Hydrogen sulfide-loaded microbubbles combined with ultrasound mediate thrombolysis and simultaneously mitigate ischemia-reperfusion injury in a rat hindlimb model
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Updated: Dec 7, 2025
A Thrombotic Stroke Model Based On Transient Cerebral Hypoxia-ischemia
Published on: August 18, 2015
Jiayuan Zhong1,2,3,4, Yili Sun1,3,4, Yuan Han1,3,4
1Department of Cardiology, State Key Laboratory of Organ Failure Research, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Background:
Thromboembolism and subsequent ischemia/reperfusion injury (IRI) remain major clinical challenges.
Objectives:
To investigate whether hydrogen sulfide (H2 S)-loaded microbubbles (hs-Mbs) combined with ultrasound (US) radiation (hs-Mbs+US) dissolve thrombi and simultaneously alleviate tissue IRI through local H2 S release.
Methods:
hs-Mbs were manufactured and US-triggered H2 S release was recorded. White and red thromboembolisms were established ex vivo and in rats left iliac artery. All subjects randomly received control, US, Mbs+US, or hs-Mbs+US treatment for 30 minutes.
Results:
H2 S was released from hs-Mbs+US both ex vivo and in vivo. Compared with control and US, hs-Mbs+US and Mbs+US showed comparable substantial decreases in thrombotic area, clot mass, and flow velocity increases for both ex vivo macrothrombi. In vivo, hs-Mbs+US and Mbs+US caused similarly increased recanalization rates, blood flow velocities, and hindlimb perfusion for both thrombi compared with the other treatments, with no obvious influence on hemodynamics, respiration, and macrophage vitality. More importantly, hs-Mbs+US substantially alleviated skeletal muscle IRI by reducing reactive oxygen species, cellular apoptosis, and proapoptotic Bax, caspase-3, and caspase-9 and increasing antiapoptotic Bcl-2 compared with other treatments. In vitro, hypoxia/reoxygenation-predisposed skeletal muscle cells and endothelial cells treated with normal saline solution exhibited similar trends, which were largely reversed by an H2 S scavenger or an inhibitor of Akt phosphorylation.
Conclusion:
hs-Mbs+US effectively dissolved both white and red macrothrombi and simultaneously alleviated skeletal muscle IRI through the US-triggered, organ-specific release of H2 S. This integrated therapeutic strategy holds promise for treating thromboembolic diseases and subsequent IRI.
Insights
Hydrogen sulfide (H2S)-loaded microbubbles with ultrasound effectively dissolve blood clots and reduce tissue damage. This combined therapy offers a promising new treatment for thromboembolic diseases and related ischemia/reperfusion injury.
Area of Science:
- Biomedical Engineering
- Cardiovascular Research
- Regenerative Medicine
Background:
- Thromboembolism and ischemia/reperfusion injury (IRI) pose significant clinical challenges.
- Current treatments for these conditions have limitations.
Purpose of the Study:
- To evaluate the efficacy of hydrogen sulfide (H2S)-loaded microbubbles combined with ultrasound (US) radiation (hs-Mbs+US) in dissolving thrombi.
- To determine if this combined therapy can simultaneously alleviate tissue IRI through localized H2S release.
Main Methods:
- hs-Mbs were manufactured, and US-triggered H2S release was quantified.
- Thromboembolisms were induced ex vivo and in rat iliac arteries.
- Subjects received control, US, Mbs+US, or hs-Mbs+US treatments.
Main Results:
- hs-Mbs+US demonstrated effective thrombus dissolution ex vivo and in vivo, increasing blood flow and perfusion.
- Skeletal muscle IRI was significantly alleviated by hs-Mbs+US, evidenced by reduced oxidative stress, apoptosis, and modulated Bcl-2/Bax expression.
- The therapeutic effects were linked to localized H2S release and Akt pathway modulation.
Conclusions:
- The hs-Mbs+US strategy effectively dissolves thrombi and mitigates skeletal muscle IRI.
- This integrated approach, utilizing organ-specific H2S release, shows potential for treating thromboembolic diseases and subsequent IRI.
