Effects Of Vasoactive Intestinal Peptide On Mucins Secretion Of Ozone Stressed Rat Lungs And Bronchial Epithelial Cells

Objective:Airway hyperresponsiveness (AHR) diseases show a cluster of pathologic changes including airway epithelial cells shedding, inflammatory cells infiltration and excessive secretion of mucus. Airway mucus is a lipid, carbohydrate and protein conjugate gel, high molecular weight mucus glycoprotein (also known as mucin, mucins, MUC) is the most important component of airway mucus with high viscosity nature and difficult to be cleared. Airway obstruction by high production and secretion of mucus is one of the consistent features of asthma, therefore, the role of mucus in AHR disease become a research focus in recent years. Vasoactive intestinal peptide (VIP) is a neuropeptide with potent bronchodilator, immunomodulator, and anti-inflammatory properties, and thus has biological properties capable of counteracting all major features of the asthmatic response. Based on our previous studies, we damaged the airway epithelium with ozone stress in animal to construct an AHR model and observed the expression of lung tissue and bronchial epithelial cells of three mucins:MUC1, MUC2, MUC5AC, and observed the impact of VIP on these three types of mucins.Methods:The lung tissue experiments:40 SD rats were randomly divided into four groups:control group, ozone stress group, ozone stress plus VIP intranasal treatment group and the ozone stress plus saline nasal treatment group, n= 10. (1)Detect the expression of three types of mucin (MUC1, MUC2, MUC5AC) after ozone exposure and the effect of VIP on their expression by immunohistochemistry. (2)Detect the expression of three types of mucin (MUC1, MUC2, MUC5AC) after ozone exposure and the effect of VIP on their expression by western-blot. Cell level experiment:Cultured SD rats bronchial epithelial cells were divided into four groups:control group, ozone stress group, ozone stress plus VIP intranasal treatment group and the ozone stress plus saline nasal treatment group. Western-blot were used to detect the expression of MUC1, MUC2, MUC5AC after ozone exposure and the effect of VIP on bronchial epithelial cell mucin expression.Results:The results showed that the expression of MUC5AC was lower than MUC2 and MUC1 both in rat lung tissue and rat bronchial epithelial cells. After 8 days of ozone stress, MUC2,MUC1 and MUC5AC expression were significantly increased. VIP treatment could decrease the MUC2 and MUC5AC level, but with no use of MUC1.Conclusion:Airway mucus hypersecretion during the ozone stress may be related to the upregulation of MUC2 and MUC1, VIP could inhibited the excessive secretion of airway mucus through decrease the MUC2 and MUC5AC expression.