摘要
目的评价β1肾上腺素受体(AR)阻滞剂美托洛尔联合β2AR激动剂非诺特罗对扩张型心肌病大鼠Fas、FasL表达的影响。方法将异丙基肾上腺素诱导的心力衰竭大鼠32只随机分为美托洛尔组(11只),联合治疗组(11只),安慰剂组(10只)。治疗8周后有创血流动力学评价心功能,TUNEL法检测心肌细胞凋亡指数,Westernblot测定Fas及FasL表达。另外随机选取9只雄性Wistar大鼠作为对照组。结果美托洛尔组较安慰剂组左心室收缩末压(PES)、左心室压力最大上升速率(dp/dtmax)明显增高(P<0.05),左心室舒张末压(PED)、凋亡指数明显降低(P<0.01)。美托洛尔组较联合治疗组PES、dp/dtmax、左心室压力最大下降速率(dp/dtmin)进一步增高(P<0.05),PED、凋亡指数进一步降低(P<0.01)。安慰剂组Fas、FasL表达明显高于对照组(P<0.01),美托洛尔组及联合治疗组较安慰剂组Fas、FasL表达明显减低(P<0.01),联合治疗组较美托洛尔组进一步减低(P<0.05)。结论Fas、FasL信号系统的充分抑制很可能是β1AR阻滞剂联合β2AR激动剂使心肌细胞凋亡率进一步降低的重要机制之一。
Objective To evaluate the effect of β1 adrenergic receplor（AR） antagonist metoprolol combined with/β2AR agonist fenoterol on expression of Fas and FasI. in heart failure rats. Methods Nine male Wistar rats were randomly selected as control group. Isoproterenol-induced heart failure rats were randomly divided into metoprolol group （ n = 11）, combined treatment group （n= ll）,and placebo group （ n-10）. Cardiac funclion was evalualed by invasive hemodynamics, apoptosis index was measured by TUNEL,the expression of caspase 3 was detected by immuno histochemistry and the expression of Fas and FasL by Western blot after 8 weeks＇ treatment. Results Compared with placebo group,left ventricular end systolic pressure （PEs） and dp/dt were significantly increased,while left ventricular end diastolic pressure （PED） and apoptosis index were significantly decreased in metoprolol group. PEs ,dp/dt and dp/dtmin were further increased and PED,apoptosis index were further decreased in combined treatment group. The expression lew el of Fas and FasL in control group was significantly lower than that in plalebo group, that in metoprolol group and combined treatment group were significantly lower than that in placebo group. It was further decreased in combined treatment group. Conclusions β2AR agonist can strengthen the effect of β1AR antagonist, inhibit cardiomyocyte apoptosis and improve the cardiac function in heart failure rats. One of the mechanisms involves inhibition of the Fas/FasL system.
出处
《中华老年心脑血管病杂志》
CAS
北大核心
2008年第1期47-49,共3页
Chinese Journal of Geriatric Heart,Brain and Vessel Diseases
基金
黑龙江省教育厅科学技术研究项目(11511228)
黑龙江省卫生厅医学科研课题(2006-041)
