【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其分子机制。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60 mg/kg CPC。术后72 h后获取血液及肺组织标本,检测Pa O2/Fi O2、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Pa O2/Fi O2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,Pa O2/Fi O2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,同时能增加HO-1的酶活性以及上调其mRNA水平(P<0.05)。此外,HO-1激动剂锡原卟啉(Co PP)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(Zn PP)能进一步促进细胞因子产生(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。更多还原

【Abstract】 Objective To observe the protective effect and molecular mechanism of C-phycocyanin(CPC) on acute lung injury in septic rats. Methods The 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 60 mg/kg of CPC by peritoneal injection. 72 h after the operation,serum and lung tissue were obtained,the Pa O2/ Fi O2,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) were analyzed. Enzymic activity of hemeoxygenase(HO)-1 and its mRNA was detected by colorimetric method and RT-PCR respectively. Results Pa O2/Fi O2,content of MDA,activity of MPO,and thewet to dry weight ratio significantly increased in the model group,after CPC treatment,the level of Pa O2/ Fi O2 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 increased,HO-1 acivity and mRNA level also increased(P < 0. 05). CPC may decrease the cytokines level,and upregulate HO-1 acitvity and mRNA expression. In addition,HO-1 agonist Co PP may synergize CPC to production of TNF-α,IL-6 and IL-10 1β,but HO-1 antagonist Zn PP may futher increase the cytokines production. Conclusions CPC may induce HO-1 expression,and thus relieve gas exchange function and the inflammatory response in the septic acute lung injury.更多还原