SEW2871 Alleviates the Severity of Caerulein-Induced Acute Pancreatitis in Mice.
SEW2871 Alleviates the Severity of Caerulein-Induced Acute Pancreatitis in Mice.
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SEW2871 减轻雨蛙素诱发的小鼠急性胰腺炎的严重程度。
DOI：
10.1248/bpb.b15-00043
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发表时间：
2015-07
期刊：
影响因子：
--
通讯作者：
Li, Jieshou
中科院分区：
文献类型：
--
作者：
Tong, Zhihui;Li, Weiqin;Li, Ning;Li, Jieshou
1-磷酸鞘氨醇1型受体（S1P1）激动剂具有抑制淋巴细胞流出的潜力，并已被证明对某些急性炎症性疾病具有保护作用。然而，S1P1激动剂对急性胰腺炎（AP）的价值仍不清楚。本研究的目的是探讨 S1P1 选择性激动剂 SEW2871 对雨蛙素诱导的小鼠 AP 的影响。 AP是通过每小时间隔腹膜内注射8次雨蛙素(50μg/kg/h)来诱导的。在第一次腹膜内注射雨蛙素后0小时和12小时，通过管饲法施用SEW2871，剂量为20mg/kg。 24小时处死小鼠。评估 AP 的严重程度、血清淀粉酶和脂肪酶活性、血清细胞因子水平、胰髓过氧化物酶 (MPO) 活性、血液中 CD45+CD4+T 淋巴细胞、胰腺中 CD4+T 细胞浸润以及促炎细胞因子的产生。此外，还评估了胰腺中信号转导子和转录激活子（STAT）3和磷酸-STAT3（p-STAT3）的表达。结果显示，服用SEW2871可通过降低血清胰酶活性和细胞因子水平、降低胰腺MPO活性、消除血液中CD4+CD45+T淋巴细胞以及减少胰腺中CD4+T细胞浸润来改善AP的严重程度。此外，促炎细胞因子 mRNA 和 p-STAT3 的表达也被 SEW2871 治疗抑制。这些结果表明SEW2871治疗减轻了雨蛙素诱导的小鼠AP的严重程度，这可能为AP治疗提供新的治疗方法。
Sphingosine-1-phosphate type-1 receptor (S1P1) agonists have the potential to inhibit the egress of lymphocytes, and have been demonstrated to provide protective effects on some acute inflammatory diseases. However, the value of S1P1 agonists on acute pancreatitis (AP) remains unclear. The aim of this study was to explore the effect of SEW2871, a S1P1-selective agonist, on caerulein-induced AP in mice. AP was induced by giving eight intraperitoneal injections of caerulein (50 µg/kg/h) at hourly intervals. SEW2871 was administered by gavage, at a dose of 20 mg/kg, at 0 h and 12 h after the first intraperitoneal injection of caerulein. The mice were sacrificed at 24 h. Severity of AP, serum amylase and lipase activity, levels of serum cytokines, pancreatic myeloperoxidase (MPO) activity, CD45+CD4+ T lymphocytes in blood, CD4+ T cell infiltration in the pancreas, and proinflammatory cytokine production were assessed. Furthermore, the expression of signal transducer and activator of transcription (STAT) 3 and phospho-STAT3 (p-STAT3) in the pancreas was also evaluated. The results revealed that the administration of SEW2871 ameliorated the severity of AP, by a reduction of serum pancreatic enzyme activity and levels of cytokines, decreased pancreatic MPO activity, depletion of CD4+CD45+ T lymphocytes in the blood and a reduction of CD4+ T cell infiltration in the pancreas. Furthermore, the expression of proinflammatory cytokines mRNA and p-STAT3 were also suppressed by SEW2871 treatment. These results suggest that SEW2871 treatment attenuates the severity of caerulein-induced AP in mice, which may provide a new therapeutic approach for AP therapy.
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影响因子：
5.8
作者：
J. Yu;K. Kim;Hyeyoung Kim
通讯作者：
J. Yu;K. Kim;Hyeyoung Kim
影响因子：
2.9
作者：
Okamoto, T;Yamada, T;Itoh, M
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Itoh, M
影响因子：
3
作者：
Jacob, Tony G.;Raghav, Rahul;Roy, Tara S.
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Roy, Tara S.
影响因子：
29.4
作者：
Demols, A;Le Moine, O;Devière, J
通讯作者：
Devière, J
急性胰腺炎的病理生理学
影响因子：
2.6
作者：
J. Trapnell
通讯作者：
J. Trapnell