氟伐他汀对哮喘大鼠气道重建的影响及其机制  

Effect of fluvastatin on airway remo-deling in asthmatic rats and its mechanism

作　　者：王立[1] 吴昌归[1] 倪殿涛[1] 陈宏谦[1] 

机构地区：[1]第四军医大学西京医院呼吸内科,陕西西安710033

出　　处：《第四军医大学学报》2007年第7期637-640,共4页Journal of the Fourth Military Medical University

摘　　要：目的:观察羟甲基戊二酰辅酶A(HMG-CoA)还原酶抑制剂氟伐他汀对大鼠哮喘模型气道重建的影响.方法:将50只SD雄性大鼠随机分为5组:空白对照组(A组),哮喘组(B组),地塞米松组(C组),氟伐他汀组(D组)及氟伐他汀与地塞米松合用组(E组).以10g/L卵白蛋白(OVA)腹腔注射致敏并长期吸入激发制备慢性哮喘模型.用免疫组织化学方法检测各组大鼠肺组织中增殖细胞核抗原(PCNA),P21ras和Ⅲ型胶原的表达,采用图像分析方法测量气道壁内周长(Pi)及平滑肌面积(WAm).结果:①氟伐他汀对气道重建具有抑制作用:D组的WAm/Pi(4.44±0.95)μm2/μm,Ⅲ型胶原和PCNA表达(32±6,38±10)均低于B组[(7.01±1.54)μm2/μm,55±8,68±12](P均<0.05);②D组对气道重建的抑制作用弱于C组和E组:D组的WAm/Pi,Ⅲ型胶原和PCNA表达均高于C组[(3.14±1.06)μm2/μm,21±6,26±6]和E组[(3.03±0.87)μm2/μm,20±7,25±7](P均<0.05);③D组P21ras表达的吸光度值(24±11)明显低于B组(57±10)(P<0.05).P21ras表达与PCNA(rs=0.685,P<0.05)和Ⅲ型胶原(rs=0.530,P<0.05)的表达分别呈正相关.结论:氟伐他汀可延缓哮喘气道重建的进程,这种作用与P21ras抑制相关,但其抑制增生的作用弱于地塞米松.AIM ： To investigate the effect of hydroxy-methylglutaryl-CoA （HMG-CoA） reductase inhibitor, fluvastatin, on airway remodeling in asthmatic rats. METHODS： The male Sprague-Dawly rats were randomly divided into 5 groups with 10 rats in each group： the normal control group （A）, the model group （B）, the dexamethasone treated group （C）, the fluvastatin treated group （ D）, and the dexamethasone and fluvastatin treated group （E）. The asthmatic rat model was established by intraperitoneal injection and repeated inhalation of 10 g/L ovalbumin. The changes of collagen type Ⅲ , proliferation cell nuclear antigen （PCNA） and P21ras contents in the airway wall were detected by immunohistecbemistry, and the internal perimeter of bronchi （Pi） and the area of bronchial smooth muscle （WArn） were measured by the computerized image analysis system. RESULTS： ①Fluvastatin inhibitated the proliferation in airway remodeling： The WAm/Pi [ （4.44 ±0.95） um^2/um], the contents of collagen type Ⅲ （32 ±6） and PCNA （38 ＋10） in group D were lower than those in group B [ （7.01 ± 1.54） um^2/um, 55 ± 8, 68 ± 12 ], the difference being significant （ all P 〈 0.05 ） ; ②Fluvastatin was less effective in inhibition on the course of airway remodeling than dexamethasone and dexamethasone and fluvastatin combination ： The WAm/Pi, the contents of collagen type Ⅲ and PCNA in group D were higher than those in group C [（3.14 ± 1.06） um^2/um, 21 ±6. 26 ±6] and group E [ （3.03 ± 0.87） um^2/um, 20 ± 7, 25 ± 7] respectively, the difference being significant （ all P 〈 0. 05 ）. ③The contents of P21ras in group D （24 ± 11 ） were lower, as compared with group B （57 ± 10, P 〈 0.05 ）. A close correlation was demonstrated between P21ras and PCNA （ rs = 0. 685, P 〈 0. 05 ）. The same positive correlation was found between P21ras and collagen type Ⅲ （ rs = 0. 530, P 〈 0.05 ）. CONCLUSION ： Fluvastatin could delay the course of airway remo

关 键 词：氟伐他汀 支气管哮喘 气道重建 癌基因蛋白质p21(ras) 

分 类 号：R562.25[医药卫生—呼吸系统]