Affiliation:
1. Department of General Surgery Unit‐4 The Second Affiliated Hospital of Xi'an Jiaotong University Xi'an China
2. Department of Hepatobiliary Surgery The First Affiliated Hospital of Xi'an Jiaotong University Xi'an China
Abstract
AbstractIntroductionIschemia‐reperfusion (I/R) injury, resulting from blood flow interruption and its subsequent restoration, is a prevalent complication in liver surgery. The liver, as a crucial organ for carbohydrate and lipid metabolism, exhibits decreased tolerance to hepatic I/R in patients with diabetes mellitus (DM), resulting in a significant increase in hepatic dysfunction following surgery. This may be attributed to elevated oxidative stress and inflammation. Our prior research established sinomenine's (SIN) protective role against hepatic I/R injury. Nevertheless, the impact of SIN on hepatic I/R injury in DM rats remains unexplored.Objective and MethodsThis study aimed to investigate the therapeutic potential of SIN in hepatic I/R injury in DM rats and elucidate its mechanism. Diabetic and hepatic I/R injury models were established in rats through high‐fat/sugar diet, streptozotocin injection, and hepatic blood flow occlusion. Liver function, oxidative stress, inflammatory reaction, histopathology, and Nrf‐2/HO‐1 signaling pathway were evaluated by using UV spectrophotometry, biochemical assays, enzyme‐linked immunosorbent assay, hematoxylin‐eosin staining, and Western blot analysis.ResultsHigh‐dose SIN (300 mg/kg) significantly attenuated hepatic I/R injury in DM rats, reducing serum activities of ALT and AST, decreasing the AST/ALT ratio, enhancing tissue contents of SOD and GSH‐Px, suppressing the levels of TNF‐α and IL‐6, improving the liver histopathology, and activating Nrf‐2/HO‐1 signaling by promoting Nrf‐2 trans‐location from cytoplasm to nucleus. Low‐dose SIN (100 mg/kg) was ineffective.ConclusionsThis study demonstrates that high‐dose sinomenine's mitigates hepatic I/R‐induced inflammation and oxidative stress in diabetes mellitus (DM) rats via Nrf‐2/HO‐1 activation, suggesting its potential as a preventive strategy for hepatic I/R injury in DM patients.