Xu Tongyi, Zhang Ben, Yang Fan, Cai Chengliang, Wang Guokun, Han Qingqi, Zou Liangjian
Department of Cardiothoracic Surgery, No. 401 Hospital of PLA, Qingdao, China; Department of Cardiothoracic Surgery, Changhai Hospital, Second Military Medical University, Shanghai, China.
Centre of Cardiovascular Surgery, Guangzhou General Hospital of Guangzhou Military Region, Guangzhou, China; Department of Cardiothoracic Surgery, Changhai Hospital, Second Military Medical University, Shanghai, China.
Biochem Biophys Res Commun. 2015 May 8;460(3):622-7. doi: 10.1016/j.bbrc.2015.03.079. Epub 2015 Mar 21.
Pathological cardiac hypertrophy, often accompanied by hypertension, aortic stenosis and valvular defects, is typically associated with myocyte remodeling and cardiac dysfunction. Exercise preconditioning (EP) has been proven to enhance the tolerance of the myocardium to cardiac ischemia-reperfusion injury. However, the effects of EP in pathological cardiac hypertrophy are rarely reported. 10-wk-old male Sprague-Dawley rats (n = 80) were randomly divided into four groups: sham, TAC, EP + sham and EP + TAC. Two EP groups were subjected to 4 weeks of treadmill training, and the EP + TAC and TAC groups were followed by TAC operations. The sham and EP + sham groups underwent the same operation without aortic constriction. Eight weeks after the surgery, we evaluated the effects of EP by echocardiography, morphology, and histology and observed the expressions of the associated proteins. Compared with the respective control groups, hypertrophy-related indicators were significantly increased in the TAC and EP + TAC groups (p < 0.05). However, between the TAC and EP + TAC groups, all of these changes were effectively inhibited by EP treatment (p < 0.05). Furthermore, EP treatment upregulated the expression of HSF1 and HSP70, increased the HSF1 levels in the nuclear fraction, inhibited the expression of the NF-κB p65 subunit, decreased the NF-κB p65 subunit levels in the nuclear fraction, and reduced the IL2 levels in the myocardia of rats. EP could effectively reduce the cardiac hypertrophic responses induced by TAC and may play a protective role by upregulating the expressions of HSF1 and HSP70, activating HSF1 and then inhibiting the expression of NF-κB p65 and nuclear translocation.
病理性心肌肥大通常伴有高血压、主动脉瓣狭窄和瓣膜缺损，典型地与心肌细胞重塑和心脏功能障碍相关。运动预适应（EP）已被证明可增强心肌对心脏缺血-再灌注损伤的耐受性。然而，EP在病理性心肌肥大中的作用鲜有报道。将80只10周龄雄性Sprague-Dawley大鼠随机分为四组：假手术组、主动脉缩窄（TAC）组、EP + 假手术组和EP + TAC组。两个EP组进行4周的跑步机训练，EP + TAC组和TAC组随后进行TAC手术。假手术组和EP + 假手术组进行相同手术但不进行主动脉缩窄。术后8周，我们通过超声心动图、形态学和组织学评估EP的作用，并观察相关蛋白的表达。与各自的对照组相比，TAC组和EP + TAC组中肥大相关指标显著升高（p < 0.05）。然而，在TAC组和EP + TAC组之间，EP治疗有效抑制了所有这些变化（p < 0.05）。此外，EP治疗上调了热休克因子1（HSF1）和热休克蛋白70（HSP70）的表达，增加了细胞核部分中HSF1的水平，抑制了核因子κB p65亚基（NF-κB p65）的表达，降低了细胞核部分中NF-κB p65亚基的水平，并降低了大鼠心肌中的白细胞介素2（IL2）水平。EP可有效减轻TAC诱导的心脏肥大反应，并可能通过上调HSF1和HSP70的表达、激活HSF1进而抑制NF-κB p65的表达和核转位发挥保护作用。
