早期阻断MCP-1对实验性急性坏死性胰腺炎的作用

Effect on blockade of MCP 1 in early course of experimental acute necrotizing pancreatitis

目的 探讨趋化因子MCP-1对实验性急性坏死性胰腺炎（ANP）及其并发症的影响。方法60只SD大鼠按数字表法分为假手术组、ANP组和MCP-1多抗干预组（干预组），各20只。采用3．5％牛黄胆酸钠制备ANP模型，干预组于制模后0、6h皮下注射抗MCP-1多抗。观察血清淀粉酶、MCP-1、D-乳酸含量变化；观察胰腺、肺、小肠组织病理改变及MCP-1mRNA的表达；检测胰腺MCP-1蛋白表达；检测肺、小肠髓过氧化酶（MPO）含量。结果干预组12h的血淀粉酶、MCP-1、D-乳酸含量分别为（4666±412）U／L、（39．53±8．25）pg/ml和（6．3±2．2）mg／L，均显著低于ANP组的（9611±363）U／L、（63．42±9．32）pg／ml和（9．3±2．1）mg／L（P值均〈0．05）；胰腺、肺、小肠组织MCP-1mRNA表达量分别为0．4314-0．009、0．211±0．018和0．442±0．017，均显著低于ANP组的0．624±0．010、0．523±0．019和0．569±0．024（P值均〈0．05）；胰腺MCP-1蛋白表达评分为2．0±0．1，显著低于ANP组的4．0±0．2（P〈0．05）；肺、小肠组织MPO含量分别为（11．1±3．0）U／g组织和（19．2±2．0）U／g组织，均与ANP组的（39．2±3．1）U／g组织和（13．1±2．1）U／g组织有显著差异（P值均〈0．05）。结论早期阻断MCP-1不但可以减轻急性胰腺炎病理损伤，而且能减轻急性肺损伤和肠屏障的损伤程度。

Objective To investigate the potential role of MCP-1/CCL2 in experimental acute necrotizing pancreatitis （ANP） and complications. Methods 60 SD male rats were randomly divided into 3 groups ： sham operation group （ n = 20 ）, ANP group （ n = 20 ） and MCP-1 group （ n = 20 ）. ANP model was induced by retrograde infusion of 3.5% sodium taurocholate, MCP-1 group received subcutaneous injection of MCP-1 antibody 0 h and 6 h after ANP induction. The serum levels of amylase, MCP-1, D-lactic acid, histological changes and the expression of MCP-1 mRNA of lung, small intestine and pancreas, the expression of MCP-1 protein in pancreas, MPO levels of small intestine MPO were determined. Results The serum levels of amylase, MCP-1, D-lactic acid in MCP-1 group at 12 h were （4666 ±412）U/L, （39.53 ± 8.25）pg/ml and （6.3 ± 2.2）mg/L, which were significantly lower than those in ANP group [ （9611 ± 363 ）U/L, （63.42 ±9.32） pg/ml, （9.3 ±2.1 ） mg/L, P 〈 0.05 ） ] ; the expression of MCP-1 mRNA in pancreas, small intestine and lung were 0. 431 ±0. 009, 0.211± 0. 018 and 0.442 ±0. 017, which were significantly lower than those in ANP group [ （0. 624 ± 0. 010, 0. 523 ±0. 019 and 0. 569±0. 024, P 〈 0.05 ） ] ; the expression of MCP-1 protein in pancreas was 2.0 ±0. 1, which was significantly lower than that in ANP group （ 4.0 ± 0.2, P 〈 0.05）. Lung and small intestine MPO were （11.1 ±3.0）U/g and （19.2±2.0）U/g, which were significantly lower than those in ANP group [ （39.2± 3.1 ） U/g and （ 13.1± 2.1 ） U/g, P 〈 0.05 ]. Conclusions Early blockade of MCP-1 not only attenuates the severity of ANP, but also decreases the degree of acute lung injury and intestine barrier dysfunction.