| Objective: To investigate the effect both leukotriene receptor antagonist and CyclinD1 on airway remodeling in the rat asthma model. To study the influence and potential mechanism both leukotriene receptor antagonist and CyclinD1 effect on airway remodeling.Method: This study consists of two parts. The first part: twenty-four SD rats were randomly divided into four groups. A: normal control group, B: asthma model group, C: dexamethasone group, D: montelukast group. SD rats were sensitized by Injection with ovalbumin, Bacillus Calmette-Guerin Vaccine and AL(OH)3 on the first day and the 8th day ,then they were challenged with repeated exposure to aerosolized ovalbumin to established asthmatic model. Pulmonary function was measured in 24 hours after the last challenge (the airway basic expiratory resistance and airway expiratory resistance after injected Ach). The lung tissue sections were stained with HE and Manssion staining method. Then we measured the airway internal perimeter, airway wall area, area of smooth muscle by optical microscope and image analysis system. The LTD4 level in serum was measured by ELISA. The expression ofα-SMA was measured by immunohistochemical method.The second part: twelve SD rats were randomly divided into two groups. A: normal control group, B: asthma model group. Duplicating the asthmatic model according to the method as before. The lung tissue sections were stained with HE and Manssion staining, The CyclinD1 in lung was measured with both immunohistochemical method and Western blotting methed.The expression ofα-SMA was measured by immunohistochemical method. We studyed the correlation between CyclinD1 andα-SMA,collegan by turns. Result of the first part:(1) The influence of the leukotriene receptor antagonist effect on lung in pathological observation: The airway mucosa was damaged, caliciform cell increasing, inflammatory cells infiltrating below mucosa, RBM thickening, the smooth cell proliferating in asthma and treatment groups through optical microscope. Those in dexathasone and mentelukaet groups were better than asthma group. Then we compared the airway internal perimeter, wall area and area of smooth muscle by optical microscope and image analysis system: The airway internal perimeter, airway wall area and smooth muscle area were significantly thicker in rats of asthma group than those in control group; the airway wall area, smooth muscle layer were significantly thinner in rats of both dexamethasone and montelukast groups than those in asthma group, but that were thicker than those in control group. It was better in dexamethasone group than those in montelukast group. (2) The influence of the leukotriene receptor antagonist effect on pulmonary function: The airway basic expiratory resistance was higher in asthma and therapy groups than it in control group(P<0.01), it was lower in both dexamethasone and montelukast groups than it in asthma group(P<0.05). it was slightly lower in dexamethasone group than it in montelukast group, but which have not statistics significance(P>0.05). The variety of expiratory resistance was higher in asthma and therapy groups than it in control group after injected Ach( P<0.01 ) ; it was lower in both dexamethasone and montelukast groups than it in asthma group(P<0.01). it was lower in dexamethasone group than it in montelukast group after the last injection(P<0.05).(3)The influence of the leukotriene receptor antagonist effect on the expression of collagen(Manssion staining): The expression of collagen in lung was higher in asthma, dexamethasone and montelukast group rats than it in control group(P<0.01). It was less in dexamethasone and montelukast groups than it in asthma group(P<0.01). it was lower in dexamethasone than that in montelukast group(P<0.01).(4) The influence of the leukotriene receptor antagonist effect on the expression of LTD4: The LTD4 level in blood serum was higher in asthma, dexamethasone and montelukast group rats than it in control group(P<0.05), but the LTD4 level in blood serum in asthma, dexamethasone and montelukast groups have not conspicuous difference(P>0.05). (5) The influence of the leukotriene receptor antagonist effect on the expression ofα-SMA: The expression ofα-SMA in asthma and therapy groups were higher than it in control group( P<0.01 ) , it was lower in both dexamethasone and montelukast groups than that in asthma group(P<0.01),it was lower in dexamethasone than that in montelukast group.Result of the second part:(1) Result of pathological observation: The airway mucosa was damaged, caliciform cell increasing, inflammatory cells infiltrating below mucosa, RBM thickening, the smooth cell proliferating in asthma group rats by optical microscope. Then we compared the airway internal perimeter, airway wall area and smooth muscle area: The airway wall area and smooth muscle area were significantly thicker in asthma group rats than those in control group.(2) Results of the collagen observation: The expression of collagen around airway and blood vessel in lung was significantly higher in asthma group rats than it in control group (P<0.01).(3)Result of the CyclinD1 observation: The expression of CyclinD1 was higher in asthma group rats than it in control group(both immunohistochemical method and Western blotting method)(P<0.01).(4)Result of theα-SMA observation (immunohistochemical method): The expression ofα-SMA in asthma group rats was significantly higher than it in control group(P<0.01).(5)Result of the related analysis: The expression of CyclinD1 (Western blotting method)andα-SMA were positive correlation(r=0.20,P<0.05). The expression of CyclinD1 ( Western blotting method ) and collagen were positive correlation(r=0.87,P<0.05). The expression of CyclinD1 (immunohistochemical method )andα-SMA were positive correlation ( r=0.53 , P<0.05 ) . The expression of CyclinD1(immunohistochemical method ) and collagen were positive correlation(r=0.76,P<0.05).Conclusion: 1.The leukotriene receptor antagonist could significantly relieve the inflammation in airway, improving pulmonary function, lessening collagen deposit, depressing the expression ofα-SMA, but it could not degrade the level of LTD4 in blood serum. Then we presumed that the leukotriene receptor antagonist could improve clinical symptom, relieve the airway remodeling and delay the course in disease.2. The expression of CyclinD1 in asthmat group rats was significantly higher than it in control group. The expression of CyclinD1 and airway remodeling were positive correlation (the expression ofα-SMA and collagen). So, we presumed that the CyclinD1 was playing an important role in airway remodeling.
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