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Tongxinluo Activates PI3K/AKT Signaling Pathway to Inhibit Endothelial Mesenchymal Transition and Attenuate Myocardial Fibrosis after Ischemia-Reperfusion in Mice

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Abstract

Objective

To investigate the potential role of Tongxinluo (TXL) in attenuating myocardial fibrosis after myocardial ischemia-reperfusion injury (MIRI) in mice.

Methods

A MIRI mouse model was established by left anterior descending coronary artery ligation for 45 min. According to a random number table, 66 mice were randomly divided into 6 groups (n=11 per group): the sham group, the model group, the LY-294002 group, the TXL group, the TXL+LY-294002 group and the benazepril (BNPL) group. The day after modeling, TXL and BNPL were administered by gavage. Intraperitoneal injection of LY-294002 was performed twice a week for 4 consecutive weeks. Echocardiography was used to measure cardiac function in mice. Masson staining was used to evaluate the degree of myocardial fibrosis in mice. Qualitative and quantitative analysis of endothelial mesenchymal transition (EndMT) after MIRI was performed by immunohistochemistry, immunofluorescence staining and flow cytometry, respectively. The protein expressions of platelet endothelial cell adhesion molecule-1 (CD31), α-smoth muscle actin (α-SMA), phosphatidylinositol-3-kinase (PI3K) and phospho protein kinase B (p-AKT) were assessed using Western blot.

Results

TXL improved cardiac function in MIRI mice, reduced the degree of myocardial fibrosis, increased the expression of CD31 and inhibited the expression of α-SMA, thus inhibited the occurrence of EndMT (P<0.05 or P<0.01). TXL significantly increased the protein expressions of PI3K and p-AKT (P<0.05 or P<0.01). There was no significant difference between TXL and BNPL group (P>0.05). In addition, the use of the PI3K/AKT pathway-specific inhibitor LY-294002 to block this pathway and combination with TXL intervention, eliminated the protective effect of TXL, further supporting the protective effect of TXL.

Conclusion

TXL activated the PI3K/AKT signaling pathway to inhibit EndMT and attenuated myocardial fibrosis after MIRI in mice.

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Authors and Affiliations

  1. Graduate School, Hebei University of Chinese Medicine, Shijiazhuang, 050090, China

    Ya-ru Wei, Xiao-qi Wang, Kun Ma, Jiao-jiao Gu & Zhen-hua Jia

  2. Shijiazhuang Yiling Pharmaceutical New Drug Evaluation Center, Shijiazhuang, 050035, China

    Yun-long Hou

  3. Hebei Institute of Integrated Traditional and Western Medicine, Shijiazhuang, 050035, China

    Yu-jie Yin, Lu Liu & Zhen-hua Jia

  4. National Key Laboratory for Innovation and Transformation of Luobing Theory, Shijiazhuang, 050035, China

    Yu-jie Yin, Lu Liu & Zhen-hua Jia

  5. Department of Cardiology, Hebei Yiling Hospital, Shijiazhuang, 050091, China

    Yu-jie Yin, Lu Liu & Zhen-hua Jia

  6. Graduate School, Hebei Medical University, Shijiazhuang, 050017, China

    Zhen Li, Yi Liu, Ning-xin Han, Zi-xuan Wang & Yuan-jie Hao

Authors
  1. Ya-ru Wei
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  2. Yun-long Hou
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Contributions

Jia ZH, Hou YL, and Yin YJ conceived and designed the corresponding project. Wei YR, Li Z, Han NX, and Wang ZX performed the experiments and analyzed the data. Wei YR participated in the design and prepared the paper. Hou YL, Yin YJ, Li Z, Han NX, and Liu L revised the manuscript. Wang ZX, Liu Y, Ma K, Wang XQ, Hao YJ and Gu JJ participated in the production of the MIRI model. All authors approved the final manuscript.

Corresponding author

Correspondence to Zhen-hua Jia.

Ethics declarations

The authors have no relevant conflicts of interest. The pharmaceutical company only provided drug support for this experiment and did not participate in the experimental process, data collection and statistics.

Additional information

Supported by the National Natural Science Foundation of China (No. 81973692), Traditional Chinese Medicine Innovation Project of Hebei Province (No. 223777120D) and High-Level Talent Funding Program of Hebei (No. E2020100001)

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Wei, Yr., Hou, Yl., Yin, Yj. et al. Tongxinluo Activates PI3K/AKT Signaling Pathway to Inhibit Endothelial Mesenchymal Transition and Attenuate Myocardial Fibrosis after Ischemia-Reperfusion in Mice. Chin. J. Integr. Med. (2024). https://doi.org/10.1007/s11655-024-3652-5

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  • DOI: https://doi.org/10.1007/s11655-024-3652-5

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