From the Division of Gastroenterology, Department of Internal Medicine.
Clinical Research Institute.
Pancreas. 2020 Feb;49(2):281-289. doi: 10.1097/MPA.0000000000001488.
The aim of this study was to investigate the effects of eupatilin on protein kinase D1 (PKD1) and nuclear factor kappa B (NF-κB) signaling pathways in cerulein-induced in vitro pancreatitis.
We used collagenase digestion to isolate pancreatic acinar cells from male C57BL/6 mice. In vitro acute pancreatitis was induced by treatment with a supramaximal dose of cerulein. Eupatilin was pretreated before stimulation with cerulein.
Eupatilin significantly reduced cerulein-induced amylase release in pancreatic acini. Eupatilin treatment downregulated cerulein-induced expression of interleukin (IL)-1β, IL-6, and CC chemokine ligands 2 and 5, but it upregulated expression of IL-4 and IL-10. We demonstrated that eupatilin pretreatment attenuated cerulein-induced necrosis in isolated pancreatic acinar cells. This effect of eupatilin was confirmed by lactic dehydrogenase assay, fluorescence-activated cell sorting analysis, and cytopathologic analysis. Eupatilin inhibited cerulein-induced activation of PKD1/NF-κB and the nuclear translocation of NF-κB.
Our data demonstrated that eupatilin is a potential therapeutic candidate for the treatment of pancreatitis through its ability to reduce cellular necrosis and inflammatory responses by inhibition of the PKD1/NF-κB signaling pathway.
本研究旨在探讨白杨素对雨蛙肽诱导的体外胰腺炎中蛋白激酶 D1（PKD1）和核因子 kappa B（NF-κB）信号通路的影响。
我们使用胶原酶消化法从小鼠胰腺分离腺泡细胞。用雨蛙肽刺激建立体外急性胰腺炎模型。用雨蛙肽刺激前用白杨素进行预处理。
白杨素显著降低了雨蛙肽诱导的胰腺腺泡细胞中淀粉酶的释放。白杨素处理下调了雨蛙肽诱导的白细胞介素（IL）-1β、IL-6、CC 趋化因子配体 2 和 5 的表达，但上调了 IL-4 和 IL-10 的表达。我们证明了白杨素预处理可减轻雨蛙肽诱导的分离胰腺腺泡细胞坏死。通过乳酸脱氢酶测定、荧光激活细胞分选分析和细胞病理分析证实了白杨素的这种作用。白杨素抑制了雨蛙肽诱导的 PKD1/NF-κB 激活和 NF-κB 的核转位。
我们的数据表明，白杨素通过抑制 PKD1/NF-κB 信号通路，减少细胞坏死和炎症反应，可能成为治疗胰腺炎的潜在治疗候选药物。
