Effect of adjuvant therapy of Shenfu Injection on NOD-like receptor protein 3/cysteine-aspartic acid-specific protease 1 mediated pyroptosis signaling pathway and inflammatory factor levels in rats with acute myocardial infarction

Objective  To investigate the effect of adjuvant therapy of Shenfu Injection on NOD-like receptor protein 3 (NLRP3)/cysteine-aspartic acid-specific protease 1 (Caspase-1) mediated pyroptosis signaling pathway and inflammatory factor levels in rats with acute myocardial infarction (AMI).

Methods  A total of 40 rats were randomly divided into sham operation group, model group, betaloc group (0.9 mg/kg), and combination group (0.9 mg/kg betaloc combined with 6 mL/kg Shenfu Injection), with 10 rats in each group. The rats were treated by gavage continuously for 3 weeks. The levels of serum troponin I (cTnI), creatine kinase-MB (CK-MB), interleukin (IL)-6, IL-1β, and tumor necrosis factor-α (TNF-α) in rats were detected before modeling, after modeling, and at 3 weeks of treatment. Echocardiographic parameters such as left ventricular ejection fraction (LVEF), left ventricular end-systolic diameter(LVESD), left ventricular end-diastolic diameter (LVEDD), and myocardial infarction area were compared among groups after modeling and at 3 weeks of treatment. Real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) and Western blot were used to detect the mRNA and protein expression levels of NLRP3 and Caspase-1 in the myocardium.

Results  Compared with the sham operation group, the levels of cTnI, CK-MB, IL-6, IL-1β, TNF-α, myocardial infarction area, and the expressions of NLRP3 mRNA and Caspase-1 mRNA in the model group were significantly increased after modeling and at 3 weeks of treatment (P < 0.05); compared with the model group, the levels of cTnI, CK-MB, IL-6, IL-1β, TNF-α, myocardial infarction area, and the expressions of NLRP3 mRNA and Caspase-1 mRNA in the betaloc group and the combination group were significantly decreased at 3 weeks of treatment, and the above indicators in the combination group were significantly lower than those in the betaloc group (P < 0.05).

Conclusion  Adjuvant therapy of Shenfu Injection for AMI can further alleviate myocardial cell injury, shorten infarction size, and inhibit inflammatory response and pyroptosis activity.