LXA_4对ANP诱发SIRS过程中NF-κB、ICAM-1表达的影响

Effect of LXA_4 on the Expression of NF-κB and ICAM-1 in the Process of SIRS Induced by ANP

目的探讨脂氧素A4抑制急性坏死性胰腺炎诱发SIRS的机制。方法健康雄性SD大鼠72只随机分为假手术组、ANP组和脂氧素A4(LXA4)干预组,分别采用等量生理盐水、LXA4(0.1mg/kg)间隔8h经阴茎背静脉注射,并分别于4、12、24h每组活杀8只大鼠,测定胰腺组织Schmidt病理评分、NF-ΚB、ICAM-1的表达水平。结果 (1)与假手术组比较,胰腺炎组、LXA4干预组的Schmidt胰腺病理评分有显著升高(P<0.01);LXA4干预组Schmidt胰腺病理评分在12、24h较胰腺炎组低(P<0.05)。(2)假手术组ICAM-1表达阴性,胰腺炎组、LXA4干预组随着病变进展,其反映ICAM-1表达相对强度的累积光密度值(IOD)逐渐上升(P<0.01);在4、12、24h等3个时点,LXA4干预组的IOD值较比SAP组均有显著下降(P<0.01)。(3)假手术组NF-κB P65蛋白阴性;ANP组NF-κB胞核阳性表达率为59.1%(13/22),显著高于LXA4干预组的4.3%(1/23),差异具有统计学意义(P<0.01)。结论 (1)LXA4在ANP诱发SIRS过程中确能抑制ICAM-1的表达。(2)LXA4抑制ANP诱发SIRS可能是通过抑制NF-κB的细胞信号传导途径来实现的。

Objective To study the mechanism of LXA4 to inhibit the SIRS induced by ANP in rats. Methods Seventy - two healthy SD rats were randomly divided into three groups ：sham group, SAP group and LXA4 group. Equal amount of physiological saline and LXA4 （0. lmg/kg）were injected via the dorsal penis vein separately. Each group was divided into 3 small subgroups according to the time point 4, 12, 24hours after the operation. Then the level of ICAM - 1 and NF -κB in pancreatic tissues were measured by immuno- histoehemistry（IHC） ,pancreas pathologic grade were also determined. Results （ 1 ） Among the three groups, levels of pathologic score of the SAP group and LXA4 group showed increase significantly comparing with those of the sham group（ P 〈 0.01 ） ; On the time points of 12h and 24h, levels of pathologic score in LXA4 group decreased significantly comparing with SAP group （P 〈 0.05 ）. （2）The expression of ICAM - 1 in sham group was negative. Along with the progress of pathological changes, the IOD that reflect the relative intensity of ICAM - 1 in SAP group and LXA4 group rise gradually（P 〈 0.01 ） ; On the three time points, levels of IOD in LXA4 group decreased significantly comparing with SAP group（ P 〈 0.01 ）. （3）The expression of NF-κB P65 in sham group was negative. Nuclear positive rate of NF - KB P65 in SAP group was 59.1% （13/22）. It was apparently higher than that in LXA4 group which was 4.3% （ 1/23 ）. Conclusion （ 1 ） LXA4 can really decrease the levels of ICAM - 1 in pancreatic tissues in the process of SIRS induced by ANP. （2） The mechanism of LXA4 to inhibit the SIRS induced by ANP in rats may be related to NF -κB. Key words Pancreatitis ; Lipoxins A4 （ LXA4 ） ; Nuclear factor-κB （ NF -κB） ; Interceller adhesion moleculer - 1 （ ICAM - 1 ）