Lung histopathological and ultrastructural changes in rats with bleomy-cin-induced pulmonary fibrosis / 中国病理生理杂志

ABSTRACT

AIM:This study aims to investigate the histopathological and ultrastructural alterations in the lung tissues of rats induced by a single intratracheal administration of bleomycin,with the objective of establishing a reliable model for future applications.METHODS:Six to eight-week-old SD rats were randomly allocated into two groupsthe control group and the model group(n=12).Pulmonary fibrosis was induced in the rat models by a single intratracheal in-stillation of bleomycin(3 mg/kg),while an equivalent volume of saline was administered to the control group.The rats were executed on the 42nd day.Twelve rats remained in the control group,while nine rats remained in the model group.Lung tissue imaging was conducted using CT scans.Lung function tests were performed to assess changes in forced vital capacity(FVC)and dynamic lung compliance(Cdyn).Lung stiffness was determined through Young's modulus testing using a rheometer.The pathological structure of lung tissues was examined using both HE and Masson staining methods.Additionally,transmission electron microscopy was employed to evaluate collagen deposition in lung tissues,alveolar type Ⅱ epithelial cells,macrophages,and ultrastructural changes of the respiratory membrane.RESULTS:CT scans revealed honeycomb patterns in the lungs of model rats,along with partial bronchiectasis/bronchiectasis.In comparison to the con-trol group,the model group exhibited significantly lower FVC and Cdyn values,while lung stiffness were increased.HE and Masson staining demonstrated that rats in the model group exhibited alveolar structure destruction,alveolar septum thickening,inflammatory cell infiltration,and collagen deposition in alveolar septum.Transmission electron microscopy revealed several abnormalities in the model groupincreased collagen fibers in the alveolar septa,misalignment of micro-villi in alveolar type Ⅱ epithelial cells,wrinkled nuclei with increased heterochromatin,swollen cytoplasmic mitochon-dria,fractured or haphazardly structured mitochondrion cristaes,and a significant decrease in their number(P＜0.05).Furthermore,lamellar bodies were vacuolated and reduced in number(P＜0.05),and dilated endoplasmic reticulums with degranulation were observed.There was an increase in alveolar macrophages and interstitial macrophages(P＜0.01).The respiratory membrane displayed structural disruptions and an increase in thickness(P＜0.01).CONCLUSION:Bleomycin induces decreased lung compliance,alveolar epithelial injury,alveolar septum thickening,collagen deposi-tion,and an increase in interstitial macrophages,ultimately resulting in pulmonary fibrosis in rats.