| Background:The bronchial asthma is a chronic airway inflammatory disease in which eosinophils, mast cells and T lymphocytes and other inflammatory cells and cellular element play a role. Peroxisome proliferator-activated receptor gamma (PPAR-y) is one member of ligand-activated nuclear receptor transcription factor PPAR family and Its ligands, including steroids, vitamin D, thyroid hormone, retinoic acid receptors et al. Previous studies have shown that PPAR-y mainly involved in the regulation of insulin-sensitive sugar and fat metabolism. Recent studies have found that PPAR-y was expressed in inflammatory cells, airway epithelium, bronchial submucosa and airway smooth muscle and has a role in inhibiting inflammation, inducing cell differentiation, inhibiting cell proliferation and inducing cell apoptosis. The signaling pathways related to PPAR-y play an important role in regulation of acute lung injury, chronic lung disease, pulmonary hypertension and pulmonary fibrosis. PPAR-γagonist can reduce airway inflammation in allergic asthma of mice by affecting eosinophils, T lymphocytes, dendritic cells and lung epithelial cells. BCG (BCG) is a attenuated live vaccine obtained from Mycobacterium tuberculosis that cultured for 230 generation, and mainly used for prevention and cure of tuberculosis. Many studies shown that the BCG vaccine plays an important role in immunomodulatory effects of asthma and allergic diseases and could induce Th1 immune responses, increase Th1 response and inhibit Th2 cell function, which may be related to the production of IFN-y and the low level of IL-4, IL-5 induced by BCG. But it has rarely reported that the effect and its significance of BCG intervention on the expression of PPAR-γin the lung tissue of asthmatic mice.Objective:Through the establishment of mouse asthma model, the asthma mice were given to the treatment of BCG vaccination, and observe the effect of BCG on the expression of peroxisome proliferator-activated receptor-y (PPAR-γ) in the lung tissue of asthmatic mice and its significance.Methods:Tewnty-four male Kunming mice were randomly divided into three groups:normal control group (A group), asthma model group (B group) and BCG treatment group (C group). We establish the asthma model of mice by sensitizing with ovalbumin. The general situation of mice in three groups was observed. Cell types in BALF were detected. Pathological changes in lungs were analyzed. Expressions of PPAR-y mRNA ans protein were measured with RT-PCR and western blotting.Results:1. BALF examination revealed: Number of total leukocytes and number of neutrophils, eosinophils and lymphocytes in BALF of asthma model group (B group) were significantly higher than normal control group (A group) (P<0.01). Number of total leukocytes and number of neutrophils and eosinophils in BALF of BCG treatment group (C group) were abviously lower than asthma model group (B group) (P<0.05).2. Pathological examination revealed:Pathological analysis of the lung showed that normal control group (A group) almost no inflammatory cell infiltration, and asthma model group (B group) a large number of inflammatory cells infiltration and was significantly higher than normal control group (A group) (P<0.01). BCG treatment group (C group) had lower inflammatory cells infiltration than asthma model group (B group) (P<0.05).3. RT-PCR results revealed:The level of PPAR-y mRNA in lung tissue of normal control group (A group) was high expressed. After the success of induced asthma model, the level of PPAR-y mRNA in lung tissue of asthma model group (B group) was significantly lower (P<0.01). Compared with the asthma model group (B group), the level of PPAR-y mRNA in lung tissue of BCG treatment group (C group) was significantly increased (P<0.05).4. Western blotting results revealed: The level of PPAR-y protein in lung tissue of normal control group (A group) was high expressed. After the success of induced asthma model, the level of PPAR-y protein in lung tissue of asthma model group (B group) was significantly lower (P<0.01). Compared with the asthma model group (B group), the level of PPAR-y protein in lung tissue of BCG treatment group (C group) was significantly increased (P<0.05).5. The analysis of correlation indicated:Neutrophils number of BALF in asthma model group (B group) was significantly positive correlation with airway inflammation (r=0.934, P< 0.01); The level of peroxisome proliferator-activated receptor (PPAR-y) protein expression in asthma mouse model group (B) was significantly negative correlation with airway inflammation (r=-0.954, P<0.01), and was significantly negative correlation with neutrophils number of BALF (r=-0.900,P<0.01).Conclusion:1. Expression of PPAR-y in lung tissue significantly decreased and negatively correlated with airway inflammation in the mouse model of bronchial asthma.2. Treatment of BCG reduced the expression of PPAR-y in the lung tissue of asthmatic mice, and reduced number of total leukocytes and number of neutrophils and eosinophils in BALF. 3. BCG reduced infiltration of inflammatory cells and inhibited the inflammatory response to prevent airway remodeling by up-regulating the expression of PPAR-y and activating the signaling pathway of PPAR-γ. |
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