Department of Gastroenterology, The First People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Cytokine. 2012 Oct;60(1):294-301. doi: 10.1016/j.cyto.2012.05.005. Epub 2012 Jun 13.
Thrombopoietin (TPO) plays an important role in injuries of different tissues. However, the role of TPO in acute pancreatitis (AP) is not yet known. The aim of the study was to determine the involvement of TPO in AP. Serum TPO was assayed in necrotizing pancreatitis induced by L-arginine in mice. Recombinant TPO and anti-TPO antibody were given to mice with necrotizing pancreatitis. Amylase, lipase, lactate dehydrogenase, myeloperoxidase activity and pancreatic water content were assayed in serum and tissue samples. Pancreas and lung tissue samples were also collected for histological evaluation. Immunohistochemistry of amylase α and PCNA were applied for the study of acinar regeneration and TUNEL assay for the detection of apoptosis in the pancreas. Increased levels of serum TPO were found in necrotizing pancreatitis. After TPO administration, more severe acinar necrosis was found and blockade of TPO reduced the acinar necrosis in this AP model. Acinar regeneration and apoptosis in the pancreas were affected by TPO and antibody treatment in necrotizing pancreatitis. The severity of pancreatitis-associated lung injury was worsened after TPO treatment, but attenuated after Anti-TPO antibody treatment. In conclusion, serum TPO is up-regulated in the necrotizing pancreatitis induced by L-arginine in mice and may be a risk factor for the pancreatic acinar necrosis in AP. As a pro-necrotic factor, blockade of TPO can attenuate the acinar necrosis in AP and may be a possible therapeutic intervention for AP.
血小板生成素（TPO）在不同组织损伤中发挥重要作用。然而，TPO 在急性胰腺炎（AP）中的作用尚不清楚。本研究旨在确定 TPO 在 AP 中的作用。在小鼠的坏死性胰腺炎模型中检测了 L-精氨酸诱导的血清 TPO。给予坏死性胰腺炎小鼠重组 TPO 和抗 TPO 抗体。检测血清和组织样本中的淀粉酶、脂肪酶、乳酸脱氢酶、髓过氧化物酶活性和胰腺含水量。还收集胰腺和肺组织样本进行组织学评估。应用淀粉酶α和 PCNA 的免疫组化研究腺泡再生，并用 TUNEL 检测法检测胰腺中的细胞凋亡。在坏死性胰腺炎中发现血清 TPO 水平升高。给予 TPO 后，发现腺泡坏死更严重，而在该 AP 模型中阻断 TPO 可减少腺泡坏死。在坏死性胰腺炎中，TPO 和抗体治疗可影响胰腺的腺泡再生和凋亡。TPO 治疗后胰腺炎相关肺损伤的严重程度加重，但抗 TPO 抗体治疗后减轻。总之，在 L-精氨酸诱导的小鼠坏死性胰腺炎中，血清 TPO 上调，可能是 AP 中胰腺腺泡坏死的危险因素。作为促坏死因子，阻断 TPO 可减轻 AP 中的腺泡坏死，可能是 AP 的一种潜在治疗干预措施。
