Di-san junyi daxue xuebao (Jul 2021)

Guanxin Salvia Miltiorrhiza Preparation protects rat cardiomyocytes against ischemia/reperfusion injury through miR-330-3p/ALDH2

  • YUAN Fang,
  • YANG Yanhua,
  • ZHAO Xinyang,
  • LI Lei

DOI
https://doi.org/10.16016/j.1000-5404.202101061
Journal volume & issue
Vol. 43, no. 13
pp. 1243 – 1252

Abstract

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Objective To explore the cardioprotective effectiveness of Guanxin Salvia miltiorrhiza (GXDS) Preparation (a prescribed Chinese herbal formula) and its relationship with inhibition of mast cell degranulation, and investigate the underlying mechanism. Methods Cardiomyocytes H9C2 (2-1) cocultured with mast RBL-2H3 cells cells were transfected with miR-330-3p mimics or ALDH2 Vector, or treated with GXDS or Compound 48/80, a mast cell degranulator. The expression of miR-330-3p and ALDH2 was detected by PCR and Western blotting, and cell proliferation and apoptosis were detected by MTT assay and flow cytometry. Mast cell degranulation and trypsin release were detected by ELISA, and the targeted binding of mast cell degranulation and trypsin release was detected by double luciferase reporter gene. Then, a rat model of myocardial ischemia/reperfusion injury was established by ligating the left anterior descending coronary artery for 30 min followed by reperfusion for 120 min. Then Compound 48/80 or GXDS was used to treat the rats with myocardial injury or sham operation. The myocardial injury was detected by immunohistochemistry in different treatment groups. Results Compound 48/80 inhibited the viability and promoted the apoptosis of H9C2 (2-1) and RBL-2H3 cells, and increased the releases of cTnI and trypsin (P < 0.05). GXDS treatment could promote the viability and inhibit the apoptosis of cardiomyocytes through miR-330-3p/ALDH2 (P < 0.05), and inhibit mast cell degranulation (P < 0.05). Compared with the sham operation rats, the hemodynamic abnormalities, arrhythmia, cardiac edema, infarct size, histopathological damages and levels of cTnI and miR-330-3p were significantly increased and the expression of ALDH2 was down-regulated in the rats of the model group (P < 0.05). GXDS pretreatment protected myocardium by inhibiting mast cell degranulation and trypsin release. Conclusion GXDS inhibits the degranulation of rat cardiac mast cells through miR-330-3p/ALDH2, and thus improves the myocardial ischemia/reperfusion injury.

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