We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Effect of IL-6-mediated STAT3 signaling pathway on myocardial apoptosis in mice with dilated cardiomyopathy.
- Authors
LI, Q.; YE, W.-X.; HUANG, Z.-J.; ZHANG, Q.; HE, Y.-F.
- Abstract
OBJECTIVE: To investigate the effect of interleukin-6 (IL-6) gene knockout on apoptosis of myocardial cells in mice with Coxsackievirus B3 (CVB3)-induced dilated cardiomyopathy (DCM) and its potential mechanism, so as to provide certain references for the clinical prevention and treatment of DCM. MATERIALS AND METHODS: A total of 40 male C57 mice were randomly divided into Sham group (n=20) and DCM group (n=20) using a random number table. Another 20 mice with IL-6 gene knockout were enrolled into DCM+IL-6 KO group (n=20). The DCM model was established via CVB3 repeated incremental infection. After 9 months, the heart weight/body weight (HW/BW) ratio of mice in each group was detected. The ejection fraction [EF (%)] and fraction shortening [FS (%)] of mice in each group were detected via two-dimensional ultrasonography. The cross-sectional area and pathological changes in myocardial cells in the heart in each group were determined using hematoxylin-eosin (HE) staining. The collagen content in myocardial tissues in each group was detected via Masson staining and picrosirius red (PSR) staining, and the expressions of Collagen I and Collagen III in myocardial tissues in each group were detected via immunohistochemistry. In addition, the myocardial apoptosis in myocardial tissues in each group was detected via terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining. Finally, the protein expression levels of B-cell lymphoma-2 (Bcl-2), Bcl-2 associated X protein (Bax), phosphorylated signal transducer and activator of transcription 3 (p-STAT3), and total STAT3 (t-STAT3) were detected via Western blotting. RESULTS: The expression of IL-6 messenger ribonucleic acids (mRNAs) in myocardial tissues in DCM group was significantly increased compared with that in Sham group (p<0.05). After IL-6 knockout, the HW/BW ratio of DCM mice significantly declined (p<0.05), and the cross-sectional area of myocardial cells was significantly reduced (p<0.05). According to the results of echocardiography, the cardiac function of mice in DCM+IL-6 KO group was significantly superior to that in DCM group, manifested as the significant increase in FS (%) and EF (%) (p<0.05). The results of Masson staining, PSR staining, and immunohistochemical staining showed that IL-6 knockout could reduce the collagen content and Collagen I and Collagen III expressions in myocardial tissues of DCM mice (p<0.05). Furthermore, it was found via TUNEL staining that the number of apoptotic myocardial cells in DCM+IL-6 KO group was markedly smaller than that in DCM group (p<0.05). At the same time, the Bax/Bcl-2 ratio in myocardial tissues in DCM+IL-6 KO group was lower (p<0.05). Finally, the results of Western blotting revealed that DCM+ IL-6 KO group had a lower phosphorylation level of STAT3 than DCM group (p<0.05). CONCLUSIONS: Inhibiting IL-6 gene may improve the DCM-induced myocardial remodeling through reducing myocardial apoptosis.
- Subjects
INTERLEUKIN-6; DILATED cardiomyopathy; COXSACKIEVIRUSES; IMMUNOHISTOCHEMISTRY; MESSENGER RNA
- Publication
European Review for Medical & Pharmacological Sciences, 2019, Vol 23, Issue 7, p3042
- ISSN
1128-3602
- Publication type
Article