趋化因子MCP-1、MIP-2在急性胰腺炎相关肺损伤中的作用

Role of MCP-1 and MIP-2 in the pathogenesis of acute pancreatitis-associated lung injury

目的探讨趋化因子单核细胞趋化蛋白-1（MCP-1）与巨噬细胞炎性蛋白-2（MIP-2）在急性胰腺炎相关肺损伤早期发病机制中的作用。方法20只SD大鼠随机分为假手术组（SO组）、急性坏死性胰腺炎（ANP）3h、6h、12h组。采用4％牛磺胆酸钠胰胆管逆行注射制备ANP动物模型。检测血淀粉酶、肺湿／干重比，观察肺病理组织学改变，采用逆转录实时定量PCR检测肺组织中MCP-1与MIP-2mRNA的表达，同时经免疫组化检测肺组织中MCP-1与MIP-2蛋白的表达。所有数据以（x^-±s）表示，通过SPSS11．5统计软件处理。组间比较采用单因素方差分析，P〈0．05为差异具有统计学意义。两变量之间采用直线相关分析。结果与SO组相比，ANP各组随病变的加重，血清淀粉酶、肺湿／干重比逐渐增加[（5674±587），（74724-1013），（12554±1858）；（4．57±0．30），（6．47±0．52），（6．99±0．82），P〈0．01]，肺组织中MCP-1与MIP-2mRNA表达逐渐上调[（0．2545±0．0102），（0．3893±0．0282），（0．6040±0．0343）；（0．3997±0．0387），（0．5952±0．0330），（0．8502±0．0598），P〈0．05]，且与肺组织病理学改变呈正相关（r=0．86，0．78，P〈0．05）。免疫组化也显示肺组织中MCP-1与MIP-2蛋白水平随ANP时间的进展呈不断升高的趋势。结论趋化因子MCP-1与MIP-2在大鼠急性坏死性胰腺炎早期肺组织中即有表达，MCP-1与MIP-2在急性胰腺炎相关肺损伤早期发病机制中可能具有重要作用。

Objective To explore the potential role of cytokines-monocyte chemotactic protein-1 （MCP-1 ） and macrophage inflammatory protein-2 （MIP-2） in acute pancreatitis-associated lung injury. Method Twenty Sprague-Dawley rats were randomly divided into four groups： sham-operation （SO） group, acute necrotizing pancreatits （ANP） 3 h, 6 h, 12 h group. ANP were induced by retrograde injection 4% sodium taurocholate into the bilipancreatic duct. The activity of serum amylase and the wet and dry tissue weight ratio was determined. Pathological changes of the lung were observed. The expression of MCP-1 mRNA and MIP-2 mRNA were analyzed by real-time RT-PCR. The content of MCP-1 and MIP-2 proteins in lung tissue were examined by immunohistochemistry. Results Compared with that in SO group, serum amylase and wet/dry ratio of lungs increased greatly with the progress of acute pancreatitis （AP） [ （5674 ± 587）, （7472 ± 1013）, （12554 ± 1858）; （4.57±0.30）, （6.47±0.52）, （6.99±0.82）, P〈0.01] . The expression of MCP-1 and MIP-2 mRNA of lungs in ANP groups were all increased greatly [ （0.2545 ± 0.0102, （0.3893 ± 0.0282）, （0.6040 ±0.0343）; （0.3997±0.0387）, （0.5952±0.0330）, （0.8502±0.0598）, P〈0.05 or0.01） ]. Following the induction of ANP, the expression of MCP-land MIP-2 mRNA were both up-regulated, which was significantly correlated with the pathological changes of lung injury （ r = 0.86 and 0.78, respectively, P 〈 0.05 ）. Immunohistochemistry also confirmed the upexpression of proteins of MCP-1 and MIP-2 in tne lungs. Conclusions The chemokines MCP-1 and MIP-2 of lung are expressed at the early stage of acute necrotizing pancreatitis. Both might play an important role in the pathogenesis of acute pancreatitis-associated lung injury.