Ishibashi Toshiaki, Zhao Haifeng, Kawabe Ken, Oono Takamasa, Egashira Kensuke, Suzuki Koichi, Nawata Hajime, Takayanagi Ryoichi, Ito Tetsuhide
Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
J Gastroenterol. 2008;43(1):79-85. doi: 10.1007/s00535-007-2126-9. Epub 2008 Feb 24.
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).
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.
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 48 h after disease onset. Histopathological changes of pancreas and lungs were also improved by mMCP-1.
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.
单核细胞趋化蛋白-1（MCP-1）已被证明可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找可能的治疗方法，我们评估了含有显性负性突变MCP-1基因（mMCP-1）的质粒表达载体的效果。
采用两种急性胰腺炎大鼠模型，一种使用雨蛙素（用于轻度胰腺炎），另一种使用5%牛磺胆酸和胰蛋白酶的混合物（用于重度胰腺炎）。在诱导急性胰腺炎后6小时，无论是否注射mMCP-1，均测定血清淀粉酶水平、细胞因子水平以及胰腺的形态学评估。还评估了生存率。
注射mMCP-1可显著减轻重度胰腺炎。mMCP-1降低了血清淀粉酶、IL-6、IL-10和LDH水平，并提高了疾病发作后48小时的生存率。胰腺和肺部的组织病理学变化也因mMCP-1而得到改善。
MCP-1似乎参与了重度急性胰腺炎的进展。我们的数据表明，MCP-1是治疗急性胰腺炎的一个潜在治疗靶点。
