基于NLRP3信号轴探讨参葵通脉颗粒改善慢性心衰心肌重塑的作用

Effect and mechanism of Shenkui Tongmai Granule in the treatment of chronic heart failure model based on NLRP3 signal axis

目的:研究参葵通脉颗粒治疗慢性心衰大鼠心功能及心肌NLRP3信号轴的影响。方法:腹主动脉缩窄制备慢性心衰大鼠模型,随机分为模型组、参葵通脉颗粒0. 72g颗粒/kg、1. 44g颗粒/kg、2. 88g颗粒/kg组、阳性药洛汀新0. 9mg/kg组,另以10只不缩窄腹主动脉的大鼠为假手术组。各组均干预4周。小动物超声检测各组大鼠心功能; Western blot检测各组大鼠心肌核苷酸结合寡聚化结构域样受体蛋白3(NLRP3)、半胱天冬氨酸蛋白酶1 (Caspase-1)、白细胞介素1β(IL-1β)、白细胞介素18(IL-18)蛋白表达。实时荧光PCR检测超氧化物歧化酶(SOD)与血红素加氧酶-1(HO-1) mRNA的表达。结果:与假手术组比较,模型组大鼠LVEDD、LVESD显著升高,LVEF、FS显著降低;与模型组比较,参葵通脉颗粒0. 72g、1. 44g、2. 88g颗粒/kg组LVEDD、LVESD显著降低,LVEF、FS显著升高。与假手术组比较,模型组大鼠NLRP3、Caspase-1、IL-1β、IL-18蛋白表达水平显著增加,SOD、HO-1 mRNA水平显著降低;与模型组比较,参葵通脉颗粒0. 72g、1. 44g、2. 88g颗粒/kg组NLRP3、Caspase-1、IL-1β、IL-18蛋白表达水平显著降低,SOD、HO-1 mRNA水平显著增加。结论:参葵通脉颗粒可增强内源性抗氧化应激能力,降低慢性心衰心肌NLRP3信号轴的活化,这可能是其改善慢性心衰心肌重塑的作用机制之一。

Objective: To study the effect of Shenkui Tongmai Granule in the treatment of chronic heart failure and its possible mechanism. Methods: Abdominal aorta coarctation was used to establish chronic heart failure rat model. Rats were randomly divided into the model group,three doses of Shenkui Tongmai granule groups( 0. 72g/kg,1. 44g/kg,2. 88g/kg),0. 9mg/kg Lotensin positive control group and sham operation control group. Rats were administered with corresponding drugs,and those in the model group and the sham operation group were given equal volume of distilled water daily,for constantly 4 weeks. TUNEL staining was used to detect the programmed necrosis of myocardium in rats. The expressions of NLRP3,Caspase-1,IL-1β were detected by western blot. The expressions of superoxide dismutase( SOD) and heme oxygenase-1( HO-1) mRNA were detected by real-time fluorescence PCR. Results: Compared with the sham operation group,TUNEL staining positive cells and the expressions of NLRP3,Caspase-1,IL-1β in the model group were significantly increased. Compared with the model group,TUNEL staining positive cells and the expressions of NLRP3,Caspase-1,IL-1β in Shenkui Tongmai granule groups were significantly lower than those in the model group. Compared with sham operation group,the levels of SOD and HO-1 mRNA in the model group were significantly decreased. Compared with the model group,the levels of SOD and HO-1 mRNA in each group were significantly increased.Conclusion: Shenkui Tongmai Granule can increase the levels of SOD,HO-1 mRNA,inhibit the oxidant stress endogenously,and reduce the expression of NLRP3,which may be one of the mechanisms for the chronic heart failure treatment.