CAJ | 학술논문

目的观察阿托伐他汀对博莱霉素所致大鼠肺纤维化的抑制作用及其机制,探讨防治肺纤维化的新途径. 方法取SPF级雄性SD大鼠30只,随机分为生理盐水对照组、博莱霉素模型组、阿托伐他汀治疗组,每组各10只.生理盐水对照组气管内注入生理盐水0.2ml,其他2组气管内注入博莱霉素5mg/kg建立肺纤维化模型,此后阿托伐他汀治疗组每天给予阿托伐他汀10mg/kg灌胃,生理盐水对照组和博莱霉素模型组给予等量生理盐水灌胃.于第7天和第28天3组均各处死5只,苏木精-伊红(HE)染色法及Masson染色病理学观察肺泡炎性改变及肺纤维化改变;酶联免疫吸附法(ELISA)检测肺组织羟脯氨酸和肿瘤坏死因子-α(TNF-α)水平;Western blot法检测肺组织Kruppel-样因子2(KLF2)的蛋白表达;采用实时聚合酶链反应(PCR)检测肺组织KLF2的mRNA表达. 结果博莱霉素模型组与生理盐水对照组比较病理学检查显示,大鼠肺组织在第7天出现出血渗出等炎性反应,第28天出现纤维化;而阿托伐他汀治疗组第7天肺组织的炎性反应及第28天纤维化程度都比博莱霉素模型组明显减轻.与生理盐水对照组比较,博莱霉素模型组肺组织羟脯氨酸和TNF-α水平明显升高(均P＜0.05),而KLF2蛋白含量和KLF2-mRNA的表达均明显降低(均P＜0.05);阿托伐他汀治疗组上述变化减轻,其肺组织的羟脯氨酸和TNF-α含量低于博莱霉素模型组(均P＜0.05),同时阿托伐他汀治疗组肺组织KLF2蛋白含量和KLF2-mRNA表达则高于博莱霉素模型组(均P＜0.05). 结论阿托伐他汀可减少炎性细胞分泌TNF-α、减轻博莱霉素导致的肺纤维化反应;其对于纤维化的抑制机制与上调KLF2-mRNA表达有关.
목적 관찰아탁벌타정대박래매소소치대서폐섬유화적억제작용급기궤제,탐토방치폐섬유화적신도경. 방법 취SPF급웅성SD대서30지,수궤분위생리염수대조조、박래매소모형조、아탁벌타정치료조,매조각10지.생리염수대조조기관내주입생리염수0.2ml,기타2조기관내주입박래매소5mg/kg건립폐섬유화모형,차후아탁벌타정치료조매천급여아탁벌타정10mg/kg관위,생리염수대조조화박래매소모형조급여등량생리염수관위.우제7천화제28천3조균각처사5지,소목정-이홍(HE)염색법급Masson염색병이학관찰폐포염성개변급폐섬유화개변;매련면역흡부법(ELISA)검측폐조직간포안산화종류배사인자-α(TNF-α)수평;Western blot법검측폐조직Kruppel-양인자2(KLF2)적단백표체;채용실시취합매련반응(PCR)검측폐조직KLF2적mRNA표체. 결과 박래매소모형조여생리염수대조조비교병이학검사현시,대서폐조직재제7천출현출혈삼출등염성반응,제28천출현섬유화;이아탁벌타정치료조제7천폐조직적염성반응급제28천섬유화정도도비박래매소모형조명현감경.여생리염수대조조비교,박래매소모형조폐조직간포안산화TNF-α수평명현승고(균P＜0.05),이KLF2단백함량화KLF2-mRNA적표체균명현강저(균P＜0.05);아탁벌타정치료조상술변화감경,기폐조직적간포안산화TNF-α함량저우박래매소모형조(균P＜0.05),동시아탁벌타정치료조폐조직KLF2단백함량화KLF2-mRNA표체칙고우박래매소모형조(균P＜0.05). 결론 아탁벌타정가감소염성세포분비TNF-α、감경박래매소도치적폐섬유화반응;기대우섬유화적억제궤제여상조KLF2-mRNA표체유관.
Objective To observe the inhibitory effect of atorvastatin on bleomycin-induced pulmonary fibrosis in SD rats and study their possible mechanism.Methods 30 male SD mice under SPF condition with average body weight of 250g were randomly allocated to three groups (n =10,each) of saline control group (control group),bleomycin-induced pulmonary fibrosis group (pulmonary fibrosis group) and atorvastatin treatment group (treatment group).Bleomycin (5mg/kg) (versus 0.2 ml saline in control group) were endotracheally instilled in pulmonary fibrosis group and the treatment group in order to establish the model of pulmonary fibrosis.Subsequently,the rats in the treatment group received daily atorvastatin (10 mg/kg) orally.5 rats in each group were sacrificed on 7th and 28th day after intratracheal instillation.Their lung tissues were taken and tested.The histological changes in the lungs were evaluated by hematoxylin-eosin and masson stain.The tumor necrosis factor (TNF-α) level and hydroxyproline content in lung tissues were measured by enzymelinked immunosorbent assay (ELISA).The expressions of Kruppel-like factor 2 (KLF2) protein and mRNA in lung tissues were measured by Western blotting and Real-Time PCR.Results The lung tissue in model group had significant bleeding and oozing inflammatory response on the 7th day and pulmonary fibrosis on the 28th day.Bleeding and oozing inflammatory response and pulmonary fibrosis were subdued in treatment group on the same days as compared to the model group.Hydroxyproline and TNF-α contents in lung tissue were significantly higher in model group than in control group (both P＜0.05).KLF2 protein and KLF2-mRNA expressions in lung tissues were significantly lower in model group than in control group (both P＜0.05).The above changes were partially reversed in treatment group.Compared to model group,treatment group showed that hydroxyproline and TNF-α contents in lung tissues were significantly reduced (both P＜0.05) and KLF2 protein and KLF2 mRNA expressions in lung tissues were significantly increased (both P＜ 0.05).Conclusions Atorvastatin can reduce the secretion of TNF-α and alleviate bleomycin-induced pulmonary fibrosis.The mechanism inhibiting fibrosis might be associated with up-regulation of KLF2-mRNA expression.