目的 Mucins have long been regarded as exerting a role as a barrier to prevent mucosal infection but some data supporting overexpressed mucins induced airways obstruction and inflammation.We wonder if increased MUC5AC secretion provided benefit against murine gammaherpesvirus 68 (MHV-68) and MHV-68 induced pulmonary fibrosis.Firstly, we develop a combined pulmonary fibrosis and emphysema (CPFE) murine model by tracheal instillation of MHV-68 in long time cigarette smokeinduced old male emphysema mice.Then, an MUC5AC-overexpressing mouse model will be generated to understand whether increased MUC5AC secretion add protection against MHV-68 in CPFE murine model or induce airways obstruction and inflammation.方法 Firstly, Experimental mice were randomly divided into three groups： group A (normal control group, n=6), group B (emphysema group, passive cigarette smoking for 1 hour twice everyday for 13 months, 0.1 ml PBS by tracheal instillation on day 361, n=6), group C (emphysema + MHV-68 group, 1×105 plaque forming units of MHV-68 in 0.1 ml PBS by tracheal instillation on day 361, n=24), and the group C were further divided into four groups： group C1 (sacrificed on day 367, on day 7 after MHV-68 tracheal instillation, n=6)； group C2 (sacrificed on day 374, on day 14 after MHV-68 tracheal instillation, n=6)； group C3 (sacrificed on day 381, on day 21 after MHV-68 tracheal instillation, n=6)； group C4 (sacrificed on day 388, on day 28 after MHV-68 tracheal instillation, n=6).Group A and B were sacrificed on day 388.The bronchoalveolar lavage fluid (BALF) and lung specimens were collected. Secondly, another group of experimental mice were randomly divided into five groups： normal control group； pcDNA3.1 control group； pcDNA3.1-MUC5AC group； CPFE group； pcDNA3.1-MUC5AC+CPFE group.Morphometric analysis of each group was investigated by hematoxylin and eosin staining, and masson trichrome staining.MHV-68 gp150 mRNA was detected by real-time PCR.MUC5AC levels in lung tissues were analyzed by immunohistochemical staining, real-time PCR and western blotting.The airway inflammations were determined by differential cell counts of broncho - alveolar lavage fluid (BALF) and measurement of cytokines and chemokines in BALF with enzyme-linked immunosorbent assay.结果 Conspicuous broken and merged alveolar walls and enlarged cavities of alveoli were observed in Emphysema + MHV-68 group.Emphysema + MHV-68 group mice showed developed severe pneumonitis with collagen deposition indicated by blue staining which persisted as a patchy interstitial fibrosis.The inflammation and fibrosis were detectable in the day-7 subgroup and reached a peak in the day-28 subgroup.Significantly increased levels of inflammatory cells and MHV-68 gp150 mRNA were found in emphysema + MHV-68 group in BALF and lung tissue respectively.MUC5AC hypersecretion alone was not sufficient to cause obvious mucus plugging, drive goblet cell metaplasia and airway inflammation.However, MUC5AC overexpression serves as a protective barrier against MHV-68 virus infection in vivo.Infectivity of MHV-68 was decreased in pcDNA3.1-MUC5AC+CPFE group compared with CPFE group.Meanwhile, a diminution of MHV-68 virus attenuated the expression of CCL2, CXCL5, IL-13 and TGF-β1, and weakened airway inflammation and fibrosis in pcDNA3.1-MUC5AC+CPFE group.结论 MHV-68 could induce long time cigarette smoke-induced old male emphysema mice developed into CPFE mice model.Increased MUC5AC appears to exhibit a protective role against MHV-68 infection during emphysema mice developed into CPFE mice and further weakens airway inflammation and fibrosis induced by MHV-68 by decreasing the expression of CCL2, CXCL5, IL-13 and TGF-β1.