[Animal modeling] - quantitative oral and nasal inhalation method to establish a rat model of chronic obstructive pulmonary disease

  Objective: To compare the differences between the rat models of chronic obstructive pulmonary disease induced by inhalation of smoke through the mouth and nose, combined with lipopolysaccharide tracheal infusion, and systemic exposure to smoke combined with lipopolysaccharide tracheal infusion, in order to provide a new modeling method for the construction of COPD models.

  Method: 90 male SD rats were randomly divided into a normal control group, a smoke exposure group, and a smoke inhalation group, with 30 rats in each group. The smoke whole body exposure group was exposed to smoke using a self-made smoke box, while the smoke oral and nasal inhalation group was exposed to smoke using a quantitative smoking device. Both groups of animals were exposed to smoke once a day, for 60 minutes each time, for 8 consecutive weeks. LPS (1 mg/kg) was injected through the trachea on the 1st, 7th, 15th, and 21st day of modeling, respectively, to induce the establishment of a COPD model. Quality control of smoke generated by quantitative smoking devices and self-made smoking boxes, including verification of concentration stability and uniformity of smoke particles, detection of particle size distribution of smoke particles, and pulmonary function examination, inflammatory cytokine interleukin-6 (IL-6) in bronchoalveolar lavage fluid, and tumor necrosis factor at 4, 6, and 8 weeks of modeling, respectively- α (TNF)- α) Compare the differences between the two modeling methods through content detection and histopathological examination.

  The quantitative smoking device can generate smoke with stable concentrations (concentrations of 1 1 mg/L (in particles) and 0 1 mg/L (based on nicotine), and its median mass aerodynamic diameter (MMAD) (based on nicotine) is 0 eighty-six μ m. The geometric standard deviation (GSD) is 2 12. The stability and uniformity deviation of smoke concentration generated by self-made smoking boxes are significantly greater than those of quantitative smoking devices; FEV0 of lung function in rats with smoke oral and nasal inhalation group 2/FVC and lung compliance (Cdyn) indicators showed a more significant decrease compared to the smoke exposed group, while airway resistance (penh) increased more significantly; IL-6 and TNF in alveolar lavage fluid of rats in the smoke oral and nasal inhalation group- α The level showed a significant increase after 6 weeks of modeling, while rats in the smoke exposed group needed to wait until 8 weeks of modeling. After modeling, the degree of bronchitis in rats in the smoke inhalation group and the whole body exposure group was basically the same, but the degree of emphysema in the oral inhalation group was more severe, and compared with the whole body exposure group (modeling for 8 weeks), the time when statistical differences in emphysema appeared in the oral inhalation group (modeling for 6 weeks) was earlier; The mean linear interval (MLI) of the smoke inhalation group significantly increased from 4 to 8 weeks of modeling, while the mean alveolar number (MAN) significantly decreased from 6 to 8 weeks of modeling; The whole body exposure group to smoke only