International Research in Chinese Medicine

Objective To study the effects of Wuyiyinqiao Jianguo Prescription on lung mucosal immunity and related cytokines in mice with LPS induced chronic lung injury. Methods A mouse model of chronic lung injury was established by repeated infusion of LPS (30μg/6μL) from nasal cavity to respiratory tract (day 1, day 29 and day 57). The mice were randomly divided into control group, model group, low (5.0g crude drug /kg), medium (10.0g crude drug /kg) and high (20.0g crude drug /kg) dose groups. After successful modeling, the animals were anesthetized and killed after 3 weeks after receiving the test material, and the lung tissue and pulmonary mucosal tissue were extracted. HE staining was used to observe the pathological changes of lung tissue. The levels of IL-4, IL-6, TGF-β, IFN-γ and TNF-α in lung mucosa were determined by ELISA. The expression of IgA and pIgR proteins and the distribution and intensity of Ang II, ACE and ACE2 proteins in lung mucosa were detected by Western blot and immunohistochemistry, respectively. Results Compared with the control group, the pulmonary alveolar atrophy, septum widening, hyperemia and edema, and a large number of inflammatory infiltrates were observed in the model group, and the histopathological injury score was significantly increased (P < 0.05). The expressions of IgA and pIgR proteins in lung mucosal tissues of mice in model group were significantly increased (P < 0.05), and the levels of IgA related cytokines IL-4, IL-6, TGF-β and PIGr-related cytokines IFN-γ and TNF-α were significantly higher than those in control group (P < 0.05). The mean optical density intensity (IOD/area) of Ang II, ACE and ACE2 protein staining distribution in lung mucosal tissue of mice in model group was significantly higher than that in control group (P < 0.05). Compared with model group, Wuyiyinqiao Jiangjian formula reduced the damage degree of lung tissue in mice with lung injury in a dose-dependent manner (P < 0.05), and inhibited the decreased expression of IgA and pIgR protein and the increased levels of IL-6 and IFN-γ in lung mucosal tissue of mice with lung injury significantly in each dose group (P < 0.05). The elevated levels of IL-4, TGF-β and TNF-α in lung mucosal tissue of mice with lung injury were significantly inhibited by the high dose of WuyiYinjujian prescription (P < 0.05). In addition, it was found that Wuyiyinqiao Jianguo prescription inhibited the enhancement of Ang II, ACE and ACE2 protein staining distribution and the increase of average optical density intensity in lung mucosal tissues of mice with lung injury in a dose-dependent way. Compared with model group, there were significant differences between medium and high dose groups (P < 0.05). Conclusion By regulating the expression of IgA and pIgR, as well as the levels of IL-4, IL-6, TGF-β, IFN-γ and TNF-α, WuyiYinjujian prescription can inhibit the overexpression of Ang II, ACE and ACE2 activity in lung mucosa. In this way, the lung mucosal immune function can be regulated to improve the degree of lung mucosal injury induced by LPS.

Wuyi Yinqiao Fangyi prescription; Lung mucosal injury; Respiratory mucosal immunity; Mice; lipopolysaccharide