Blocking of monocyte chemoattractant protein-1 (MCP-1) activity attenuates the severity of acute pancreatitis in rats
Blocking of monocyte chemoattractant protein-1 (MCP-1) activity attenuates the severity of acute pancreatitis in rats
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DOI：
10.1007/s00535-007-2126-9
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发表时间：
2008-01-01
影响因子：
6.3
通讯作者：
Ito, Tetsuhide
中科院分区：
文献类型：
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作者：
Ishibashi, Toshiaki;Zhao, Haifeng;Ito, Tetsuhide
背景。单核细胞趋化蛋白-1 (MCP-1) 已被证明会影响包括胰腺炎在内的各种炎症性疾病的进展。为了研究MCP-1在急性胰腺炎中的作用并寻求可能的治疗手段，我们评估了含有显性失活突变体MCP-1基因（mMCP-1）的质粒表达载体的效果。方法。采用两种急性胰腺炎大鼠模型，使用雨蛙素（用于轻度胰腺炎）或 5% 牛磺胆酸和胰蛋白酶的混合物（用于严重胰腺炎）。在注射或不注射mMCP-1的急性胰腺炎诱导后6小时，测定血清淀粉酶水平和细胞因子水平以及胰腺的形态学评估。还评估了存活率。结果。注射 mMCP-1 可显着减少重症胰腺炎。 mMCP-1降低血清淀粉酶、IL-6、IL-10和LDH水平，并提高发病后48小时的存活率。 mMCP-1也改善了胰腺和肺的组织病理学变化。结论。 MCP-1 似乎参与了严重急性胰腺炎的进展。我们的数据表明 MCP-1 是治疗急性胰腺炎的候选靶点。
Background. Monocyte chemoattractant protein-1 (MCP-1) has been shown to affect the progression of various inflammatory disorders, including pancreatitis. To investigate the role of MCP-1 in acute pancreatitis and to seek possible therapeutic means, we evaluated the effect of a plasmid expression vector containing a dominant-negative mutant MCP-1 gene (mMCP-1). Methods. Two rat models of acute pancreatitis were employed that used either cerulein (for mild pancreatitis) or a mixture of 5% taurocholic acid and trypsin (for severe pancreatitis). At 6 h after induction of acute pancreatitis with or without injection of mMCP-1, serum amylase levels and cytokine levels, as well as morphological evaluation of the pancreas, were determined. Survival rates were also evaluated. Results. Severe pancreatitis was significantly reduced by mMCP-1 injection. mMCP-1 decreased serum levels of amylase, IL-6, IL-10, and LDH, and improved the survival rate 48h after disease onset. Histopathological changes of pancreas and lungs were also improved by mMCP-1. Conclusions. MCP-1 appears to be involved in the progression of severe forms of acute pancreatitis. Our data suggested that MCP-1 is a candidate as a therapeutic target to treat acute pancreatitis.