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Updated: Feb 19, 2026
Improved Rodent Model of Myocardial Ischemia and Reperfusion Injury
Published on: March 7, 2022
High-concentration hydrogen protects mouse heart against ischemia/reperfusion injury through activation of
Ouyang Chen1,2, Zhiyong Cao3, He Li1,2
1Department of Navy Aviation Medicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai, 200433, People's Republic of China.
Insights
High-concentration hydrogen (HCH) protects the heart by activating the PI3K-Akt1 pathway. Inhibiting Akt1 blocks this protective effect, indicating its crucial role in HCH-induced cardioprotection.
Area of Science:
- Biomedical Science
- Cardiovascular Research
- Molecular Biology
Background:
- Ischemic heart disease remains a leading cause of mortality worldwide.
- Hydrogen has emerged as a potential therapeutic gas for various diseases.
- The specific molecular mechanisms underlying hydrogen's cardioprotective effects require further elucidation.
Purpose of the Study:
- To investigate the role of the PI3K-Akt1 signaling pathway in the cardioprotective effects of high-concentration hydrogen (HCH).
- To determine whether Akt1 activation is essential for HCH-mediated protection against cardiac injury.
Main Methods:
- In vivo studies using C57BL/6 mice subjected to ischemia-reperfusion (I/R) injury.
- Administration of HCH and specific inhibitors of PI3K (LY294002, wortmannin) and Akt1/Akt2 (A-674563, CCT128930).
- In vitro studies using isolated cardiomyocytes subjected to hypoxia-reoxygenation.
- Analyses included serum biochemistry, histology, Western blotting, and immunohistochemistry.
Main Results:
- HCH administration significantly reduced cardiac injury in I/R mice.
- HCH treatment led to increased phosphorylation of Akt1, but not Akt2.
- Inhibition of PI3K or Akt1 abolished the cardioprotective effects of HCH.
- In vitro studies confirmed Akt1's role in mediating hydrogen's protective effects on cardiomyocytes.
Conclusions:
- High-concentration hydrogen exerts significant cardioprotection against ischemia-reperfusion injury.
- The protective mechanism of HCH is dependent on the activation of the PI3K-Akt1 signaling pathway.
- Targeting the PI3K-Akt1 pathway may represent a novel therapeutic strategy for managing cardiac injury.
Abstract:
The study investigated the role of Akt1 through the cardioprotection of high-concentration hydrogen (HCH). C57BL/6 mice were randomly divided into the following groups: sham, I/R, I/R + HCH, I/R + HCH + LY294002 (PI3K inhibitor), I/R + HCH + wortmannin (PI3K inhibitor), I/R + LY294002, and I/R + wortmannin. After 45 min of ischemia, HCH (67% H2 and 33% O2) was administered to mice during a 90-min reperfusion. To investigate the role of Akt1 in the protective effects of HCH, mice were divided into the following groups: I/R + A-674563 (Akt1 selective inhibitor), I/R + HCH + A-674563, I/R + CCT128930 (Akt2 selective inhibitor), and I/R + HCH + CCT128930. After a 4-h reperfusion, serum biochemistry, histological, western blotting, and immunohistochemical analyses were performed to evaluate the role of the PI3K-Akt1 pathway in the protection of HCH. In vitro, 75% hydrogen was administered to cardiomyocytes during 4 h of reoxygenation after 3-h hypoxia. Several analyses were performed to evaluate the role of the Akt1 in the protective effects of hydrogen. HCH resulted in the phosphorylation of Akt1 but not Akt2, and Akt1 inhibition markedly abolished HCH-induced cardioprotection. Our findings reveal that HCH may exert cardioprotective effects through a PI3K-Akt1-dependent mechanism.
