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SS-31 Protects Liver from Ischemia-Reperfusion Injury via Modulating Macrophage Polarization
Longcheng Shang1, Haozhen Ren1,2, Shuai Wang1,2
1Department of Hepatobiliary Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.
Abstract:
Ischemia-reperfusion injury (IRI) is a common complication in liver surgeries. It is a focus to discover effective treatments to reduce ischemia-reperfusion injury. Previous studies show that oxidative stress and inflammation response contribute to the liver damage during IRI. SS-31 is an innovated mitochondrial-targeted antioxidant peptide shown to scavenge reactive oxygen species and decrease oxidative stress, but the protective effects of SS-31 against hepatic IRI are not well understood. The aim of our study is to investigate whether SS-31 could protect the liver from damages induced by IRI and understand the protective mechanism. The results showed that SS-31 treatment can significantly attenuate liver injury during IRI, proved by HE staining, serum ALT/AST, and TUNEL staining which can assess the degree of liver damage. Meanwhile, we find that oxidative stress and inflammation were significantly suppressed after SS-31 administration. Furthermore, the mechanism revealed that SS-31 can directly decrease ROS production and regulate STAT1/STAT3 signaling in macrophages, thus inhibiting macrophage M1 polarization. The proinflammation cytokines are then significantly reduced, which suppress inflammation response in the liver. Taken together, our study discovered that SS-31 can regulate macrophage polarization through ROS scavenging and STAT1/STAT3 signaling to ameliorate liver injury; the protective effects against hepatic IRI suggest that SS-31 may be an appropriate treatment for liver IRI in the clinic.
Insights
SS-31 peptide effectively protects the liver from ischemia-reperfusion injury (IRI) by reducing oxidative stress and inflammation. This novel antioxidant peptide targets mitochondria to suppress harmful reactive oxygen species (ROS) and regulate macrophage polarization, offering a promising clinical treatment for liver IRI.
Area of Science:
- Hepatology
- Immunology
- Pharmacology
Background:
- Ischemia-reperfusion injury (IRI) is a significant clinical challenge in liver surgery, often leading to substantial organ damage.
- Oxidative stress and inflammatory responses are key contributors to liver injury during IRI.
- Mitochondrial-targeted antioxidants represent a promising therapeutic strategy, yet the role of SS-31 in hepatic IRI remains unclear.
Purpose of the Study:
- To investigate the protective effects of SS-31 against liver IRI.
- To elucidate the underlying protective mechanisms of SS-31 in hepatic IRI.
Main Methods:
- Assessment of liver injury using Hematoxylin and Eosin (HE) staining, serum ALT/AST levels, and TUNEL staining.
- Evaluation of oxidative stress markers and inflammatory responses post-SS-31 treatment.
- Analysis of SS-31's effect on reactive oxygen species (ROS) production and macrophage polarization (STAT1/STAT3 signaling).
Main Results:
- SS-31 treatment significantly attenuated liver injury, as evidenced by improved histological scores, reduced ALT/AST levels, and decreased apoptosis.
- SS-31 administration effectively suppressed oxidative stress and inflammatory markers.
- SS-31 reduced ROS production and inhibited M1 polarization of macrophages by regulating STAT1/STAT3 signaling, leading to decreased pro-inflammatory cytokine release.
Conclusions:
- SS-31 demonstrates significant protective effects against liver IRI.
- SS-31 ameliorates liver injury by scavenging ROS and modulating macrophage polarization via the STAT1/STAT3 pathway.
- SS-31 holds potential as a therapeutic agent for clinical treatment of liver IRI.
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