Protective Effect of Alprostadil on Acute Pancreatitis in Rats via Inhibiting Janus Kinase 2 (JAK2)/STAT3 Signal Transduction Pathway
Shuke Fei, Wei Li, Lei Xiang, Xuewen Xie, Liang Zhang
Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital of University of South China, Hengyang, Hunan, China (mainland)
Med Sci Monit 2019; 25:7694-7701
Alprostadil can inhibit inflammation and reduce inflammation-related injury in many inflammatory diseases. However, the anti-inflammatory effect of alprostadil in decreasing acute pancreatitis (AP) injury remains unknow. This study aimed to investigate the possible protective effects and mechanism of alprostadil against AP in rats.
MATERIAL AND METHODS: Forty healthy Sprague‑Dawley rats were randomly divided into a control group, an AP group, an AP-alprostadil group, an AP-AG490 group, and an AP-(alprostadil+AG490) group. An animal model of acute pancreatitis was established. The pathological changes of the pancreases in each group were observed. We assessed levels of malondialdehyde (MDA), superoxide dismutase (SOD), and myeloperoxidase (MPO), as well as serum IL-1ß, IL-6, IL-10, and TNF-alpha. TUNEL assay was used to detect apoptosis of pancreatic cells. The proteins p-Jak2 and p-Stat3 were investigated by Western blot.
RESULTS: Compared with the control group, pancreatic pathological score, pancreatic apoptosis, MDA, MPO, serum IL-1ß, IL-6, and TNF-alpha levels were significantly higher in the AP group, and SOD levels were significantly decreased. Compared with the AP group, after treatment with alprostadil, AG490, and alprostadil+AG490, respectively, the pancreatic pathological score, apoptosis, MDA, MPO, serum IL-1ß, IL-6, and TNF-alpha were significantly decreased in AP rats, while SOD levels were significantly increased. The protein levels of p-JAK2 and p-STAT3 were significantly upregulated in the AP group compared with the control group, and the protein levels of p-JAK2 and p-STAT3 after treatment with alprostadil, AG490, and alprostadil+AG490 were significantly decreased, and the effect of alprostadil+AG490 was the strongest.
CONCLUSIONS: Alprostadil can reduce pancreatic tissue damage, delay pancreatic cell apoptosis, and reduce inflammation and anti-oxidative stress by inhibiting the JAK2/STAT3 signal pathway, thus protecting the pancreas.
Keywords: Alprostadil, Janus Kinase 2, Pancreatitis, Signal Transduction, STAT3 Transcription Factor