Dataset Information

Protective Mechanisms of Suxiao Jiuxin Pills () on Myocardial Ischemia-Reperfusion Injury in vivo and in vitro.

ABSTRACT:

Objective

To study the protective mechanism of Chinese medicine Suxiao Jiuxin Pills (, SXJ) on myocardial ischemia and reperfusion (I/R) injury.

Methods

Mouse myocardial I/R injury model was created by 30-min coronary artery occlusion followed by 24-h reperfusion, the mice were then divided into the sham group (n=7), the I/R group (n=13), the tirofiban group (TIR, positive drug treatment, n=9), and the SXJ group (n=11). Infarct size (IS), risk region (RR), and left ventricle (LV) were analyzed with double staining methods. In addition, H9C2 rat cardiomyocytes were cultured with Na₂S₂O₄ to simulate I/R in vitro. The phosphorylation of extracellular regulated protein kinases1/2 (ERK1/2), protein kinase B (AKT), glycogen synthase kinase-3β (GSK3β), and protein expression of GATA4 in nucleus were detected with Western blot assay.

Results

The ratio of IS/RR in SXJ and TIR groups were lower than that in I/R group (SXJ, 22.4% ±6.6%; TIR, 20.8%±3.3%; vs. I/R, 35.4%±3.7%, P<0.05, respectively). In vitro experiments showed that SXJ increased the Na₂S₂O₄-enhanced phosphorylation of AKT/GSK3β and nuclear expression of GATA4.

Conclusion

SXJ prevents myocardial I/R injury in mice by activating AKT/GSK3β and GATA4 signaling pathways.

SUBMITTER: Tan YF

PROVIDER: S-EPMC7283981 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Publications

Protective Mechanisms of Suxiao Jiuxin Pills () on Myocardial Ischemia-Reperfusion Injury in vivo and in vitro.

Tan Ya-Fang YF Yu Juan J Pan Wen-Jun WJ Qi Jian-Yong JY Zhang Min-Zhou MZ

Chinese journal of integrative medicine 20200610 8

<h4>Objective</h4>To study the protective mechanism of Chinese medicine Suxiao Jiuxin Pills (, SXJ) on myocardial ischemia and reperfusion (I/R) injury.<h4>Methods</h4>Mouse myocardial I/R injury model was created by 30-min coronary artery occlusion followed by 24-h reperfusion, the mice were then divided into the sham group (n=7), the I/R group (n=13), the tirofiban group (TIR, positive drug treatment, n=9), and the SXJ group (n=11). Infarct size (IS), risk region (RR), and left ventricle (LV) ...[more]

PMID: 32524394

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Project description:BackgroundMany studies have shown effective protection from myocardial ischemia-reperfusion injury (MIRI) in animal models, but few, if any, treatments have yielded a substantial reduction in clinical. Several studies showed significant therapeutic effects for the Chinese patent medicine Suxiao Jiuxin Pill (SJP) in MIRI, although the specific molecular mechanisms remain undefined. Recently, increasing evidence indicates an important role for m6A modification in autophagy regulation in MIRI, and SJP has not been investigated in this regard.MethodsIn vivo experiments were performed in a Wistar rat MIRI model. In vitro assays were conducted in hypoxia/reoxygenation (H/R)-treated H9c2 cells. H9c2 cells with ALKBH5 and GSK3β silencing were constructed by lentivirus transfection. TUNEL and Annexin V/PI assays were carried out for apoptosis detection. Then, m6A modification was detected with the EpiQuik m6A RNA methylation quantification kit, and GFP-RFP-LC3B was used to observe dynamic changes in autophagy. The autophagosome structure was assessed by Transmission electron microscopy. qPCR and immunoblot were performed for mRNA and protein analyses, receptively.ResultsSJP significantly mitigated MIRI in rats, reducing infarct size and myocardial apoptosis, and improving left ventricular function. In addition, SJP inhibited autophagy through the GSK3β/mTOR pathway in MIRI rats. In cultured H9c2 cells, SJP significantly inhibited H/R- related apoptosis and autophagic activity through the GSK3β/mTOR pathway. Additionally, SJP enhanced ALKBH5 expression in H/R cardiomyocytes, which is important in impaired m6A modification. Interestingly, ALKBH5 knockdown enhanced autophagy and apoptosis in H/R-induced cells, whereas SJP reversed these effects. Further experiments showed that autophagic activity and apoptosis enhanced by ALKBH5 deficiency are GSK3β/mTOR pathway dependent in H/R-treated H9c2 cells. After SJP administration the above effects were alleviated, suggesting SJP inhibited autophagy through the ALKBH5/GSK3β/mTOR pathway in H/R-induced cardiomyocytes. These effects of SJP were common to its two main constituents, including tetra-methylpyrazine (TMP) and borneol (BOR).ConclusionSJP improves MIRI in rats and alleviates autophagy and apoptosis in H9c2 cells through the ALKBH5/GSK3β/mTOR pathway, thanks to its two major constituents TMP and BOR.

Dataset Information

Protective Mechanisms of Suxiao Jiuxin Pills () on Myocardial Ischemia-Reperfusion Injury in vivo and in vitro.

Objective

Methods

Results

Conclusion

Publications

Protective Mechanisms of Suxiao Jiuxin Pills () on Myocardial Ischemia-Reperfusion Injury in vivo and in vitro.

Similar Datasets

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