CAJ | 학술논문

目的：探讨辛伐他汀对老年COPD大鼠肺泡上皮细胞凋亡干预作用。方法39只老年Wistar大鼠随机分为正常组（A组）、COPD模型组（B组）及辛伐他汀干预组（C组），每组各13只。B、C组采用熏香烟联合气道内滴入脂多糖法建立大鼠COPD模型，在造模2周后C组给予辛伐他汀（2.5 mg/kg）灌胃6周，A、B组给予同等量生理盐水灌胃。8周后处死大鼠，并观察大鼠肺组织病理变化，检测肺泡上皮细胞凋亡及凋亡相关因子半胱氨酸蛋白酶-3（Caspase-3）、诱导型一氧化氮合酶（iNOS）、内皮型一氧化氮合酶（eNOS） mRNA表达，并计算凋亡指数。结果与A组相比， B组和C组凋亡指数、Caspase-3及iNOS mRNA表达增加（P均＜0.01），eNOS mRNA表达降低（P＜0.01）；与B组相比，C组凋亡指数、Caspase-3及iNOS mRNA表达降低（P均＜0.01），eNOS mRNA表达增加（P＜0.01）。各组间肺泡上皮细胞凋亡指数与Caspase-3及iNOS mRNA表达呈正相关（P＜0.05），与eNOS mRNA表达呈负相关（P＜0.05）。各组间Caspase-3 mRNA与iNOS mRNA表达呈正相关（P＜0.05），与eNOS mRNA表达呈负相关（P＜0.01）。结论辛伐他汀通过增加肺组织eNOS基因表达，抑制iNOS及Caspase-3基因表达，抑制了老年COPD大鼠肺泡上皮细胞凋亡。
목적：탐토신벌타정대노년COPD대서폐포상피세포조망간예작용。방법39지노년Wistar대서수궤분위정상조（A조）、COPD모형조（B조）급신벌타정간예조（C조），매조각13지。B、C조채용훈향연연합기도내적입지다당법건립대서COPD모형，재조모2주후C조급여신벌타정（2.5 mg/kg）관위6주，A、B조급여동등량생리염수관위。8주후처사대서，병관찰대서폐조직병리변화，검측폐포상피세포조망급조망상관인자반광안산단백매-3（Caspase-3）、유도형일양화담합매（iNOS）、내피형일양화담합매（eNOS） mRNA표체，병계산조망지수。결과여A조상비， B조화C조조망지수、Caspase-3급iNOS mRNA표체증가（P균＜0.01），eNOS mRNA표체강저（P＜0.01）；여B조상비，C조조망지수、Caspase-3급iNOS mRNA표체강저（P균＜0.01），eNOS mRNA표체증가（P＜0.01）。각조간폐포상피세포조망지수여Caspase-3급iNOS mRNA표체정정상관（P＜0.05），여eNOS mRNA표체정부상관（P＜0.05）。각조간Caspase-3 mRNA여iNOS mRNA표체정정상관（P＜0.05），여eNOS mRNA표체정부상관（P＜0.01）。결론신벌타정통과증가폐조직eNOS기인표체，억제iNOS급Caspase-3기인표체，억제료노년COPD대서폐포상피세포조망。
Objective To explore the effect of simvastatin on the apoptosis of alveolar epithelial cells in aged chronic obstructive pulmonary disease (COPD)model rat lungs. Methods Thirty-nine aged wistar rats were randomly divided into three groups:the normal group (group A,n=1 3 ),the COPD model group (group B,n=1 3)and the simvastatin treatment group (group C,n=1 3). The COPD rat model was estab-lished by cigarette smoke combined with lipopolysaccharide. Simvastatin,at a dose of (2.5 mg/kg),was ad-ministered orally to rats in group C once per day for 6 weeks. Meanwhile,Group A and B received equivalent normal saline. At the end of the 8 weeks,rats were sacrificed after the simvastatin therapy. Thereafter,the pathological changes of lung tissue were observed,and the alveolar epithelial cell apoptosis was detected. The apoptosis related factors Caspase-3,endothelial nitric oxide synthase (eNOS)and inducible nitric oxide syn-thase (iNOS)were determined. In addition,the apoptosis index (AI)was calculated. Results In group B and C,the AI and expression of Caspase-3 and iNOS mRNA increased significantly (P<0.01 ),whereas the expression of eNOS mRNA decreased (P<0.01 )compared with group A. In group C,the AI and expression of Caspase-3 and iNOS mRNA decreased significantly (P<0.01 ),and the expression of eNOS mRNA in-creased (P<0.01 )compared with group B. In addition,The AI was positively correlated with Caspase-3 and iNOS expression,(P<0.05 )and negatively correlated with eNOS mRNA (P<0.05 ). Caspase-3 mRNA ex-pression was identified to be positively correlated with iNOS mRNA expression (P<0.05 ),and negatively cor-related with eNOS mRNA (P<0.01 )expression in all groups. Conclusion Simvastatin could attenuate the alveolar epithelial cells apoptosis in aged COPD rat lungs and this mechanism may be associated with the up-regulated expression of eNOS mRNA and down-regulated expression of iNOS and Caspase-3 in lung tissues.