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 wall were measured. Expression and localization of transforming growth factor beta(1) (TGF-beta(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) x 10(5)/ml], absolute neutrophil count in BALF from S group [(17.1 +/- 10.8) x 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-beta(1) in the lung of S group was significantly higher than that in A group. (3) The levels of HA [(152.5 +/- 36.3) micro g/ml] and PCIII [(40 +/- 8) micro g/ml] in serum and the levels of HA [(94 +/- 35) micro g/ml] and PCIII [(39 +/- 7) micro g/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) x 10(5)/ml, 187 +/- 61, (6.0 +/- 2.3)%, (9.69 +/- 5.61) micro g/ml, (63.0 +/- 11.6) micro g/ml, (16 +/- 6) micro g/ml, (52 +/- 12) micro g/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.