HO-1在CCK-8减轻脂多糖所致的急性肺损伤中的作用

目的： 探讨血红素氧合酶（HO）-1在八肽胆囊收缩素（CCK-8）减轻脂多糖（LPS）所致急性肺损伤（ALI）中的作用。方法: 将大鼠随机分为5组：正常对照组、LPS组、CCK-8+LPS组、LPS+Hm（氯血红素，CO供体）组、LPS+ZnPP（锌原卟啉，HO-1特异性阻断剂）组。各组给药后2 h、6 h、12 h行支气管肺泡灌洗、检测支气管肺泡灌洗液（BALF）中中性粒细胞（PMN）数目；进行肺组织的形态学观察；测定肺组织中丙二醛（MDA）含量和HO-1蛋白活性；应用RT-PCR和Western blotting技术检测给药后6h肺组织中HO-1 mRNA和蛋白的表达情况。结果: LPS组肺组织出现损伤性变化，同时BALF中PMN数目、肺组织中MDA含量、HO-1蛋白活性、HO-1 mRNA和蛋白的表达均高于相应对照组（均P<0.05）；CCK-8+LPS和LPS+Hm组肺组织损伤程度、BALF中PMN数目和肺组织中MDA含量低于相应LPS组，而肺组织中HO-1蛋白活性、HO-1 mRNA和蛋白的表达均高于相应LPS组（均P<0.05）；LPS+ZnPP组肺组织损伤程度、BALF中PMN数目和肺组织中MDA含量分别高于相应LPS组，而肺组织中HO-1蛋白活性、HO-1 mRNA和蛋白的表达分别低于相应LPS组（均P<0.05）。结论: CCK-8可部分通过HO-1介导的抗氧化、抑制PMN聚集等效应来发挥减轻LPS所致的肺损伤作用。

Role of heme oxygenase in cholecystokinin octopeptide ameliorating acute lung injury induced by lipopolysaccharide

AIM:To study the role of heme oxygenase (HO)-1 in the mechanism of cholecystokinin-octapeptide (CCK-8) for attenuation of acute lung injury (ALI) induced by lipopolysaccharide (LPS). METHODS: Adult male rats were randomly divided into five groups: control group, LPS group, CCK-8 LPS group, LPS Hm (hemin, HO-1 donor) group and LPS ZnPP (zinc protoporphyrin, specific inhibitor of HO-1) group. PMN number in bronchoalveolar lavage fluid (BALF), the structure of the lung, MDA content, HO-1 activity, the expressions of HO-1 mRNA and protein in the lung were detected respectively. RESULTS: The lung injury in LPS group was observed, at the same time the numbers of PMN, the content of MDA, the activity and the expression of HO-1 were all higher than those in control group (all P<0.05). The degree of lung injury, PMN numbers and MDA content were lower, while the activity and the expression of HO-1 in CCK-8 LPS and LPS Hm group were higher than those in LPS group (all P<0.05). However, the degree of lung injury, PMN numbers and MDA content were higher, the activity and the expression of HO-1 were lower in LPS ZnPP than those in LPS group respectively (all P<0.05). CONCLUSION: CCK-8 attenuates the LPS-induced ALI by means of anti-oxidation and inhibits PMN aggregation, which are both mediated by HO-1 partly.