An Experimental Study On The Ultrastructure Changes Of Pulmonary Vessels And The Role Of Erythromycin In A Rat Model Of Chronic Bronchitis And Emphysema

Objective: (1) To study the ultrastructural changes and their role in the remodeling of intra-acinar pulmonary muscular arteries in rats with chronic bronchitis (CB) and emphysema. (2) To evaluate the protective and therapeutic effects of erythromycin (EM). Methods: 18 healthy male Wistar rats were divided into 3 groups randomly: normal control group (group A, n=6), CB and emphysema group (group B, n=6), EM-treatment group (group C, n=6). The rat model of CB and emphysema was established by intratracheal instillation of lipopolysaccharide (LPS) and daily exposure to cigarette smog. After eight weeks, artery blood gas analysis was observed, the ultrastructure changes of endothelial cells, smooth muscle cells and vascrlar wall of intra-acinar pulmonary muscular arteries were studied by transmission electron microscope; pathomorphological changes of the lung and the morphometric characteristics of intra-acinar pulmonary muscule arteries were analyzed, the immunohistochemical expression of eNOS in endothelial cells of intra-acinar pulmonary muscular arteries was analyzed with local and Semiquantitative analysis. Results: (1) Ultrastructural changes of intra-acinar pulmonary muscular arteries: compared with group A, ultrastructrural observation of intra-acinar pulmonary arteries of group B showed swelling and degeneration even necrosis of endothelial cells, the presence of abundant bubbles as wells as the diminished number of mitochondria in cytoplasm, degeneration of nuclei, the absence of intercellular junctions between the endothelial cells, irregularity and break of internal elastic laminar, proliferation and hyperplasia of synthetic phenotype smooth muscle cells with lesser microfilamens and dense bodies and dense patches but more other organelles. post-treatment, these changes of group C were improved significantly. (2) The morphometric characteristics of intra-acinar pulmonary muscular arteries: compared with group A and group C, the thickness of intimal layer of intra-acinar pulmonary muscular arteries of group B was significantly higher, the area of its lumen was lower, and the proportion of its muscular arteries was higher (p<0.01,each). (3) The immunohistochemical expression of eNOS in endothelial cells of intra-acinar pulmonary muscular arteries: compared with group A and group C, semiquantitative analysis of the immunohistochemical data revealed that the proportion of endothelial cells of intra-acinar pulmonary muscular arteries of group B showing positive immunoreaction to eNOS was lower (p<0.05,each). post-treatment, the proportion of endothelial cells showing positive immunoreaction to eNOS of group C was significant higher. The intensity expression of eNOS in endothelial cells of intra-acinar pulmonary muscular arteries was inversely related to the thickness of their intimal layer (r=-0.776,p<0.01) and was significant related to the area of their lumen (r=0.749,p<0.01). Conclusions: (1) The characteristics of the ultrastructural changes of intra-acinar pulmonary muscular arteries in rats with CB and emphysema are degeneration even necrosis of endothelial cells, proliferation of smooth muscle cells and extracellular matrix (ECM) under the endothelium, irregularity and break of internal elastic lamina and the presence of synthetic phenotype smooth muscle cells. (2) The damage of pulmonary vascular endothelial cells is the important pathologic basis of earlier period pulmonary vascular structural remodeling in rat with CB and emphysema. (4) EM may prevent the damage of pulmonary vascular endothelial cells and pulmonary vascular structural remodeling in rats with CB and emphysema to some degree.