Si-Miao-Yong-An decoction suppresses necroptosis by regulating the p53 pathway in myocardial ischemia/reperfusion injury

Figures

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  Fig. 1. TICs of SMYA by UHPLC-MS/MS. (A): Positive ion mode. (B): Negative ion mode.

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  Fig. 2. The cardiac structure and function parameters in mice of each group. (A) The scheme of the study design. (B) The survival curve of mice in this study. (C) Representative images of mice heart examined by echocardiography in each group. (D–G) Quantitative values of mouse heart structure and function, including left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS), left ventricular end-diastolic inner diameter (LVIDd) and left ventricular end-systolic inner diameter (LVIDs). Data represent mean ± SD (sham: n = 12; model: n = 9; SMYA-L: n = 10; SMYA-M: n = 10; SMYA-H: n = 11). *P < 0.05, **P < 0.01, ***P < 0.001, vs. sham group; ▲P < 0.05, ▲▲P < 0.01, ▲▲▲P < 0.001, vs. model group.

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  Fig. 3. SMYA reduced myocardial infarct size in mice with I/R injury. (A) Representative images of TTC staining for the myocardial infarct size in each group; (B) Quantitative graph of myocardial infarct size. Values were expressed as the mean ± SD (n = 3). *P < 0.05, **P < 0.01, ***P < 0.001, vs. sham group; ▲P < 0.05, ▲▲P < 0.01, ▲▲▲P < 0.001, vs. model group. The myocardial tissues were collected after echocardiography examination.

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  Fig. 4. SMYA alleviated myocardial histopathological injury and serum myocardial injury markers in mice with I/R injury. (A) H&E-stained myocardial tissue (scale = 50 μm); (B) Masson-stained myocardial tissue (scale = 50 μm); (C) Collagen fiber area percentage quantification (n = 3); (D) Serum CK-MB concentration (n = 6); (E) Serum LDH concentration (n = 6). Data: mean ± SD. *P < 0.05, **P < 0.01, ***P < 0.001 vs. sham; ▲P < 0.05, ▲▲P < 0.01, ▲▲▲P < 0.001, vs. model. The myocardial tissues were collected after echocardiography examination.

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  Fig. 5. The KEGG enrichment analysis of potential therapeutic targets18.

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  Fig. 6. SMYA inhibited the p53 signaling pathway in myocardial I/R injury mice. (A) Representative immunoblot band diagram immunoblots against p53, RIPK1, RIPK3 and MLKL in myocardial tissues; (B) Quantitative values of p53 relative protein expression; (C) Quantitative values of RIPK1 relative protein expression; (D) Quantitative values of RIPK3 relative protein expression; (E) Quantitative values of MLKL relative protein expression. Values were expressed as the mean ± SD, n = 3. *P < 0.05, **P < 0.01, ***P < 0.001, vs. sham group; ▲P < 0.05, ▲▲P < 0.01, ▲▲▲P < 0.001, vs. model group. The myocardial tissues were collected after echocardiography examination.

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  Fig. 7. Mechanism of SMYA in inhibiting necroptosis caused by myocardial I/R injury.