阿托伐他汀对哮喘大鼠过氧化物酶体增殖因子活化受体γ的作用及气道重塑的影响  

Effect of atorvastatin on airway remodeling and peroxisome proliferator-activated receptor-gamma expression and its mechanism in asthmatic rats

作　　者：刘明伟[1] 苏美仙[2] 蔡绍曦[3] 李岚[1] 何杰明[1] 

机构地区：[1]云南省昆明市延安医院呼吸二科,昆明650051 [2]昆明医学院第二附属医院外科重症监护室,昆明650101 [3]南方医科大学附属南方医院呼吸科,广州510515

出　　处：《解剖学报》2011年第3期361-366,共6页Acta Anatomica Sinica

基　　金：云南省科学技术厅资助项目(2010C093)

摘　　要：目的观察羟甲基戊二酰辅酶A(HMG-CoA)还原酶抑制剂阿托伐他汀对大鼠哮喘模型气道重建的影响。方法将80只SD雄性大鼠随机分为4组:空白对照组、哮喘组、地塞米松组、阿托伐他汀组。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过氧化物酶体增殖因子活化受体γ(PPAR-γ)、NF-κβ、Ⅲ型胶原的表达,同时图像分析方法测量气道壁内周长、平滑肌面积。结果 1.阿托伐他汀组的大鼠肺内嗜酸性粒细胞、淋巴细胞降低,肺组织中PPAR-γ表达增加,NF-κβ阳性细胞数降低与对照组比较差异具有统计学意义(P<0.05),与地塞米松组相比差异无统计学意义(P>0.05);PPAR-γ在肺内表达量与NF-κβ的活化细胞数呈负相关(rs=-0.530,P<0.05)。2.阿托伐他汀组支气管管壁面积(WAm)/Pi、平滑肌面积/Pi、N/Pi、Ⅲ型胶原的表达降低,与对照组比较差异具有统计学意义(P<0.05);与地塞米松组相比差异无统计学意义(P>0.05)。结论阿托伐他汀具有促进哮喘大鼠PPAR-γ的产生,抑制NF-κβ的活化,可延缓哮喘气道重建的进程,其抑制增生的作用与地塞米松类似。Objective To investigate the effect of hydroxy-methylglutaryl-CoA （HMG-CoA） reductase inhibitor, atorvastatin,on airway remodeling in asthmatic rats. Methods The male Sprague-Dawly rats were randomly divided into 4 groups with 20 rats in each group：the control group,the model group,the dexamethasone treated group and the atorvastatin treatment group. The asthmatic rat model was established by intraperitoneal injection and repented inhalation of 10g/L ovalbumin. The changes of collagen type Ⅲ , peroxisome proliferator-activated receptor-gamma （ PPAR-γ ） , the nurmber of nuclear factor-kβ positive cells, inflammatory ceils in the airway wall, were detected by immunohistochemical and pathological methods;the internal perimeter of bronchi（Pi） , the area of bronchial smooth muscle（WArn） and bronchus wall were measured by the computerized image analysis system. Results 1. The numbers of eosinophils, lymphocytes, nuclear factor-kβ positive cells,the contents of collagen type m were lower and the expression of PPAR-γ was higher in atorvastatin group than that of the model group, the difference being significant （ all P 〈 0. 05 ） ; compared with dexamethasone no statistically significant（P 〉 0.05） ; The WAm/Pi, bronchu smooth muscle area/Pi, N/Pi in atorvastatin group were lower than that of the model group, the difference was significant （ all P 〈 0. 05 ）. The negative correlation was found betweenexpression of PPAR-γ and the nurmber of nuclear factor-kβ positive cell （ rs = - 0. 530, P 〈 0.05 ）. ConclusionAtorvastatin can promote the expression of PPAR-γ, mRNA level, inhibit expression of nuclear factor-kβ and inflammatory cells infiltration in the airway wall, delay airway wall remodeling in asthmatic rats, but effect of atorvastatin on airway remodeling is no less effective than the inhibition of dexamethasone.

关 键 词：阿托伐他汀 过氧化物酶增殖体激活受体Γ 支气管重塑 免疫组织化学 大鼠 

分 类 号：R562[医药卫生—呼吸系统]