白介素1受体拮抗剂对大鼠心肌细胞缺血再灌注损伤的保护作用及机制研究

The protective effects of interleukin-1 receptor antagonist on myocardial ischemia-reperfusion injury of rats

目的探讨白介素1受体拮抗剂对大鼠心肌细胞缺血再灌注(I/R)损伤的保护作用及机制。方法选择30只成年SD雄性大鼠,采用酶法分离大鼠单个心室肌细胞并进行培养,分为5组:二甲基亚砜(DMSO)组、心肌缺血再灌注(I/R)组、白介素1受体拮抗剂(IL-1ra)+I/R组、2-氨基乙基二苯硼酸酯(2-APB)+I/R组、2-APB+IL-1ra+I/R组。测定细胞的收缩/舒张功能(静息细胞长度,收缩幅度,最大收缩速率,最大复长速率,达峰时间,复长90%时间)及钙瞬变相关指标[静息细胞钙离子浓度(F_0);细胞Ca^(2+)变化幅度(△FFI);细胞内钙离子衰退常数(Tau)]。结果与二甲基亚砜组比较,I/R组心肌细胞的收缩幅度与△FFI减小,差异均有统计学意义(均P<0.01)。与I/R组比较,2-APB+I/R组和IL-1ra+I/R组的心肌细胞收缩幅度与△FFI明显增大。结论 IL-1ra可以下调1,4,5-三磷酸肌醇受体(IP3R)蛋白的表达,减轻I/R后心肌细胞钙超载。

Objective To investigate the protective effects of interleukin-1receptor antagonist(IL-1ra)on myocardial ischemia-reperfusion injury(I/R)and its mechanisms.Methods Ventricular cardiomyocytes were isolated via enzymatic hydrolysis from30adult male Sprague Dawley(SD)rats and randomly divided into dimethyl sulfoxide(DMSO)group,I/R group,interleukin-1receptor(IL-1ra)+I/R group,2-aminoethoxydiphenyl borate(2-APB)+I/R and2-APB+IL-1ra+I/R group.Systolic and diastolic function(including the resting cell length,the peak shortening,the maximal velocity of shortening and relengthening,the time to peak shortening,the time to90%relengthening)and calcium transient indexes[including resting intracellular Ca2+levels(F0),intracellular Ca2+amplitude(△FFI),the decay constant of Ca2+transient(Tau)]of single ventricular cardiomyocyte were measured.Results The peak shortening(%cell length)and△FFI of cardiomyocytes were significantly lower in I/R group than in DMSO group and significantly higher in IL-1ra+I/R group and2-APB+I/R group than in I/R group(all P<0.01).Conclusion IL-1ra may downregulate the protein levels of inositol1,4,5-trisphosphate receptors(IP3R)and attenuate calciumoverload of cardiomyocytes in I/R.