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. 2019 Oct 11:10:1286.
doi: 10.3389/fphys.2019.01286. eCollection 2019.

Aerobic Exercise Ameliorates Myocardial Inflammation, Fibrosis and Apoptosis in High-Fat-Diet Rats by Inhibiting P2X7 Purinergic Receptors

Xudong Chen  1   2 , Haiyan Li  3 , Kangwei Wang  1 , Xiaohe Liang  1 , Weiqi Wang  1 , Xiaokang Hu  1 , Zhouqing Huang  4 , Yonghua Wang  5
Affiliations

Aerobic Exercise Ameliorates Myocardial Inflammation, Fibrosis and Apoptosis in High-Fat-Diet Rats by Inhibiting P2X7 Purinergic Receptors

"VSports注册入口" Xudong Chen et al. Front Physiol. .

Abstract

Background: High-fat-diet (HFD) is associated with chronic low-grade inflammation. P2X7 purinergic receptors (P2X7R) are key regulators of inflammasome activation VSports手机版. The benefits of exercise are partly attributed to its anti-inflammatory effect, but whether it regulates P2X7R expression to improve remodeling in cardiac myocytes treated by HFD is not completely clarified. .

Methods: Three groups of Sprague-Dawley (SD) rats were studied: (1) control group (fed a normal chow diet), (2) HFD group, and (3) HFD+ exercise group. H9c2 myocytes were pretreated with or without A438079 (a P2X7R inhibitor) and then exposed to 200 μM palmitic acid (PA) for 24 h. The levels of mRNA and protein were measured by real-time PCR and Western blot, respectively. Masson staining and hematoxylin-eosin (HE) staining were used to identify remodeling of the heart. The concentration of IL-1β in serum or supernatants were measured by ELISA V体育安卓版. .

Results: In vivo, collagen deposition and the number of disordered cells significantly increased in the hearts of the HFD group compared to the control group. However, exercise markedly reversed these changes in the myocardium, and the same trends were observed in the expression of MMP9, collagen I and TGF-β V体育ios版. Notably, the expression of P2X7R, NLRP3, caspase-1 in the hearts, and serum IL-1β level were also greatly upregulated in the heart of the HFD diet rats, and all these changes were ameliorated in the HFD + EX group. As expected, exercise also reduced the number of TUNEL-positive cells, which was consistent with the caspase-3, Bax, and Bcl-2 results. Moreover, exercise reduced body weight and blood lipid concentrations in the HFD diet rats. In vitro, we observed that the hallmark of fibrosis, inflammation and apoptosis in H9c2 myocytes enhanced by PA, and the P2X7R inhibitor treatment significantly reduced the expression of the NLRP3, caspase-1, suppressed the secretion of IL-1β of H9c2 cells, inhibited collagen I, TGF-β, MMP9, Bax, caspase-3 levels and increased the expression of Bcl-2, compared with the PA group. In addition, a decrease of the number of TUNEL-positive cells used by A438079 further support that cardiomyocytes apoptosis could be inhibited. .

Conclusion: Aerobic exercise reversed the cardiac remodeling via the reduction of inflammation, fibrosis and apoptosis in HFD rats, at least in part through inhibiting P2X7R expression in cardiomyocytes VSports最新版本. .

Keywords: P2X7 purinergic receptors; aerobic exercise; apoptosis; fibrosis; high-fat-diet; inflammation. V体育平台登录.

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Figures

FIGURE 1
FIGURE 1
Changes in body weight and blood lipid levels. (A) Body weight was measured before and after 12 weeks of the treadmill exercise. (B) Blood lipid levels after 12 weeks of the treadmill exercise. TG, triglyceride; TC, total cholesterol; LDL, low-density lipoprotein; HDL, high-density lipoprotein. ∗p < 0.05 versus the CON group, #p < 0.05 versus the HFD group.
FIGURE 2
FIGURE 2
Regular aerobic exercise decreased myocardial inflammation in HFD rats. (A) Representative Western blot analysis of P2X7R. (B) The mRNA levels and the protein semiquantification are shown for P2X7R. (C) Representative Western blot analysis of NLRP3 and caspase-1. (D) The mRNA levels and the protein semiquantification are shown for NLRP3. (E) The mRNA levels and the protein semiquantification are shown for caspase-1. (F) Concentrations of IL-1β in the serum were detected by ELISA. ∗p < 0.05 versus the CON group, #p < 0.05 versus the HFD group.
FIGURE 3
FIGURE 3
Regular aerobic exercise decreased myocardial remodeling in HFD rats. (A) Representative images of Masson stained and HE stained rat left ventricles. (B) Representative Western blot analysis of MMP9. (C) The mRNA levels and the protein semiquantification are shown for MMP9. (D) Representative Western blot analysis of TGF-β. (E) The mRNA levels and the protein semiquantification are shown for TGF-β. (F) Representative Western blot analysis of collagen I. (G) The mRNA levels and the protein semiquantification are shown for collagen I. ∗p < 0.05 versus the CON group, #p < 0.05 versus the HFD group.
FIGURE 4
FIGURE 4
Regular aerobic exercise inhibited myocardial apoptosis in HFD rats. (A) Representative TUNEL stained images of rat left ventricles. (B) The percentage of TUNEL-positive cells are shown. (C) Representative Western blot analysis of caspase-3, Bcl-2, and Bax. (D) The mRNA levels and the protein semiquantification are shown for caspase-3. (E) The mRNA levels and the protein semiquantification are shown for Bcl-2. (F) The mRNA levels and the protein semiquantification are shown for Bax. ∗p < 0.05 versus the CON group, #p < 0.05 versus the HFD group.
FIGURE 5
FIGURE 5
The P2X7R inhibitor suppressed PA-induced inflammation, fibrosis and apoptosis in cardiomyocytes. (A) Cell viability was assessed by the CCK8 assay. H9c2 myocytes were incubated in a medium with A438079 at 0–80 μM for 12 h, and cells without A438079 treatment served as the control. (B) H9c2 myocytes were incubated in a medium with PA at 0–800 μM for 24 h, and cells without PA treatment served as the control. (C) Concentrations of IL-1β in cell culture supernatants were detected by ELISA. (D) Representative Western blot analysis of P2X7R, NLRP3 inflammasome, collagen I, MMP9, TGF-β, caspase-1, caspase-3, Bax, and Bcl-2. (E) The protein semiquantification is shown for P2X7R, NLRP3 and caspase-1. (F) The protein semiquantification is shown for collagen I, MMP9 and TGF-β. (G) The protein semiquantification is shown for caspase-3, Bax, and Bcl-2. (H) The percentages of TUNEL-positive cells are shown. (I) Representative images of TUNEL stained H9c2 myocytes. CON, H9c2 myocytes without any treatment; PA, H9c2 myocytes treated with 200 μM PA for 24 h; PA + A438079, H9c2 myocytes pretreated with A438079 for 12 h, and then treated with 200 μM PA for 24 h. ∗p < 0.05 versus the CON group, #p < 0.05 versus the HFD group.
FIGURE 6
FIGURE 6
Schematic model for the exercise-mediated amelioration of inflammation, fibrosis, and apoptosis.
See this image and copyright information in PMC

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