| Objective:To study the effects of rosiglitazone on TGF-β1, caspase-3 and airway remodeling in asthmatic rats. Asthma rat model was established successfully. The expression level of TGF-β1, caspase-3 in lung tissue and serum were detected in the asthma group. Through comparing the differences of TGF-β1, caspase-3,airway wall thickness between rosiglitazone intervention group and asthma group, we investigate the effects of rosiglitazone on asthma airway remodeling.Method: Thirty three cleaning SD rats(female, six weeks, and weight from 120 to 150 grams) were randomly divided into three groups: control group, asthma group and rosiglitazone intervention group. Each group has 10 rats. The asthma group rats were sensitized on the first day and the 8th day with ovalbumin(100mg) and AL(OH)3(100mg) by intraperitoneal injection(mixed in normal saline 2ml). And then these rats were inhaled aerosolized OVA in a close box from the 15 th day. We adjusted the concentration according to the rats’ symptoms. The rats were inhaled 30 minutes each challenge. They were total 20 times and each challenge at 48-hours intervals. The successfully challenged rats were showed such as uneasy, cough, shortness of breath, and less activity. The rosiglitazone intervention group rats received 5 mg/kg rosiglitazone by gavage 30 minutes before OVA challenge. And the rosiglitazone intervention group challenge process was the same as the asthma group. In the control group, rats were challenged by the process same as the asthma group and the rosiglitazone intervention group but using only normal saline replace OVA. After 24 hours of last challenge, rats were anesthesiaed by 1% pentobarbitalin and sacrifice. The numbers of total cells, neutrophils, lymphocytes and eosinophils in the BALF were counted. Lung tissues were sliced and stained with HE. The expressions of caspase-3 in lung tissues were observed by immunohistochemistry combined with the micro-image analysis, and mean optical densities of caspase-3 were measured by image analysis software. The contents of TGF-β1 in serum were measured by ELISA. The makers such as the airway wall thickness and airway smooth muscle thickness were measured by image analysis software. Using SPSS statistical method, determination the correlation between the asthma bronchial wall thickness in mice and caspase3 expression in lung tissue, TGF –β1 expression in serumand.Results:1 Results of total cells and eosinophils in the BALF(×106):The numbers of total cells and eosinophils in the BALF in the three groups were as follows: Control group were9.49±0.10, 0.52±0.08. Asthma group were 35.21±0.51, 3.53±0.06. Rosiglitazone intervention group were 14.98±0.67, 1.27±0.06. The asthma group were significantly more than the rosiglitazone intervention group(P<0.01), and all the cells were significantly more than that in the control group(F=7563.975, P<0.01; F=5294.103, P<0.01).2 Pathological findings: The obvious inflammatory cells infiltration, goblet cells and smooth muscle cells proliferation, vascular hyperplasia, airway wall thickness were observed in the asthma group. The pathological changes in the lung tissue of rosiglitazone intervention group were all better than the asthma group and were not observed in the control group.3 Results of image analysis: The airway wall thickness(μm2/μm) and the thickness of smooth muscle(μm2/μm) in the asthma group(98.49±2.58; 45.29±2.26) were significantly more than the rosiglitazone intervention group(86.03±2.63; 33.54±1.35)(P<0.01). The airway wall thickness and the thickness of smooth muscle in the two groups were significantly more than the control group(70.75±2.10; 17.62±1.12)( F=323.150, P<0.01; F=704.562, P<0.01).4 Results of immunohistochemistry: The expression levels of caspase-3 in lung of the asthma group(0.0789±0.0529) were significantly lower than the rosiglitazone intervention group(0.1429±0.0435)(P<0.01). The expression levels of caspase-3 in lung of the two groups were also significantly lower than the control group(0.2499±0.0835)(F=19.219, P<0.01).5 Result of ELISA: The content of TGF-β1(ng/ml)in serum of the asthma group(30.63±1.76)was significantly higher than the rosiglitazone intervention group(23.57±0.97)(P<0.01). The contents of TGF-β1 in serum of the two groups were significantly higher than the control group(17.13±1.13)(F=257.16, P<0.01).6 Results of correlation analysis: There was a significant negative correlation between the airway wall thickness and the expression levels of caspase-3(r=-0.782, P<0.01). There was also a significant positive correlation between the content of TGF-β1 in serum and the airway wall thickness(r=0.986, P<0.01). There were significant negative correlations between the expression levels of caspase-3 in lung and the content of TGF-β1 in serum(r=-0.771, P<0.01).Conclusion:1 We observed obviously inflammatory cells infiltration in lung tissue of the asthma group. It demonstrated that bronchial asthma is a chronic airway inflammatory disease which usually has various inflammatory cells participated. And rosiglitazone can obviously reduce the airway inflammation.2 rosiglitazone can obviously relieve asthma gland hyperplasia in rat lung tissue, airway wall thickening, and other pathological changes, also can significantly reduce airway wall thickness and the thickness of the airway smooth muscle, The airway wall thickness was significantly positively related to the thickness of smooth muscle, and rosiglitazone can obviously relieve the airway remodeling.3 The expression levels of caspase-3 in rosiglitazone group is higher than asthmatic group. The expression levels of TGF-β1 in asthmatic group and rosiglitazone group were obviously increased. The expression levels of TGF-β1 in rosiglitazone group is lower than asthmatic group. The rosiglitazone inhibits the activity and expression of TGF-β1 and can increase the expression of caspase-3.4 The results of correlation analysis showed significant negative correlation between the expression level of caspase-3 and the bronchial wall thickness.positive correlation between the expression level of TGF-β1 and the bronchial wall thickness. Rosiglitazone reduce airway remodeling,inhibitory activity and expression of TGF-β1and can increase the expression of caspase-3.And to relieve airway inflammation and airway remodeling. |
