Grape Seed Proanthocyanidin Protects Liver Against Ischemia/reperfusion Injury By Attenuating Endoplasmic-reticulum Stress The First Affiliated Hospital Of Nanjing Medical University General Surgery

To explore the modulation effect of grape seed proanthocyanidin(GSP) on protectin liver ischemia/reperfusion(I/R) injury and the alleviation of endoplasmic reticulum(ER) stress. Male Sprague–Dawley rats(220g – 250g) were divided into three groups, namely, sham, I/R, and GSP groups(n=8 in each group). A liver I/R(70%) model was established and reperfused for 6h. Prior to reperfusion, the GSP group was administered with GSP(100mg/kg) for 15 days, and liver histology was then investigated. Serum aminotransferase and inflammatory mediators coupled with superoxide dismutase(SOD) and methane dicarboxylic aldehyde(MDA) were detected. Western blot was conducted to analyze the expression of glucose-regulated protein78(GRP78), C/EBP(CCAAT/enhancer binding protein) homologous protein(CHOP), activating transcription factor-4(ATF4), inositol-requiring enzyme-1(IRE1),(procaspase-12), and NF-κb. Apoptotic cells were detected by TUNEL staining. We found that the serum aminotransferase, apoptotic cells, and Suzuki scores decreased in the GSP group compared with the I/R group. The MDA level was decreased in the GSP group, but the SOD level was reversed. Similarly, GSP downregulated the pro-inflammatory factors and upregulatedthe levels of anti-inflammatory factors. Western blot data showed that GSP increased GRP78 expression and suppressed CHOP, ATF4, IRE1, procaspase-12, and NF-κb expression compared with the I/R group.In summary, GSP possesses anti-oxidation,anti-inflammatory, and anti-apoptosis effects by relieving ER stress through regulating relative signaling ways to achieve the defensive effect on liver injury.