Augmenter of liver regeneration (ALR) regulates acute pancreatitis via inhibiting HMGB1/TLR4/NF-κB signaling pathway.

This research aimed to explore the effect of augmenter of liver regeneration (ALR) in acute pancreatitis (AP) of mice and the underlying mechanism. Caerulein were given to mice to get AP models. AP mice were given saline, ALR plasmids or negative control plasmids. Then, pancreas tissues were fixed and stained for histological examination. The levels of serum amylase, serum lipase, MPO, HMGB1, TNF-alpha, IL-1 beta as well as MCP-1 were detected by ELISA assay. The mRNA levels of TLR4, p65, I kappa B alpha, iNOS, COX-2 and GAPDH were examined by RT-qPCR. The protein levels of HMGB1, TLR4, MD2, MyD88, I kappa B alpha and GAPDH were detected by western blotting. ALR decreased serum amylase as well as lipase levels and alleviated the histopathological alterations of the pancreas in AP mice. ALR decreased the MPO activity of pancreas in AP Mice. ALR decreased the HMGB1/TLR4 signaling pathway in AP Mice. ALR decreased pancreas IL-1 beta and MCP-1 in AP mice, and also decreased plasma TNF-alpha and IL-1 beta in AP mice. ALR attenuated the cerulein-caused increase in p65 mRNA and protein levels, but had no effects on mRNA and protein levels of I kappa B alpha. The AP mice significantly promoted the mRNA levels of iNOS and COX-2 that was inhibited by ALR. HNE formation was also increased in AP mice, but it was decreased by ALR. ALR alleviates acute pancreatitis by inhibiting HMGB1/TLR4/NF-kappa B signaling pathway. It is promising to alleviate the syndromes of patients with acute via targeting ALR.