Effects of leonurine on the improvement of rats with severe acute pancreatitis by regulating HMGB1/RAGE signaling pathway / 中国药房

ABSTRACT

OBJECTIVE To study the effects of leonurine on pancreatic injury in rats with severe acute pancreatitis （SAP）， and to explore its mechanism based on the high-mobility group box 1 （HMGB1）/receptor for advanced glycation end products （RAGE） signaling pathway. METHODS SAP rat model was constructed by injecting 5% sodium taurocholate into the bile duct of the pancreas. Model rats were randomly divided into model group， low dose leonurine group （8 mg/kg）， high dose leonurine group （16 mg/kg）， HMGB1 overexpression group （8 μg/kg）， and high dose leonurine+HMGB1 overexpression group （16 mg/kg+8 μg/kg）， with 14 rats in each group. Another 14 rats were selected as the sham operation group. Rats in each group were injected with corresponding drugs or normal saline via abdominal cavity or tail vein once a day for 5 consecutive days. After the last administration， the levels of serum amylase （AMS） and lipase （LPS） were detected； the pathological injury of pancreatic tissue was observed； the levels of tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， malondialdehyde （MDA） and superoxide dismutase （SOD）， mRNA and protein expressions of HMGB1 and RAGE in pancreatic tissues were detected. RESULTS Compared with model group， the structure of pancreatic tissue in rats gradually recovered in low and high dose leonurine groups； inflammatory cell infiltration gradually decreased； the pathological injury score and the levels of AMS， LPS， TNF-α， IL-6， MDA， the mRNA and protein expressions of HMGB1 and RAGE were significantly decreased， while the SOD levels were significantly increased （P＜0.05）. The high dose leonurine group showed more significant improvement （P＜0.05）； the pathological damage of pancreatic tissue in the HMGB1 overexpression group worsened， and except for a decrease in SOD levels， all other quantitative indicators increased significantly （P＜0.05）. Overexpression of HMGB1 could reduce the improvement effect of high dose leonurine on the above indexes in SAP rats （P＜0.05）. CONCLUSIONS Leonurine may alleviate pancreatic injury， inflammation and oxidative stress in pancreatic tissue of rats with SAP by inhibiting the HMGB1/RAGE signaling pathway.