Involvement of thrombopoietin in acinar cell necrosis in L-arginine-induced acute pancreatitis in mice.
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.
Department of Gastroenterology, The First People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Jiaqing
J
Shen
Rong
R
Wan
Guoyong
G
Hu
Feng
F
Wang
Jie
J
Shen
Xingpeng
X
Wang
D061354:Acinar Cells / Q000378:metabolism* / Q000473:pathology; D000681:Amylases / Q000097:blood / Q000378:metabolism; D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001120:Arginine; D007150:Immunohistochemistry; D007770:L-Lactate Dehydrogenase / Q000097:blood / Q000378:metabolism; D008049:Lipase / Q000097:blood / Q000378:metabolism; D055370:Lung Injury / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009336:Necrosis; D010179:Pancreas / Q000378:metabolism* / Q000473:pathology; D019283:Pancreatitis, Acute Necrotizing / Q000097:blood* / Q000139:chemically induced / Q000473:pathology; D009195:Peroxidase / Q000097:blood; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D013926:Thrombopoietin / Q000097:blood* / Q000235:genetics / Q000276:immunology; D013997:Time Factors; D014867:Water / Q000378:metabolism
D000906:Antibodies; D018809:Proliferating Cell Nuclear Antigen; D011994:Recombinant Proteins; D014867:Water; D013926:Thrombopoietin; D001120:Arginine; D007770:L-Lactate Dehydrogenase; D009195:Peroxidase; D008049:Lipase; D000681:Amylases