巨噬细胞移动抑制因子在急性坏死性胰腺炎肺损伤中的表达及白介素-10的干预作用

Expression of macrophage migration inhibitory factor in experimental acute necrotizing pancreatitis lung tissue and the therapeutic effect of interleukin-10

目的探讨巨噬细胞移动抑制因子(MIF)在实验性急性坏死性胰腺炎(ANP)肺损伤发病机制中的作用以及ANP早期应用抗炎细胞因子白介素-10(IL-10)对肺组织的保护作用。方法92只大鼠随机分为对照组、ANP组和IL-10干预组,腹腔注射左旋-精氨酸制作ANP模型,干预组于末次精氨酸注射后第2、5及8h腹腔内注射IL-1010ku。各组再分4、12、24和3h点。观察并比较ANP组与IL-10干预组胰腺、腹腔及肺的大体及组织学改变,检测各组血清MIF水平以及肺组织的MIF表达。结果ANP时MIF明显升高,应用IL-10干预后各时点血清MIF明显下降(P<0.05)。正常对照大鼠肺组织的支气管上皮细胞及肺泡细胞MIF仅为弱表达,ANP时肺组织MIF阳性细胞数增加、染色明显增强,IL-10干预组的肺组织病变程度较ANP组明显减轻。结论ANP时MIF明显升高,肺组织MIF表达明显增强,提示MIF参与了大鼠ANP相关肺损伤的发病;IL-10对血清及肺组织的MIF水平有抑制作用,可减轻实验性ANP相关肺损伤的损害程度,早期给药对肺组织有保护作用。

[Objective] To investigate the expression of macrophage migration inhibitory factor （MIF in rat lung tissue with acute necrotizing pancreatitis, and to assess the effectiveness of anti-inflammatory eytokine IL-10 on the activity of MIF. [Methods] 92 SD male rats were randomly divided into control group （group C, n =24）, acute panereatitis group （group A, n =36） and IL-10 intervention group （group I, n =32）. In group A, rats were injected in- traperitoneally with 6% L-Arginine （3×1.0 mg/g） three times in an interval of 1 hour for ANP. In group C, rats received the same amount of saline at the same time instead. In group I, rats were injected intraperitoneally with IL-10（10 kU） after induction 2、5 and 8 hour. Animals were killed at 4, 12, 24 and 36 hours after the last L-Arginine injection. MIF levels in serum, pancreas and lung were determined by ELISA or immunohistoehemistry. When brown-yellow granules were observed in cytoplasm of cell, it was regarded as MIF expression positive. [Results] Serum MIF levels were early increased after the induction of ANP and remained high level. Serum MIF levels in group A were increased significantly, and serum MIF levels in group I were lower than in group A. Weakly positive immunostaining was observed in lung tissue in group C. The staining was increased in lung tissue in group A, but the staining in group I was weaker than in group A. [Conclusions] Serum MIF levels were up-regulated markedly early in ANP, and MIF positive expression in lung was increased too. These results suggest a role of MIF in the pathogenesis of ANP associated with lung injury. Interleukin-10 can inhibit the activation of MIF, and prevent the pulmonary histologic damage in Arginine-indueed ANP.