目的：探讨选择性β1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β1、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明显上调,同时促进心肌细胞凋亡的 Bax 下调而抑制心肌细胞凋亡的 Bcl-2却上调(均为 P ＜0.05)。结论比索洛尔联合还原型谷胱甘肽能更好地改善应激性心肌病心肌重构。
目的：探討選擇性β1受體阻滯劑比索洛爾聯閤還原型穀胱甘肽改善應激性心肌病心肌重構程度的作用。方法構建雄性 C57BL/6J 小鼠應激性心肌病模型(n =60),按隨機數字錶法分為5組：(1)生理鹽水組(Saline,0.5 ml 腹腔註射,1次/ d；n =9)；(2)異丙腎上腺素組(ISO,50 mg/ kg腹腔註射,1次/ d；n =11)；(3)ISO ＋比索洛爾組(Biso,10 mg/ kg 灌胃,1次/ d；n =12)；(4)ISO ＋還原型穀胱甘肽組(GSH,250 mg/ kg 灌胃,1次/ d；n =12)；(5)ISO ＋ Biso ＋ GSH 組(n =16)。3週後分彆從心髒超聲、血流動力學、組織形態病理學及分子水平對各組心肌重構改善程度進行綜閤評價。結果(1)ISO ＋ Biso ＋ GSH 組小鼠體重波動幅度較其他各組小,差異有統計學意義(F =2.48,P ＜0.05)；(2)ISO ＋ Biso ＋ GSH 組小鼠心功能指標包括舒張末期左心室內徑、收縮末期左心室內徑、舒張末期左心室後壁厚度、短軸縮短率、射血分數、收縮期末壓力、舒張期末壓力、左心室最大上升速率及左心室最大下降速率均明顯優于其餘組(F =10.49,9.53,15.60,32.56,36.56,44.21,15.03,42.01和33.40,均為 P ＜0.001)；(3)ISO ＋ Biso ＋ GSH 組心重指數 HW/ BW、LW/ BW 及 HW/ TL 與其他各組比較,差異有統計學意義(F =16.51,36.57和15.50,均為 P ＜0.001)。 ISO ＋ GSH 組心重指數雖好于 ISO ＋Biso 組,但差異無統計學意義。反映心肌細胞肥厚及纖維化程度的 HE、PSR 及 WGA 染色定性分析以及心肌細胞橫切麵積、心肌間質膠原容積定量分析進一步證實,ISO ＋ Biso ＋ GSH 組改善心肌重構的程度優于其他各組,差異有統計學意義(0.47％±0.05％比0.17％±0.01％,1.64％±0.01％,0.67％±0.08％和0.65％±0.04％,均為 P ＜0.05)；(4)心肌肥厚標誌物心房鈉尿肽、腦利鈉肽、β肌毬蛋白重鏈以及心肌纖維化程度標誌物結締組織生長因子、轉錄生長因子β1、膠原酶1α在 ISO ＋ Biso ＋ GSH組明顯下調。炎癥反應標誌物 CRP3和 TNF-α也同樣下調,但 SOD1和 SOD2明顯上調,同時促進心肌細胞凋亡的 Bax 下調而抑製心肌細胞凋亡的 Bcl-2卻上調(均為 P ＜0.05)。結論比索洛爾聯閤還原型穀胱甘肽能更好地改善應激性心肌病心肌重構。
목적：탐토선택성β1수체조체제비색락이연합환원형곡광감태개선응격성심기병심기중구정도적작용。방법구건웅성 C57BL/6J 소서응격성심기병모형(n =60),안수궤수자표법분위5조：(1)생리염수조(Saline,0.5 ml 복강주사,1차/ d；n =9)；(2)이병신상선소조(ISO,50 mg/ kg복강주사,1차/ d；n =11)；(3)ISO ＋비색락이조(Biso,10 mg/ kg 관위,1차/ d；n =12)；(4)ISO ＋환원형곡광감태조(GSH,250 mg/ kg 관위,1차/ d；n =12)；(5)ISO ＋ Biso ＋ GSH 조(n =16)。3주후분별종심장초성、혈류동역학、조직형태병이학급분자수평대각조심기중구개선정도진행종합평개。결과(1)ISO ＋ Biso ＋ GSH 조소서체중파동폭도교기타각조소,차이유통계학의의(F =2.48,P ＜0.05)；(2)ISO ＋ Biso ＋ GSH 조소서심공능지표포괄서장말기좌심실내경、수축말기좌심실내경、서장말기좌심실후벽후도、단축축단솔、사혈분수、수축기말압력、서장기말압력、좌심실최대상승속솔급좌심실최대하강속솔균명현우우기여조(F =10.49,9.53,15.60,32.56,36.56,44.21,15.03,42.01화33.40,균위 P ＜0.001)；(3)ISO ＋ Biso ＋ GSH 조심중지수 HW/ BW、LW/ BW 급 HW/ TL 여기타각조비교,차이유통계학의의(F =16.51,36.57화15.50,균위 P ＜0.001)。 ISO ＋ GSH 조심중지수수호우 ISO ＋Biso 조,단차이무통계학의의。반영심기세포비후급섬유화정도적 HE、PSR 급 WGA 염색정성분석이급심기세포횡절면적、심기간질효원용적정량분석진일보증실,ISO ＋ Biso ＋ GSH 조개선심기중구적정도우우기타각조,차이유통계학의의(0.47％±0.05％비0.17％±0.01％,1.64％±0.01％,0.67％±0.08％화0.65％±0.04％,균위 P ＜0.05)；(4)심기비후표지물심방납뇨태、뇌리납태、β기구단백중련이급심기섬유화정도표지물결체조직생장인자、전록생장인자β1、효원매1α재 ISO ＋ Biso ＋ GSH조명현하조。염증반응표지물 CRP3화 TNF-α야동양하조,단 SOD1화 SOD2명현상조,동시촉진심기세포조망적 Bax 하조이억제심기세포조망적 Bcl-2각상조(균위 P ＜0.05)。결론비색락이연합환원형곡광감태능경호지개선응격성심기병심기중구。
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 min 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) / body weight (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 statistical significance was found between ISO + GSH and ISO + Biso groups. In the follow-up experiment, the ISO + Biso + GSH group shows better myocardiac remodeling than other groups, that was confirmed by the stains of haematoxylin-eosin ( HE), picrosirius red (PSR), for membranes with FITC-conjugated WGA ( Wheat Germ Agglutinin, Invitrogen) and for nuclei with DAPI were used for reflecting the degree of cardiac hypertrophy and fibrosis, combined with the quantitative analysis of myocyte cross-sectional area and collagen volume fraction. The difference were statistical significant (0. 47% ± 0. 05% Vs. 0. 17% ± 0. 01% , 1. 64% ± 0. 004% , 0. 67% ± 0. 08% and 0. 65% ± 0. 04% , all P < 0. 05) . (4) The levels of atrial natriuretic peptide ( ANP), brain natriuretic peptide (BNP ) and beta myosin heavy chain ( β-MHC ), and connective tissue growth factor ( CTGF ), collagenase1a (Coll1α), and transforming growth factor-β1 (TGF-β1) were all down-regulated in ISO +Biso + GSH group. C-reactive protein 3 (CRP3) and tumor necrosis factor α ( TNF-α) were also down-regulated and superoxide dismutase 1(SOD1) and SOD2 were all up-regulated markedly. Bax was down-regulated and B-cell lymphoma-2 ( Bcl-2) up-regulated ( P < 0. 05) . Conclusions The ventricular remodeling of TTC could be improved markedly when combined using bisoprolol and GSH.
