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目的探讨低分子量肝素(LMWH)对重症急性胰腺炎(SAP)肺损伤的保护作用。方法 SD大鼠随机分为3组:(1)假手术对照组(S组);(2)SAP组;(3)LMWH治疗组(LT组):制成SAP模型后4h给予LMWH治疗。检测SAP,S组成模术后24h,LMWH治疗后24h的血清淀粉酶,ET-1,TNF-α,肺组织湿/干比重、形态学变化,P65基因及P65蛋白的表达,以及3d动物存活率。结果 (1)SAP组血清淀粉酶,TNF-α,ET-1水平显著高于S组和LT组(均P<0.001),LT组血清淀粉酶水平显著高于S组(P<0.05)。(2)SAP组肺组织P65mRNA及P65蛋白的表达显著高于S组和LT组(均P<0.05)。(3)SAP组肺组织湿/干比重显著高于S组和LT组(均P<0.001)。(4)SAP组可见肺泡和间质广泛水肿,肺泡有透明膜形成,肺泡组织中性粒细胞聚集成团;LT组肺泡和间质水肿和中性粒细胞聚集程度均较SAP组明显减轻,未见有透明膜形成。(5)SAP组的3d存活率(25.0%)显著低于S组(100.0%)和LT组(87.5%)(均P<0.05)。结论 LMWH通过抑制肺脏组织NF-κB的活性,下调炎症介质的表达;同时可降低ET-1水平,改善微循环;从而减轻SAP大鼠的肺损伤,提高动物生存率。
Objective To investigate the protective effect of low molecular weight heparin (LMWH) on lung injury in severe acute pancreatitis (SAP). Methods SD rats were randomly divided into three groups: (1) sham operation control group (S group); (2) SAP group; (3) LMWH treatment group (LT group): LMWH treatment was given 4 hours after SAP model was made. The levels of serum amylase, ET-1, TNF-α, lung wet / dry weight, morphological changes, P65 gene and P65 protein expression in 24h after LMWH treatment were detected, and the survival of 3d animals rate. Results The levels of serum amylase, TNF-α and ET-1 in SAP group were significantly higher than those in S group and LT group (all P <0.001). The levels of serum amylase in LT group were significantly higher than those in S group (P <0.05). (2) The expression of P65 mRNA and P65 protein in SAP group was significantly higher than that in S group and LT group (all P <0.05). (3) The wet / dry weight of lung in SAP group was significantly higher than that in S group and LT group (P <0.001). (4) Alveolar and interstitial edema were observed in the SAP group, the alveolar cells were formed in a transparent membrane and the alveolar tissue aggregated into pellets; the alveolar and interstitial edema and neutrophil aggregation in the LT group were significantly reduced compared with those in the SAP group No transparent film was formed. (5) The 3d survival rate (25.0%) in SAP group was significantly lower than that in S group (100.0%) and LT group (87.5%) (both P <0.05). Conclusion LMWH can down-regulate the expression of inflammatory mediators by inhibiting the activity of NF-κB in the lung tissue, reduce the level of ET-1, and improve microcirculation. Thus, LMWH can reduce lung injury and improve the survival rate of animals.