Abstract
Background Excessive activation of the nod-like receptor family pyrin domain containing 3(NLRP3) inflammasome plays a significant role in the progression of cardiac injury. In China, it has been well recognized that Chinese herbal medicine is markedly effective in treating cardiovascular diseases (CVDs). LuQi Formula (LQF) has been used clinically for more than 10 years and confirmed to be effective in improving cardiac function and inhibiting apoptosis. However, the specific mechanisms underlying its efficacy are mostly unknown. This study aimed to evaluate whether LQF could alleviate cardiac injury and apoptosis by regulating the NLRP3 inflammasome and the caspase-3/Bax pathway. Purpose In this study, we investigated the effects of LQF on cardiac remodeling in a mouse model of myocardial infarction (MI) in vivo. Methods Forty male C57BL/6 mice were randomly divided into four groups: the sham group, the model group, the LQF group, and the perindopril group, with a sample size (n) of 10 mice in each group. Except the sham group, the other groups received left anterior descending (LAD) coronary artery ligation to induce MI and then treated with LQF, perindopril, or saline. Six weeks after MI, echocardiography was used to evaluate cardiac structure and function. Myocardial tissue morphology was observed by haematoxylin and eosin (H&E) staining, and heart samples were stained with Masson's trichrome to analyse myocardial fibrosis. Myocardial hypertrophy was observed by fluorescent wheat germ agglutinin (WGA) staining. The expressions of NLRP3, ASC, Cle-caspase-1, IL-1β, TXNIP, Cle-caspase-3, Bcl-2, and Bax in heart tissues were assessed by western blot analysis. mRNA expressions of ANP and BNP in heart tissues were measured by RT-PCR. The expression of reactive oxygen species in myocardial tissue was detected by using a DCFH-DA probe. Results Echocardiographic analysis showed that compared with the model group, the left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) in the LQF and perindopril group were increased (P < 0.05), left ventricular internal diameter end diastole (LVIDd) and left ventricular internal diameter end-systole (LVIDs) were reduced (P < 0.05), and H&E and Masson's trichrome staining of cardiac tissues showed that LQF and perindopril could partially reverse ventricular remodeling and alleviate myocardial fibrosis (P < 0.05). WGA fluorescence results showed that compared with the model group, myocardial hypertrophy was significantly reduced in the LQF and perindopril group. We also found that LQF and perindopril reduce the oxidative stress response in the heart of MI mice. The protein expression of NLRP3, ASC, Cle-caspase-1, IL-1β, TXNIP, Cle-caspase-3, and Bax was downregulated in the LHF and perindopril treatment group, and Bcl-2 expression was upregulated. Conclusion LQF and perindopril significantly attenuated cardiac injury and apoptosis in the MI model. In addition, we found that LQF effectively inhibited the activation of the NLRP3/ASC/caspase-1/IL-1β cascade, decreased inflammatory infiltration, delayed ventricular remodeling, and downregulated caspase-3/Bax signaling, which can effectively reduce the apoptosis of cardiomyocytes. Perindopril showed the same mechanism.
Highlights
Chronic heart failure (CHF), characterized by high mortality and morbidity, is the final outcome of many cardiovascular diseases (CVDs) [1]
atrial natriuretic peptide (ANP) and brain type natriuretic peptide (BNP) are sensitive markers of myocardial dysfunction, which correlate positively with the severity of HF. us, ANP and BNP are important indicators to determine the progression and prognosis of HF [20]. e qRT-PCR analysis showed that Myocardial infarction (MI)-induced increases of Anp and Bnp mRNA expression were partly alleviated in LuQi Formula (LQF) and perindopril mice compared with model mice (Figures 1(g) and 1(h)). is revealed that LQF and perindopril have protective effects against cardiac function
To determine whether the effect of LQF and perindopril on improving cardiac function is related to the inflammasome, we studied the expression of NLRP3 inflammasome in the heart
Summary
Chronic heart failure (CHF), characterized by high mortality and morbidity, is the final outcome of many CVDs [1]. Myocardial infarction (MI) is one of the most important causes of heart failure (HF), and how to reduce cardiac dysfunction and HF risk after MI has always been the focus of CVD research [2]. An early inflammatory response might increase matrix degradation, causing the infarcted myocardial tissue to heal and form a scar. Erefore, moderate regulation of the inflammatory response after MI is very important for myocardial remodeling of the left ventricle to prevent HF [5]. Is study aimed to evaluate whether LQF could alleviate cardiac injury and apoptosis by regulating the NLRP3 inflammasome and the caspase-3/Bax pathway. We investigated the effects of LQF on cardiac remodeling in a mouse model of myocardial infarction (MI) in vivo. Myocardial hypertrophy was observed by fluorescent wheat germ agglutinin (WGA) staining. e expressions of NLRP3, ASC, Cle-caspase-1, IL-1β, TXNIP, Cle-caspase-3, Bcl-2, and Bax in heart tissues were assessed by western blot analysis. mRNA expressions of ANP and BNP in heart tissues were measured by RT-PCR
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