橙皮素和秋水仙碱对心肌梗死大鼠心肌纤维化的影响

Effect of hesperidin and colchicine on myocardial fibrosis in rats with myocardial infarction

目的研究橙皮素与秋水仙碱配伍对心肌梗死大鼠心肌纤维化及Periostin蛋白、IgG4水平的影响。方法选择75只健康雄性大鼠,按照随机分组原则分为5组,分别为假手术组、模型对照组、橙皮素组、秋水仙碱组和橙皮素与秋水仙碱配伍组,每组15只。比较5组实验大鼠的心脏超声结果、纤维化程度及Periostin、免疫球蛋G4(IgG4)的水平、炎性指标的差异。结果5组实验大鼠的左心室射血分数(left ventricular ejection fraction,LVEF)(F=12.036,P=0.000)、左室短轴率(left ventricular fractional shortening,LVFS)(F=11.286,P=0.000)、左室舒张末期内径(left ventricular internal diameter at end-diastole,LVIDd)(F=25.663,P=0.000)和左室收缩末期内径(left ventricular internal diameter at end-systole,LVIDs)(F=29.654,P=0.000)之间的差异有统计学意义,经过两两比较,5组实验大鼠的LVEF、LVFS、LVIDd和LVIDs从高到低依次为假手术组、橙皮素与秋水仙碱配伍组、秋水仙碱组、橙皮素组和模型对照组,LVIDd和LVIDs从高到低依次为模型对照组、橙皮素组、秋水仙碱组、橙皮素与秋水仙碱配伍组、假手术组(P<0.05);假手术组大鼠心肌纤维排列较整齐,结构完整,细胞大小较正常,有较完整的细胞核,模型对照组大鼠心肌细胞的排列较紊乱,细胞的形态大小存在显著的差异,细胞质的染色呈现不均匀性,细胞内可见大量的炎性物质。而橙皮素与秋水仙碱配伍组大鼠心肌细胞的排列较橙皮素组和秋水仙碱组整齐,细胞大小的差异较橙皮素组、秋水仙碱组小;5组大鼠的Periostin(F=20.266,P=0.000)、IgG4(F=29.658,P=0.000)水平之间的差异有统计学意义,经过两两比较,5组大鼠的Periostin、IgG4水平从高到低依次为模型对照组、橙皮素组、秋水仙碱组、橙皮素与秋水仙碱配伍组、假手术组;5组实验大鼠的肿瘤坏死因子(tumor necrosis factor-α,TNF-α)(F=22.587,P=0.000)、白细胞介素-1β(interleukin-1β)(F=26.354,P=0.000)、白细胞介素-6(interleukin-6,IL-6)(F=33.544,P=0.000)之间的差异有统计学意义,经过两两比较,5组实验大鼠的TNF-α、IL-1β、IL-6从高到低依次为模型对照组、橙皮素组、秋水仙碱组、橙皮素与秋水仙碱配伍组、假手术组。结论用橙皮素与秋水仙碱配伍治疗心肌梗死大鼠,可通过对Periostin、IgG4水平的显著下调而改善其心肌纤维化程度,治疗效果显著。

Objective To study the effects of hesperidin combined with colchicine on myocardial fibrosis,Periostin protein and IgG4 levels in rats with myocardial infarction.Methods According to the principle of random grouping,75 healthy male rats were divided into 5 groups,namely sham operation group,model control group,hesperidin group,colchicine group,and hesperidin and colchicine combined group,15 in each group.The differences of the results of echocardiography,fibrosis degree,periodin,IgG4 and inflammatory index were compared among the 5 groups.Results There were significant differences in left ventricular ejection fraction(LVEF)(F=12.036,P=0.000),left ventricular fractional shortening(LVFS)(F=11.286,P=0.000),left ventricular internal diameter at end-diastole(LVIDd)(F=25.663,P=0.000)and left ventricular internal diameter at end-systole(LVIDs)(F=29.654,P=0.000)among the 5 groups.The LVIDd,LVIDs from high to low were model control group,hesperidin group,colchicine group,hesperidin and colchicine combined group and sham operation group,the difference was statistically significant(P<0.05).In the sham operation group,the myocardial fibers were arranged more orderly,the structure was complete,the cell size was normal,and there was a relatively complete nucleus.In the model control group,the myocardial cells were disordered,there were significant differences in the shape and size of the cells,the staining of the cytoplasm was uneven,and a large number of inflammatory substances could be observed in the cells.Compared with hesperidin group and colchicine group,the arrangement of cardiomyocytes in compatibility of hesperidin and colchicine was more orderly,and the difference of cell size was smaller.There were significant differences in the levels of Periostin(F=20.266,P=0.000)and IgG4(F=29.658,P=0.000)among the 5 groups.By pairwise comparison,the levels of Periostin and IgG4 in the 5 groups from high to low were model control group,hesperetin group,colchicine group,hesperidin and colchicine combined group and sham operation group.The levels of TNF-α(tumor necrosis factor-α)(F=22.587,P=0.000)and IL-1β(interleukin-1β)in 5 groups were significantly higher than those in control group.There were statistically significant differences in TNF-α,IL-6(interleukin-6)(F=26.354,P=0.000)and IL-6(F=33.544,P=0.000).The order of IL-6 from high to low was model control group,hesperidin group,colchicine group,hesperidin and colchicine combined group and sham operation group.Conclusion The combination of hesperidin and colchicine in the treatment of myocardial infarction rats can significantly reduce the levels of Periostin and IgG4,improve the degree of myocardial fibrosis,and the treatment effect is significant.