摘要
目的 观察慢性支气管炎 (简称慢支 )和肺气肿大鼠模型气道炎症及重塑的发病特点以及红霉素药物干预的影响。方法 将 4 3只雄性Wistar大鼠分 8组 ;正常对照组 (A组 ,5只 )、生理盐水对照组 (P组 ,5只 )、慢支组 (L组 ,6只 )、慢支 +肺气肿组 (S组 ,6只 )、低剂量红霉素治疗组 (E1组 ,5只 )、高剂量红霉素治疗组 (E2 组 ,6只 )、低剂量红霉素预防治疗组 (E10 组 ,5只 )、低剂量红霉素预防治疗组 (E2 0 组 ,5只 )。用气管内注入脂多糖 (LPS)及每天烟熏的混合刺激方法制作慢支与肺气肿动物模型 ,4周后收集支气管肺泡灌洗液 (BALF)进行细胞学计数和分类检查 ,对大鼠肺脏进行病理学检查 ,检测各组细小支气管平滑肌和胶原层厚度 ,并用免疫组化法观察转化生长因子 β1(TGF β1)在支气管肺内的表达 ,用放射免疫法检测血清和BALF中Ⅲ型前胶原 (PCⅢ )、透明质酸 (HA)的变化。结果 (1)S组BALF中中性粒细胞分类计数为 [(17 1± 10 8)× 10 5/ml],A组为 [(0 9± 0 7)×10 5/ml],两组比较差异有显著性 (P <0 0 1) ;(2 )病理积分 :S组为 (32 9± 114 )分 ,A组为 (6 7± 2 5 )分 ;S组细小支气管平滑肌及胶原层厚度为 (9 6± 2 6 ) % ,A组为 (6 1± 1 8) % ,两组比较差异有显著性(P分别为 <0 0 1、<0 0 5 ) ;
Objective To study the pathological features of airway inflammation and remodeling in rats with chronic bronchitis(CB) and emphysema and to evaluate the protective and therapeutic effects of erythromycin(EM). Methods Forty-three Wistar rats were assigned to eight groups: normal control group (A group, n=5), normal saline solution group(P group, n=5), CB group (L group, n=6), CB and emphysema group(S group, n=6), low-dose EM-treatment group(E 1 group, n=5), high-dose EM-treatment group(E 2 group, n=6), low-dose EM-prevention group(E 10 group, n=5) and high-dose EM-prevention group(E 20 group, n=5). The rat model of CB and emphysema was established by intratracheal instillation of lipopolysaccharide(LPS) and daily exposure to cigarette smog. After four weeks, total and differential cell counts in bronchoalveolar lavage fluid(BALF) were observed, and the pathomorphological changes in the lung were analyzed. The thickness of the smooth muscles and collagen in the bronchial wallwere measured. Expression and localization of transforming growth factor β 1 (TGF-β 1) were observed in the bronchi and lung tissues by immunohistochemistry. The levels of hyaluronic acid(HA) and procollagen type Ⅲ(PCⅢ) in the serum and BALF were determined by the radioimmunoassay(RIA). Results (1) Compared with A group [(0.9±0.7)×10 5/ml], absolute neutrophil count in BALF from S group [(17.1±10.8)×10 5/ml] were significantly higher ( P<0.01). (2) Both the pathologic scores obtained from the S group (329±114) and P group (67±25), and the thickness of smooth muscles and collagen from S group [(9.6±2.6)%] and A group [(6.1±1.8)%] were statistically different ( P<0.01, P<0.05, respectively) . Expression of TGF-β 1 in the lung of S group was significantly higher than that in A group. (3) The levels of HA [(152.5±36.3) μg/ml] and PCⅢ [(40±8) μg/ml]in serum and the levels of HA [(94±35) μg/ml] and PCⅢ [(39±7) μg/ml] in BALF in S group were higher than those in A group ( P<0.01). (4)After treatment with 100 mg/kg EM, absolute neutrophil count in BALF, the pathologic scores, the thickness of smooth muscles and collagen in the bronchi, the levels of PCⅢ and HA in serum and the levels of PCⅢ and HA in BALF were reduced to (2.1±1.4)×10 5/ml, 187±61, (6.0±2.3)%, (9.69±5.61) μg/ml?(63.0±11.6) μg/ml, (16±6) μg/ml, (52±12) μg/ml, respectively. Statistical analysis revealed that there were significant differences as compared to those of group S ( P<0.05).Conclusions Many inflammatory cells especially neutrophils and alveolar macrophages might play an important role in the airway inflammation of CB and emphysema. Thickening of smooth muscles and collagen in the bronchi and the excessive depositions of extracellular matrix(ECM) constitute the fundamental pathological characteristic of airway remodeling in CB and emphysema. EM may prevent airway inflammation and remodeling to some degree.
出处
《中华结核和呼吸杂志》
CAS
CSCD
北大核心
2003年第12期750-755,共6页
Chinese Journal of Tuberculosis and Respiratory Diseases
关键词
慢性支气管炎
肺气肿
大鼠
气道炎症
气道重塑
实验
Chronic bronchitis
Pulmonary emphysema
Airway inflammation
Airway remodeling
Erythromycin
