阿利吉仑通过抑制炎症和凋亡反应改善小鼠心肌缺血再灌注损伤

Aliskiren protects against myocardial ischemia-reperfusion injury in mice by inhibiting inflammatory and apoptotic responses

目的通过建立小鼠心肌缺血再灌注损伤模型,探讨阿利吉仑对于改善心肌缺血再灌注损伤的药物效果及可能的作用机制。方法将C57小鼠分为假手术组、模型组、低剂量组、高剂量组。假手术组和模型组给予等量生理盐水灌胃,低剂量组和高剂量组分别给予25、50μg/g阿利吉仑灌胃。超声心动图检测各组小鼠心脏功能,ELISA检测各组肿瘤坏死因子-α(TNF-α)及白细胞介素-6(IL-6)水平。实时荧光定量PCR和蛋白免疫印迹实验检测凋亡通路相关因子的表达水平。结果本实验成功建立小鼠心肌缺血再灌注损伤模型。与假手术组比较,其他3组小鼠的每搏输出量、心输出量、收缩期末左心室前壁厚度、收缩期末左心室后壁厚度、舒张期末左心室后壁厚度均显著降低(P<0.05)。与模型组比较,低、高剂量组小鼠的左心室射血分数和左心室短轴缩短率明显升高(P<0.05),且随着阿利吉仑剂量的增加而呈浓度依赖性升高(P<0.05),但TNF-α和IL-6水平明显降低(P<0.05)。与假手术组比较,模型组的B淋巴细胞2蛋白(Bcl-2)的mRNA和蛋白表达量均显著降低(P<0.05),而Bcl-2相关X蛋白(Bax)的表达量明显增加(P<0.05)。阿利吉仑能增加Bcl-2的表达量(P<0.05),而使Bax的表达量明显下降(P<0.05)。结论阿利吉仑可以通过抑制炎症反应、调控凋亡相关通路,改善小鼠心肌缺血再灌注损伤,促进其心功能的恢复。

Aim Through establishing a mouse model of myocardial ischemia-reperfusion injury to explore the effect of Aliskiren on myocardial ischemia-reperfusion injury and its possible mechanism.Methods C57 mice were divided into sham group,modle group,low-dose Aliskiren group and high-dose Aliskiren group.Sham group and modle group were treated with the same amount of saline,low-dose Aliskiren group and high-dose Aliskiren group were treated with Aliskiren of 25μg/g and 50μg/g respectively.The effects of Aliskiren on the cardiac function of each group were examined by echocardiography,and the levels of tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)in each group were detected by ELISA.qRT-PCR and Western blot were used to detect the expression of B-cell lymphoma-2(Bcl-2)and Bcl-2 associated X protein(Bax).Results A mouse model of myocardial ischemia-reperfusion injury was successfully established.Compared with sham group,the stroke volume,cardiac output,left ventricular anterior wall end-systolic dimension,left ventricular posterior wall end-systolic dimension and diastolic dimension of the other three group mice were significantly decreased(P<0.05).Compared with modle group,the ejection fraction and fractional shortening of mice treated with low-dose or high-dose Aliskiren were significantly increased(P<0.05),and the increase is in a dose-dependent manner(P<0.05),while the levels of TNF-αand IL-6 were significantly decreased(P<0.05).Compared with sham group,both mRNA and protein expression of Bcl-2 in modle group were significantly decreased(P<0.05),while Bax expression was distinctly increased(P<0.05).Aliskiren could increase the expression of Bcl-2(P<0.05),while decrease the expression of Bax(P<0.05).Conclusion Aliskiren can improve myocardial ischemia-reperfusion injury and promote the recovery of cardiac function in mice by inhibiting inflammatory reaction and regulating apoptosis-related pathway.