Establishment and Evaluation of Rat Model for Chronic Obstructive Pulmonary Disease with Lung-spleen Qi Deficiency / 中国实验方剂学杂志

ABSTRACT

ObjectiveTo establish and evaluate a chronic obstructive pulmonary disease （COPD） model with lung-spleen qi deficiency. MethodA rat model mimicking COPD with lung-spleen qi deficiency was established by the combination of cigarette smoking and intratracheal instillation of lipopolysaccharide （LPS） along with gavage of Sennae Folium infusion. Forty male SPF-grade SD rats were randomly assigned to blank， model， and low- （L-FXY）， medium- （M-FXY）， and high-dose （H-FXY） Sennae Folium infusion groups. Other groups except the blank group were exposed to daily cigarette smoke， with LPS administrated via intratracheal instillation on the 1st and 14th days. On the 28th day of modeling， the L-FXY， M-FXY， and H-FXY groups were administrated with Sennae Folium infusion at 5， 10， and 20 g·kg-1， respectively， and at 4 ℃ for three weeks. The modeling lasted for 49 days. The general conditions （body mass， food intake， fecal water content， and anal temperature） and behaviors （grip strength test and tail suspension test） of rats in different groups were examined. The lung function， lung histopathology， D-xylose， amylase， and gastrin levels in the serum， interleukin（IL）-1β and IL-6 levels in the alveolar lavage fluid， levels of T-lymphocyte subsets （CD4+， CD8+， and CD4+/CD8+） in the peripheral blood， and thymus and spleen indices were measured. ResultTwo rats died in the H-FXY group. Compared with the blank group， both the M-FXY and H-FXY groups exhibited reduced body mass and food intake （P<0.01） and increased fecal water content （P<0.01）. The anal temperature in the H-FXY group was lower than that in the blank group （P<0.01）. The grip strength decreased in the modeling groups compared with the blank group （P<0.01）， and the duration of immobility in the tail suspension test increased in the M-FXY and H-FXY groups （P<0.05， P<0.01）. Compared with the blank group， the modeling groups showed reduced 0.3 second forced expiratory volume （FEV0.3）， FEV0.3/forced vital capacity （FVC）（P<0.01）， thickening of bronchial walls， proliferation of goblet cells， and the presence of emphysematous changes. In terms of gastrointestinal function， the M-FXY and H-FXY groups had lower levels of D-xylose， gastrin， and α-amylase than the blank group （P<0.01）. Regarding the immune and inflammatory indices， the M-FXY and H-FXY groups showed lower thymus and spleen indices than the blank group （P<0.01）. Compared with the blank group， the modeling groups presented lowered CD4+ level （P<0.01） and CD4+/CD8+ ratio （P<0.05， P<0.01） in the peripheral blood and elevated levels of IL-1β and IL-6 in the alveolar lavage fluid （P<0.01） than the blank group. ConclusionA model of COPD with lung-spleen Qi deficiency was established through the combination of daily cigarette smoke， intratracheal instillation with LPS， and gavage of Sennae Folium infusion. The comprehensive evaluation results suggested medium-dose （10 g·kg-1） Sennae Folium infusion for gavage during the modeling of COPD with lung-spleen Qi deficiency.