The Role And Its Possible Mechanism Of Polyamines Derived From Cardiac Mast Cell In Myocardial Remodeling Induced By Pressure Overload In Rats

Objective To investigate the role and its possible mechanisms of polyamines from cardiac mast cell in myocardial remodeling induced by pressure overload.Methods?1?To observe the changes of mast cell number and the contents of polyamines in cardiac tissue of rats with pressure overload.Healthy male Sprague-Dawley?SD??160±10g?rats were randomly divided into abdominal aortic constriction?AAC group?,Sham group and Cromolyn Sodium?a mast cell stabilizer,which was given by intraperitoneal injection after abdominal aortic constriction surgery?group?CS group?.The toluidine blue staining method was used to observe the number changes of mast cell in cardiac tissue of each group.The contents of polyamines in the myocardium of each group were analyzed by using HPLC.?2?To study the relationship between cardiac mast cell and myocardial remodeling.Healthy male SD?160±10g?rats were randomly divided into AAC group,Sham group and CS group.MASSON staining was used to observe the degree of myocardial fibrosis;The heart weight index was measured.?3?To observe the effects of exogenously administration of polyamines on myocardial remodeling.Polyamines?putrescine,spermine,spermidine,the dose was 10mg/kg/d,respectively?were intraperitoneally injected into normal rats.Toluidine blue staining was used to observe the number changes of mast cell in cardiac tissue of each group i.Polyamines contents were measured by using HPLC,and MASSON staining was performed to observe the degree of myocardial fibrosis.The heart weight index was measured.?4?To observe the relationship between mast cell and mitochondrial permeability transition pore?MPTP?.The myocardial mitochondria of AAC group,CS group and Sham group were isolated,and the opening of MPTP was induced by 200?mol calcium ion solution.?5?To observe the relationship between polyamines and MPTP opening.Healthy male SD rats aged 4 weeks and 8 weeks were randomly divided into Sham group,PUT,SPD,and SPM group,respectively.Effects of polyamines?PUT,SPD and SPM,the dose is 10?mol?on the opening of the mitochondrial permeability transition pore was determined by Ca²⁺–induced swelling of isolated cardiac mitochondria from above groups,which is measured as a reduction in A₅₂₀.Results?1?Compared with Sham group,the cardiac mast cell in AAC group were significantly aggregated and the contents of polyamines were significantly increased?P<0.05?.Compared with AAC group,the aggregation of mast cell in CS group was significantly reduced and the polyamine contents were significantly reduced?P<0.05?.?2?Compared with Sham group,the cardiac heart weight index and myocardial fibrosis in AAC group rats were significantly increased?P<0.05?.Compared with AAC group,the heart weight index and myocardial fibrosis in CS group were significantly decreased?P<0.05?.?3?Compared with Sham group,after intraperitoneal injection injection of polyamines,the number of mast cell in PUT,SPD,and SPM groups was increased at 4weeks and 8 weeks,and there was a significant increase in PUT group?P<0.05?.Compared with Sham group,the number of myocardial mast cell was increased in PUT,SPD,and SPM groups.The PUT group was the most significant?P<0.05?.Compared with Sham group,the spermine content was increased in the PUT and SPD groups at 4 weeks?P<0.05?,the spermidine content in the SPD group was increased at 4 weeks?P<0.05?,and the putrescine content in the PUT group was increased?P<0.05?;at 8 weeks,the spermine content both in SPD and SPM groups was significantly increased?P<0.05?,and the content of spermidine in SPM group was significantly increased?P<0.05?.Compared with Sham group,the heart weight index in PUT,SPD and SPM groups at 4 weeks and 8 weeks was significantly increased?P<0.05?.Compared with the Sham group,although there was a increase tendency of fibrosis indexes in PUT group,SPM group and the SPM group at the4th and the 8th week,however,there was no significant difference between them,and there was a significant increase in PUT group only at the 8th week?P<0.05?.?4?Compared with Sham group,the opening of myocardial MPTP in AAC group rats was significantly increased.Compared with AAC group,opening of myocardial MPTP was significantly inhibited in CS group at the 4th and the 8th week?P<0.05?.?5?Compared with Sham group,PUT,SPD and SPM could lead to great increase in myocardial MPTP opening in normal rats at 4 and 8 weeks?P<0.05?.Conclusion One of the important mechanisms of mast cell-mediated pressure overload myocardial remodeling is the release of polyamine,which then participate in the induction of myocardial remodeling through the regulation of mitochondrial MPTP.