低分子量肝素对重症急性胰腺炎肺损伤保护作用的实验研究
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吕新生E-mail:xinshenglv@hotmail.com

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湖南省医药卫生科学技术研究资助课题(y02-012)。


Study of the protective effect of low molecular weight heparin on lung injury in severe acute pancreatitis in rats
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    摘要:

    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4 h给予LMWH治疗。检测SAP,S组成模术后24 h,LMWH治疗后24 h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3 d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P65 mRNA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3 d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。

    Abstract:

    Objective:To investigate the protective efficiency of low molecular weight heparin (LMWH) on lung injury in severe acute pancreatitis (SAP).
    Methods:SD rats were randomly divided into 3 groups: (1) Sham operation (S) group,(2) SAP group,(3) LMWH treatment (LT) group:LMWH was administrated 4 hours after SAP model was constructed. The levels of serum amylase, endothelin1(ET-1), tumor necrosis factor α (TNF-α), lung wet/dry weight ratios, pulmonary morphology, the expressions of P65 mRNA and P65 protein in pulmonary specimens were detected at 1d after the models were set up, and the 3 days survival rate in each group was also observed.
    Results:(1) The levels of serum amylase, TNF-α,  ET-1 in SAP group were significantly increased than those in S group and LT group (all P<0.001), and the level of serum amylase in LT group was significantly increased than that in S group (P<0.05). (2) The expression of P65 protein and P65 mRNA in pulmonary specimens of SAP group was significantly lower than that in S group and in LT group (all P<0.05). (3)The lung wet/dry weight ratio in SAP group was significantly increased than that in S group and LT group (all P<0.001). (4)The inflammatory cells infiltration, hyaline membrane and increase of pulmonary microvascular permeability in alveoll in SAP group were significantly serere than those in LT group. (5) The 3 days survival rate in SAP group (25.0%) was significantly lower than that in S group (100.0%) and LT group (87.5%) (all P<0.05).
    Conclusions:LMWH therapy can improve the survival rate of SAP, and might be related to the amelioration of the lung injury by down-regulating the levels of cytokines release through suppressing the activity of nuclear factor kappa B and improving the pulmonary microcirculatory by down-regulating the level of serum ET-1.

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邱氟| 吕新生|黄宇琨.低分子量肝素对重症急性胰腺炎肺损伤保护作用的实验研究[J].中国普通外科杂志,2010,19(6):629-633.
DOI:10.7659/j. issn.1005-6947.2010.06.009

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  • 收稿日期:2010-01-15
  • 最后修改日期:2010-03-10
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  • 在线发布日期: 2010-06-15