Proanthocyanidin Alleviates Liver Ischemia/Reperfusion Injury by Suppressing Autophagy and Apoptosis via the PPARa/PGC1a Signaling Pathway

Background and Aims: Hepatic ischemia-reperfusion injury (IRI) is a common pathophysiological phenomenon in clinical practice, which usually occurs in liver transplantation, liver resection, severe trauma, and hemorrhagic shock. Proantho-cyanidin (PC), exerted from various plants with antioxidant, antitumor, and antiaging activity, were administrated in our study to investigate the underlying mechanism of its protec-tive function on IRI. Methods: Two doses of PC (50 mg/kg, 100 mg/kg) were given to BALB/c mice by intragastric ad-ministration for 7 days before partial (70%) warm IR surgery. Serum and liver tissues were collected 2, 8, and 24 h after reperfusion for relevant experiments. Results: The results of transaminase and hematoxylin and eosin staining indicated that PC pretreatment significantly alleviated IRI in mice. Se rum total superoxide dismutase increased and malondialde-hyde decreased in PC pretreatment groups. Enzyme-linked immunosorbent assays, western blotting, quantitative real-time polymerase chain reaction, and immunohistochemistry showed that inflammation, apoptosis, and autophagy in PC preprocessing groups were significantly inhibited and were dose-dependent. The protein, mRNA expression, and immu-nohistochemical staining results of peroxisome proliferator-activated receptor alpha (PPARa) and peroxisome prolifera-tor-activated receptor gamma coactivator 1-alpha (PGC1a) in the PC pretreatment groups were significantly upregulated - compared with the IR group in a dose-dependent manner. Conclusions: PC pretreatment suppressed inflammation, apoptosis, and autophagy via the PPAR-a signaling pathway to protect against IRI of the liver in mice.