藻蓝素对脓毒性急性肺损伤大鼠血红素氧合酶-1表达的影响及分子机制

Effect of C-phycocyanin on Heme Oxygenase-1 Expression and its Molecular Mechanism in Acute Lung Injury Septic Rats

目的观察藻蓝素(CPC)对脓毒症急性肺损伤(ALI)大鼠血红素氧合酶-1(HO-1)表达的影响及分子机制。方法 SD大鼠根据不同实验目的随机分为对照组、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给予浓度为20、40、60 mg/kg CPC腹腔注射。术后72 h后获肺组织标本,观察CPC处理前后HO-1蛋白的表达,比色法检测HO-1酶活性改变情况。提取组织总蛋白和核蛋白,Western blot检测蛋白激酶B(Akt)磷酸化以及转录因子E2相关因子2(Nrf2)核转位情况。化学发光法检测超氧化物的含量。结果 CPC处理可明显促进ALI的肺组织中HO-1的表达,并能增强其酶活性。同时,CPC也可促进Akt磷酸化,并能诱导转录因子Nrf2核转位。同时,CPC也可显著减少大鼠肺组织中过氧化物产生,而HO-1抑制剂锡原卟啉Ⅸ(SnPP)能明显降低CPC对超氧化物的抑制作用。结论 CPC诱导HO-1表达可能与Akt磷酸化以及Nrf2的激活有关。

Objective To observe the effect of C-phycocyanin （ CPC ） on Heme oxygenase-1 （ HO-1 ） expression and its molecular mechanism in acute lung injury （ ALI） in septic rats. Methods SD rats were randomly divided into control group,model group and CPC group. Cecal ligation and puncture was used to establish 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 per-itoneal injection. 72h after the operation,serum and lung tissue were obtained,and expression of HO-1 and its enzymic activ-ity were detected by Western blot and colorimetric method,respectively. The total proteins in lung tissue and the nuclear proteins were extracted,phosphorylation of Akt and nuclear translocation of Nrf2 were detected by Superoxide Level produc-tion in Lungs and were measured by chemiluminescence. Results CPC could significantly induce ALI rats expression of HO-1,and increase its enzymic activily. In addition,CPC could also induce Akt phosphorylation and Nrf2 nuclear transloca-tion. Furthermore, CPC could elevate superoxide formation. However, blocking HO-1 activity by tin protoporphyrin IX （ SnPP） ,an HO-1 inhibitor,markedly abolished the inhibitory effect of superoxide production induced by CPC in septic-in-duced ALI rats. Conclusion CPC induced HO-1 expression in septic-induced ALI rats is mediated by Akt and Nrf2.