovascular cells besides its wellcharacterized anticoagulant action. We postulated that activation of IP-3R mediated RhoA/Rho kinase pathway had a potential rote in regulation of cardiomyocyte hypertrophy and heparin may antagonize this signaling pathway. Methods Primary neonatal rat cardiomyocytes were cultured in fetal calf serum. Western blotting and RT-PCR were used to evaluate the protein and gene expression. Results IP-3(10SUP>-7/SUP>mol/L)caused a time-dependent increase in c-fos，c-myc， α-actin and βmajor histocompatibility complex (β-MHC) expression of cardiomyocytes(EM>P/EM>0.05).Stimulation of cardiomyocytes with lP3 revealed a timedependent increase in the expressions of RhoA and Rho kinase gene (EM>P/EM>0.05), and heparin could inhibit the effects above mentioned (EM>P/EM>0.05). Concl

Key words: Inositol 1, 5-trisphosphate receptor(IP-3R), RhoA/Rho kinase, Signaling transduction, Cardiac hypertrophy, RT-PCR, Western blotting, Rat