[Establishment of a novel mouse mode of elastase-induced chronic obstructive pulmonary disease related osteoporosis]

To establish and evaluate the model of chronic obstructive pulmonary disease (COPD) with osteoporosis induced by elastase in mice.

Twenty four healthy female 8-week-old C57BL / 6 mice (weighing about 18 g) were randomly divided into three groups. The control group was given intratracheal drip of normal saline, the experimental group 1 and the experimental group 2 were given intratracheal drip of elastase, the control group and the experimental group 1 were kept for 8 weeks and then killed, the experimental group 2 was kept for 12 weeks and then killed. HE staining was used to evaluate the histopathological changes of lung and tibia in the control and experimental groups. The levels of serum inflammatory factors and broncho alveolar lavage factors (BALF) were detected by ELISA. Micro CT was used to detect the bone mass related parameters of mouse femur. The expression of osteoclastic and osteogenic genes was detected by real-time fluorescence quantitative PCR.

Lung histopathology showed that the structure of alveoli in the experimental group was disordered, the walls of alveoli became thin or broken, and the alveoli cavity expanded. IL-6 and TNF-α in BALF were significantly higher than those in control group (P<0.001), while IL-1β and TNF-α in serum inflammatory factors were significantly higher than those in control group (P<0.001). BV / TV(bone volume fraction), TB.Th(average bone trabecular thickness) and TB.N(average bone trabecular number) in the experimental group were significantly lower than those in the control group (P<0.05), TB.Sp (average bone trabecular separation) and BS / BV (bone surface area fraction) in the experimental group were significantly higher than those in the control group (P<0.01). Compared with the control group, the expression of osteoclast related marker genes increased in the experimental group (P<0.05), but decreased in the experimental group(P<0.05). The results of experiment 1 and experiment 2 were time-dependent.

In this study, elastase was used to construct a COPD model with osteoporosis successfully, which provides a suitable animal model for the future study of the pathogenesis of COPD with osteoporosis.