| Objective: Pendrin is a PDS encoding protein exchanging anions like iodide, chloride and bicarbonate. Recently research found that pendrin may play a major role in the pathogenesis of asthma, especially in the pathogenesis of mucus hypersecretion. Evidences are now emerging of the potential benefits of pioglitazone, a PPARγ ligand, in inflammatory airways disease, such as COPD and asthma, but the relation between expression of pendrin on airwayin asthma and dexamethasone or pioglitazone has been reported little. This study plans to establish the mouse models of asthma, to treat them with dexamethasone or pioglitazone, then to observe expression of pendrin and MUC5 AC in the airway, and illuminates the effects of dexamethasone or pioglitazone on expression of pendrin. Methods: Female BALB/c mice(4–6 wk. old) were divided into 4 groups: PBS group, OVA group, pioglitazone group and dexamethasone group. Mice were sensitized by two i.p. injections on day 1 and day 8, and challenged seven times intranasally on day 22 to day 29. Mice from pioglitazone group and dexamethasone group were treated by i.g. injections(pioglitazone) or i.p. injections(dexamethasone) 30 min before every challenge. Control animals received PBS alone. Twenty-four hours after the last exposure to allergen, mice were sacrificed, and histopathologic examination were performed; bronchoalveolar lavage(BAL) was performed to count cellnumbers; OVA-specific antibody responses and IL-4 or IL-13 levels in BAL F were evaluated using ELISA; IHC or q PCR was used to evaluate the expression of pendrin or MUC5 AC in lung. Results:(1)HE staining: There are no obvious inflammatory cells infiltration around airways, and the airway epithelial cells are intact as well as the goblet cells are little in the control group. In mice of OVA group, a large number of inflammatory cells infiltrate in the lung, and hyperplasia are found in goblet cells as well as necrosis are found in the airway epithelial cells. In addition, lumen are jammed by mucus plug sometimes. And all these pathological changes are alleviated by treatment of pioglitazone or dexamethasone.(2)Cell amounts in BAL F: Comparing with PBS group, amounts of leukocyte(p<0.01) and eosnophils(p<0.01) are higher in the OVA group, while treatment of pioglitazone or dexamethasone reduce these cell numbers(all p<0.01).(3) OVA-s Ig E levels: OVA-s Ig E levels of OVA group are higer than PBS group(p<0.01), and are also higher than pioglitazone group(p<0.01) or dexamethasone group(p<0.01).(4)IL-4 and IL-13 levels in BAL F: Comparing with PBS group, IL-4 and IL-13 levels in BAL F are higher in the OVA group(p<0.01), while treatment of pioglitazone or dexamethasone decrease IL-4 and IL-13 levels(p<0.01).(5)IHC: There are little expression of pendrin and MUC5 AC in PBS group. Plenty of positive staining cells are found in OVA group, while the positive staining cells are less in the pioglitazone group or dexamethasone group.(6)q PCR: m RNA of pendrin or MUC5 AC in lung of mice from the OVA group are higher than PBS group(p<0.01).Aftertreatment of pioglitazone or dexamethasone, m RNA of pendrin or MUC5 AC are reduced(p<0.01). Conclusions:(1)The expression of pendrin and MUC5 AC are higher in OVA induced mice, and There is a positive correlation between pendrin and MUC5 AC. Thus, pendrin may play a major role in the pathogenesis of mucus hypersecretion.(2) Pioglitazone or dexamethasone has effectively therapeutical effect on inflammatory cells infiltration and Th2 cytokine secretion, and can down-regulate the expression of pendrin as well as suppress the expression of MUC5 AC. Consequently, to inhibit the expression of pendrin may be one of the mechanism of the two treatment to reduce mucus hypersecretion in allergic mice. |
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