丹酚酸A对小鼠心脏骤停复苏后心功能的保护作用

The protective role of salvianolic acid A on cardiac function in mice after resuscitation from cardiac arrest

目的:探讨丹酚酸A(Sal A)对小鼠心肺复苏(CPR)后心功能的作用。方法:24只雌性C57BL/6小鼠随机分为3组,对照组小鼠不进行建模,实验组小鼠通过颈静脉注射氯化钾建立CPR模型,CPR后30 s给予注射Sal A(15 mg/kg)(Sal A组)和等体积生理盐水(Vehicle组),超声心动图分析小鼠左室射血分数和左室缩短分数,血流动力学仪器监测3 h内心脏血流动力学变化,并统计72 h内小鼠生存率。Western blot分析CPR后3 h心肌炎性因子白细胞介素(IL)-10和肿瘤坏死因子(TNF)-α水平。结果:与Vehicle组相比,Sal A组小鼠心脏功能指标包括左室射血分数[(61.19±2.02)%对(40.73±1.53)%]、左室短轴缩短率[(38.55±1.72)%对(26.09±1.82)%]、心输出量[(7.0±1.1)m L/min对(3.6±0.9)mL/min]、左室压力升高最大速率(dp/dtmax,左室收缩功能指标)[(5 407±298.7)mmHg/s对(4 100±479.7)mmHg/s]和左室压力降低最大速率(dp/dtmin,左室舒张功能指标)[(–5 796.0±249.6)mmHg/s对(–3 882±670.7)mmHg/s]均明显改善(P均<0.01),并且有更高的生存率(68.7%对33.3%,P<0.01)。与Vehicle组相比,Sal A组小鼠促炎因子TNF-α的蛋白表达水平明显降低(1.66±0.26对8.35±0.52,P<0.01),抗炎因子IL-10的蛋白表达水平明显升高(6.21±0.47对2.82±0.17,P<0.01)。结论:Sal A通过抑制CPR后炎性反应,改善小鼠心功能及预后。

Objective: To investigate the effect of salvianolic acid A(Sal A) on cardiac function in mice after cardiopulmonary resuscitation(CPR). Methods: Twenty-four female C57BL/6 mice were randomly divided into 3 group. The control group was not treated. Other mice were injected through jugular vein with potassium chloride for estabishing a CPR model. 30 s latter, they were randomly treated with Sal A(15 mg/kg)(Sal A group) or equal volume of normal saline(vehicle group). Left ventricular ejection fraction and fractional shortening were determined by echocardiography. Changes in cardiac hemodynamics and survival rate of mice within 72 h were recorded. Western blot analysis of myocardial inflammatory factors interleukin(IL)-10 and tumor necrosis factor(TNF)-α levels was performed 3 h after CPR. Results: Compared with the vehicle group, all indexes of cardiac function were significantly improved in the Sal A group, including left ventricular ejection fraction((61.19±2.02)% vs.(40.73±1.53)%,P<0.01), fractional shortening((38.55±1.72)% vs.(26.09±1.82)%, P<0.01), cardiac output((7.0±1.1) mL/min vs.(3.6±0.9)mL/min, P<0.01) and left ventricular systolic(dp/dtmax)((5 407±298.7) mmHg/s vs.(4 100±479.7) mmHg/s, P<0.01) and diastolic function(dp/dtmin)((-5 796±249.6) mmHg/s vs.(-3 882±670.7) mmHg/s, P<0.01), which was associated with a higher survival rate(68.7% vs. 33.3%, P<0.01). Western blotting showed that compared with the vehicle group, Sal A treatment significantly down-regulated factor TNF-α(1.66±0.26 vs.8.35±0.52, P<0.01), whereas up-regulated factor IL-10(6.21±0.47 vs. 2.82±0.17, P<0.01)expression. Conclusion: Sal A improves cardiac function and prognosis of mice by inhibiting the inflammatory response after CPR.