Involvement of alpha-7 nicotinic receptor (α7nAChR) in respiratory syncytial virus infection-induced asthma in rats

Abstract

This study aimed to investigate the role of alpha−7 nicotinic receptor (α7nAChR) in rats with asthma caused by respiratory syncytial virus (RSV) infection. An asthmatic rat model was established by RSV infection and confirmed based on pathological changes. sh-α7nAChR lentivirus was constructed to reduce α7nAChR expression in rats. The animals were divided into a control group, a model group, a sh-α7nAChR lentivirus group, a nerve growth factor (NGF) antibody group, a dexamethasone (DXMS) group, a sh-α7nAChR lentivirus + NGF antibody group, and a sh-α7nAChR lentivirus + DXMS group. The expression of α7nAChR was detected by quantitative real-time PCR and western blotting. Serum levels of adrenaline and norepinephrine were detected by ELISA. Transmission electron microscopy determined the morphological change of chromaffin cells and synaptic vesicles. Immunofluorescence was used to detect the expression of synaptophysin (SYN) and nuclear factor-kappa B (NF-κB). Compared with the control group, the model group showed significantly increased expression of α7nAChR, SYN, and NF-κB. Compared with the model group, the sh-α7nAChR lentivirus, NGF antibody, DXMS, sh-α7nAChR lentivirus + NGF antibody, and sh-α7nAChR lentivirus + DXMS groups showed significantly decreased expression of α7nAChR (P < 0.05). After repeated infection with RSV, the number of chromaffin cells and synaptic vesicles increased, which were significantly reduced after silencing α7nAChR by NGF antibody or DXMS treatment. The model group showed significantly lower serum adrenaline than the control group (P < 0.05). Similarly, the serum adrenaline in the sh-α7nAChR lentivirus, sh-α7nAChR lentivirus + NGF antibody, and sh-α7nAChR lentivirus + DXMS groups, but not the NGF antibody and DXMS groups, was significantly lower than in the model group. Together, upregulation of α7nAChR is involved in RSV infection-induced asthma in rats. Silencing of α7nAChR reduces the numbers of chromaffin granules and synaptic vesicles and adrenaline release.