CAJ | 학술논문

目的：探讨博来霉素性肺纤维化大鼠 NADPH 氧化酶介导的细胞外基质重构机制。方法40只 SD 大鼠随机分为4组：对照组、模型组、乙酰香草素低剂量和高剂量组。一次性气管注入博来霉素复制大鼠肺纤维化模型，乙酰香草低剂量组灌胃乙酰香草素1μmol/ L，高剂量组灌胃乙酰香草素10μmol/ L 治疗，对照组大鼠给予等剂量的生理盐水。分析各组大鼠肺组织羟脯氨酸及丙二醛（MDA）及超氧化物歧化酶（SOD）含量，Western Blotting 法分析各组大鼠肺组织 NADPH 氧化酶亚基及细胞外基质重构相关酶系的表达。结果模型组大鼠肺组织羟脯氨酸及 MDA 水平明显增高，SOD 水平明显降低；模型组大鼠肺组织 NADPH 氧化酶亚基 p22phox 及 p47phox 表达明显增强，且 MMP2/9及TIMP1/2的表达也明显增强。低剂量和高剂量的乙酰香草素均可以明显改善上述指标的异常（ P ﹤0.05，P ﹤0.01），且具有剂量依从性效果。结论乙酰香草素通过抑制 NADPH 氧化酶的过度激活及细胞外基质重构改善博来霉素性肺纤维化损伤。
목적：탐토박래매소성폐섬유화대서 NADPH 양화매개도적세포외기질중구궤제。방법40지 SD 대서수궤분위4조：대조조、모형조、을선향초소저제량화고제량조。일차성기관주입박래매소복제대서폐섬유화모형，을선향초저제량조관위을선향초소1μmol/ L，고제량조관위을선향초소10μmol/ L 치료，대조조대서급여등제량적생리염수。분석각조대서폐조직간포안산급병이철（MDA）급초양화물기화매（SOD）함량，Western Blotting 법분석각조대서폐조직 NADPH 양화매아기급세포외기질중구상관매계적표체。결과모형조대서폐조직간포안산급 MDA 수평명현증고，SOD 수평명현강저；모형조대서폐조직 NADPH 양화매아기 p22phox 급 p47phox 표체명현증강，차 MMP2/9급TIMP1/2적표체야명현증강。저제량화고제량적을선향초소균가이명현개선상술지표적이상（ P ﹤0.05，P ﹤0.01），차구유제량의종성효과。결론을선향초소통과억제 NADPH 양화매적과도격활급세포외기질중구개선박래매소성폐섬유화손상。
Objective We aimed to prove the hypothesis that NADPH oxidase mediated extracellular matrix remodeling plays an important role in bleomycin induced pulmonary fibrosis. Methods SD rats were divided into 4 groups:control group,model group and apocynin low dose group and high dose group. Pulmonary fibrosis rats were duplicated by single trachea injection of bleomycin and drugs were administrated by oral. The content of hydroxyproline,MDA and SOD were assayed. The expression of NADPH oxidase subunits and extracellular remodeling enzymes were detected by Western blotting. Results MDA and hydroxyproline concentration was increased while SOD content was decreased in bleomycin group. The expression of MMP2 / 9,TIMP/ 2 and p22phox as well as p47phox was increased greatly. Apocynin medication alleviated those abnor-malities greatly in a dose dependent manner. Conclusion Apocynin improves bleomycin induced pulmonary fibrosis by inhibiting NADPH oxidase and extracellular matrix remodeling.