通冠胶囊对气虚血瘀致心衰的保护作用实验研究

Experimental Study on the Protective Effect of Tongguan Capsules on Heart Failure Caused by Qi Deficiency and Blood Stasis

目的基于ERK1/2/GATA4信号通路阐明通冠胶囊治疗气虚血瘀致心衰的相关机制。方法以18个月龄老年小鼠皮下注射异丙肾上腺素(ISO)的方法构建气虚血瘀致心衰模型,通过心脏超声和心肺称重明确心衰情况,免疫印迹检测ERK1/2/GATA4蛋白表达,从而明确通冠胶囊对气虚血瘀致心衰的作用机制。结果小鼠心脏超声结果表明,模型组与空白对照组、美托洛尔组以及通冠胶囊组比较,左室舒张末前壁厚度(LVAWd)、左室收缩末前壁厚度(LVAWs)、左室舒张末后壁厚度(LVPWd)、左室收缩末后壁厚度(LVPWs)、射血分数(EF)、左室短轴缩短率(FS)均有明显减小(P<0.01),LVIDs有明显增大(P<0.01),小鼠心肺称重结果表明,模型组与空白对照组、美托洛尔组以及通冠胶囊组比较,心/胫以及肺/胫均增大(P<0.05)。蛋白印迹实验结果表明,模型组与空白对照组、美托洛尔组以及通冠胶囊组比较,P-ERK以及GATA4表达量均增加(P<0.05)。结论气虚血瘀过度激活ERK1/2/GATA4信号通路,导致心衰的发生,通冠胶囊能够通过抑制ERK1/2/GATA4信号通路,达到防治心衰的效果。

Objective:To elucidate the related mechanism of Tongguan Capsules in treating heart failure caused by qi deficiency and blood stasis based on ERK1/2/GATA4 signaling pathway.Methods:The HF model caused by qi deficiency and blood stasis was established by subcutaneous injection of isoproterenol(ISO)in 18-month-old mice.Heart failure was determined by echocardiography and cardiopulmonary weighing,and the expression of ERK1/2/GATA4 protein was detected by Western blotting,so as to clarify the mechanism of Tongguan Capsules on heart failure caused by qi deficiency and blood stasis.Results:The results of mouse cardiac ultrasound showed that compared with the blank control group,OMI group and Tongguan Capsules group,the LVAWd,LVAWs,LVPWd,LVPWs,EF,FS were significantly decreased in the model group(P<0.01),and the LVIDs were significantly increased(P<0.01).The results of cardiopulmonary weighing of mice showed that compared with the blank control group,OMI group and Tongguan Capsules group,the heart/shin and lung/shin were increased in the model group(P<0.05).The results of Western blotting experiments showed that the expression levels of P-ERK and GATA4 in the model group were increased compared with the blank control group,OMI group and Tongguan Capsule group(P<0.05).Conclusions:Qi deficiency and blood stasis excessively activate ERK1/2/GATA4 signaling pathway and lead to heart failure.Tongguan Capsules can prevent heart failure by inhibiting ERK1/2/GATA4signaling pathway.