Konończuk Tomasz, Łukaszuk Bartłomiej, Mikłosz Agnieszka, Chabowski Adrian, Żendzian-Piotrowska Małgorzata, Kurek Krzysztof
From the Departments of Hygiene, Epidemiology and Ergonomics.
Physiology, and.
Pancreas. 2018 Aug;47(7):898-903. doi: 10.1097/MPA.0000000000001086.
Acute pancreatitis (AP) is a common and severe gastrointestinal inflammatory disease with poorly understood pathogenesis. We adopted cerulein-induced pancreatitis, a well-established rat model shearing similarities with human AP, to determine the disease background. Special interest was placed on sphingolipids, because their signaling pathways are involved in many pathological states including hepatic steatosis, heart infarction, or pancreatic origin type 1 diabetes.
Sphingolipid levels in the blood and pancreas were determined by the means of chromatography (thin-layer and high-performance liquid chromatography).
We found that AP leads to activation of ceramide de novo synthesis pathway, as evidenced by a significant increment in sphinganine, that is, ceramide synthesis precursor, content (+3.8-fold). Surprisingly, despite the reported growth in sphinganine concentration, we observed a reduced (-38%) ceramide level in the pancreas of rats with AP. The results could be explained by subsequent hydrolysis of ceramide to other secondary messengers, that is, sphingosine (+4-fold) or sphingosine-1-phosphate (+3-fold).
Because it is known that sphingosine-1-phosphate and some of its analogs could have a protective role against AP complications, our findings may contribute to elaboration of new therapeutic strategies in the management of this severe medical condition.
急性胰腺炎（AP）是一种常见且严重的胃肠道炎症性疾病，其发病机制尚不清楚。我们采用了雨蛙肽诱导的胰腺炎，这是一种与人类AP有相似之处的成熟大鼠模型，以确定疾病背景。特别关注鞘脂类，因为它们的信号通路参与了许多病理状态，包括肝脂肪变性、心肌梗死或胰腺起源的1型糖尿病。
通过色谱法（薄层和高效液相色谱法）测定血液和胰腺中的鞘脂水平。
我们发现AP导致神经酰胺从头合成途径的激活，鞘氨醇（即神经酰胺合成前体）含量显著增加（+3.8倍）证明了这一点。令人惊讶的是，尽管报道鞘氨醇浓度有所增加，但我们观察到AP大鼠胰腺中的神经酰胺水平降低了（-38%）。这一结果可以通过神经酰胺随后水解为其他第二信使，即鞘氨醇（+4倍）或鞘氨醇-1-磷酸（+3倍）来解释。
由于已知鞘氨醇-1-磷酸及其一些类似物可能对AP并发症具有保护作用，我们的发现可能有助于制定针对这种严重疾病的新治疗策略。
