基础医学与临床 ›› 2014, Vol. 34 ›› Issue (7): 891-895.

• 研究论文 • 上一篇    下一篇

藻蓝素减轻大鼠脓毒症性急性肺损伤及分子机制

张大利1,吴建华2,谢黎明1,刘双全1   

  1. 1. 南华大学附属第一医院
    2. 衡阳市第一人民医院呼吸内科
  • 收稿日期:2013-12-23 修回日期:2014-04-07 出版日期:2014-07-05 发布日期:2014-06-24
  • 通讯作者: 张大利 E-mail:nhzhangdali@163.com
  • 基金资助:
    国家自然科学基金

Molecular mechanism of C-phycocyanin in alleviation of acute lung injury in septic rats

  • Received:2013-12-23 Revised:2014-04-07 Online:2014-07-05 Published:2014-06-24
  • Supported by:
    the Chinese National Natural Science Foundation

摘要: 目的 观察藻蓝素(CPC)对脓毒症急性肺损伤大鼠的保护作用及分子机制。方法 将大鼠随机分为对照组、模型组和CPC干预组。其中模型组采用盲肠结扎穿刺建立脓毒症急性肺损伤大鼠模型。CPC干预组在模型组基础上分别腹腔注射给予20, 40和60mg/kg CPC。术后72h后获取血液及肺组织标本,检测PaO2/FiO2、肺湿干重比(W/D)、支气管肺泡灌洗液中肿瘤坏死因子(TNF)-α,白介素(IL)-1β和IL-6水平,以及肺组织中丙二醛(MDA)水平及髓过氧化物酶(MPO)活性;比色法检测血红素氧合酶(HO)-1活性,用RT-PCR检测mRNA表达。结果 与对照组相比,模型组PaO2/FiO2含量显著降低(p<0. 05),W/D比值以及MDA和MPO显著高于对照组(p<0. 05)。不同浓度CPC干预后,PaO2/FiO2进一步增高,肺湿干重、MDA和MPO水平随之降低(p<0. 05);模型组大鼠BALF中TNF-α、IL-1β和IL-6含量,HO-1活性及其mRNA表达水平增高(p<0. 05),而CPC能进一步降低TNF-α、IL-1β和IL-6含量含量,同时能增加HO-1的酶活性以及上调其mRNA水平(p均<0. 05)。此外,HO-1激动剂锡原卟啉(CoPP)处理后,能协同CPC降低TNF-α、IL-1β和IL-6含量,而HO-1抑制剂锌原卟啉(ZnPP)能进一步促进细胞因子产生(均p <0. 05)。结论:CPC可能通过上调HO-1表达,从而减轻脓毒症急性肺损伤大鼠肺部气体交换功能和炎性反应。

关键词: 藻蓝素, 脓毒症, 急性肺损伤, 血红素氧合酶1

Abstract: Objective To observe the protective effect and molecular mechanism of C-phycocyanin (CPC) on acute lung injury in septic rats. Methods Rats were randomly divided into control group, model group and CPC group. Cecal ligation and puncture was used to establish a septic acute lung injury rats (model group). For the CPC groups, septic acute lung injury rats were administrated by 20,40 and 60mg/kg of CPC by peritoneal injection. 72h after the operation, serum and lung tissue were obtained, the PaO2/FiO2, the wet to dry weight ratio, content of tumor necrosis factor (TNF)-α、interleukin (IL)-6 and IL-10 in bronchoalveolar lavage fluid, the concentration of malondialdehyde (MDA) and activity of myeloperoxidase (MPO) was analyzed. Enzymic activity of heme oxygenase (HO)-1 and its mRNA was detected by colorimetric method and RT-PCR, respectively. Results The PaO2/FiO2, the content of MDA, activity of MPO, and thewet to dry weight ratio was increased in the model group, and it was statistically significant than that in the control group (P<0.05), after CPC treatment, the level of PaO2/FiO2 increased, the wet to dry weight ratio and the content of MDA and activity of MPO decreased (P<0.05), In the medel group, TNF-α、IL-6 and IL-1β in bronchoalveolar lavage fluid was increased, HO-1 acivity and mRNA level was also increased(P<0.05). CPC could decrease the cytokines level, and upregulate HO-1 acitvity and mRNA expression. In addition, HO-1 agonist CoPP could synergize CPC to production of TNF-α、IL-6 and IL-10 1β, but HO-1 antagonist ZnPP could futher increase the cytokines production. Conclusion CPC could induce HO-1 expression, and thus relieve gas exchange function and the inflammatory response in the septic acute lung injury.

Key words: C-phycocyanin, sepsis, acute lung injury, heme oxygenase-1

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