目的 探讨选择性β_1受体阻滞剂比索洛尔联合还原型谷胱甘肽改善应激性心肌病心肌重构程度的作用。方法 构建雄性C57BL/6J小鼠应激性心肌病模型(n=60),按随机数字表法分为5组:(1)生理盐水组(Saline,0.5 ml腹腔注射,1次/d;n=9);(2)异丙肾上腺素组(ISO,50 mg/kg腹腔注射,1次/d;n=11);(3)ISO+比索洛尔组(Biso,10 mg/kg灌胃,1次/d;n=12);(4)ISO+还原型谷胱甘肽组(GSH,250 mg/kg灌胃,1次/d;n=12);(5)ISO+Biso+GSH组(n=16)。3周后分别从心脏超声、血流动力学、组织形态病理学及分子水平对各组心肌重构改善程度进行综合评价。结果(1)ISO+Biso+GSH组小鼠体重波动幅度较其他各组小,差异有统计学意义(F=2.48,P〈0.05);(2)ISO+Biso+GSH组小鼠心功能指标包括舒张末期左心室内径、收缩末期左心室内径、舒张末期左心室后壁厚度、短轴缩短率、射血分数、收缩期末压力、舒张期末压力、左心室最大上升速率及左心室最大下降速率均明显优于其余组(F=10.49,9.53,15.60,32.56,36.56,44.21,15.03,42.01和33.40,均为P〈0.001);(3)ISO+Biso+GSH组心重指数HW/BW、LW/BW及HW/TL与其他各组比较,差异有统计学意义(F=16.51,36.57和15.50,均为P〈0.001)。ISO+GSH组心重指数虽好于ISO+Biso组.但差异无统计学意义。反映心肌细胞肥厚及纤维化程度的HE、PSR及WGA染色定性分析以及心肌细胞横切面积、心肌间质胶原容积定量分析进一步证实,ISO+Biso+GSH组改善心肌重构的程度优于其他各组,差异有统计学意义(0.47%±0.05%比0.17%±0.01%,1.64%±0.01%,0.67%±0.08%和0.65%±0.04%,均为P〈0.05);(4)心肌肥厚标志物心房钠尿肽、脑利钠肽、β肌球蛋白重链以及心肌纤维化程度标志物结缔组织生长因子、转录生长因子β、胶原酶1α在ISO+Biso+GSH组明显下调。炎症反应标志物CRP3和TNF-α也同样下调,但SOD1和SOD2明
Objective To investigate the therapeutic effect of combined utilization of bisoprolol and glutathione (GSH) for attenuating ventricular remodeling of Takotsubo cardiomyopathy (TTC) in mice. Methods C57BL/6J male mice with TTC (n = 60) were randomly divided into five groups as: (1) saline control group ( n = 9), 0.5 ml saline intraperitoneal injection ( i. p) once a day ; (2) isoprenaline (ISO) control group ( n = 11 ) , 50 mg/kg ISO i. p once a day; ( 3 ) ISO + bisoprolol group ( Biso group, n = 12), 10 mg/kg bisoprolol intragastric administration( i. g) once a day; (4) ISO + GSH group ( GSH group, n = 12), 250 mg/kg GSH i. g once a day; (5) ISO + Biso + GSH group (Biso + GSH group, n = 16). Echocardiographic, haemodynamic, morphopatholoical and molecular data were analyzed for each group 3 weeks after given different treatment. Results ( 1 ) ISO + Biso + GSH group had a more stable body weight than other groups with a significant difference ( F = 2. 48, P 〈 0. 05). (2) Left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), interventricular septum (IVSD) and left ventricular posterior wall (LVPWD) , fractional shortening( FS), ejection fraction (EF) , end-systolic pressure( EDS), end-diastolic pressure( EDD), dp/dt max, and dp/dt rain in ISO + Biso + GSH group were superior to other groups respectively ( F = 10. 49, P 〈 0. 001 ; F = 9. 53, P 〈 0. 001 ; F = 15, 60, P 〈 0.001; F=32.56, P〈0.001; F=36.56, P〈0.001; F=44.21, P〈0.001; F= 15.03, P〈0.001; F --42.01, P〈0.001; F=33.40, P〈0.001). (3) Heart weight (HW)/bodyweight (BW) (mg/g), HW/tibial length (TL) (mg/mm) and lung weight (LW)/BW (mg/g) ratios in ISO + Biso + GSH group were better than other groups with the significant difference ( F = 16. 51, P 〈 0. 001 ; F = 36. 57, P 〈 0. 001 ; F = 15.50, P 〈 0. 001 ), wherease no statis