Effect of fluvastatin on airway remoª²deling in asthmatic rats and its mechanism

    WANG Li, WU Changª²Gui, NI Dianª²Tao, CHEN Hongª²Qian

    Department of Respiratory Diseases, Xijing Hospital, Fourth Military Medical University, Xi¬ðan 710033, China

    ¡¾Abstract¡¿ AIM: To investigate the effect of hydroxyª²methylglutarylª²CoA (HMGª²CoA) reductase inhibitor, fluvastatin, on airway remodeling in asthmatic rats. METHODS: The male Spragueª²Dawly rats were randomly divided into 5 groups with 10 rats in each group: the normal control group (A), the model group (B), the dexamethasone treated group (C), the fluvastatin treated group (D), and the dexamethasone and fluvastatin treated group (E). The asthmatic rat model was established by intraª²peritoneal injection and repeated inhalation of 10 g/L ovalbumin. The changes of collagen type ¢ó , proliferation cell nuclear antigen (PCNA) and P21ras contents in the airway wall were detected by immunohistochemistry, and the internal perimeter of bronchi (Pi) and the area of bronchial smooth muscle (WAm) were measured by the computerized image analysis system. RESULTS: ¢ÙFluvastatin inhibitated the proliferation in airway remodeling: The WAm/Pi [(4.44¡À0.95) ¦Ìm2/¦Ìm], the contents of collagen type ¢ó (32¡À6) and PCNA (38¡À10) in group D were lower than those in group B [(7.01¡À1.54) ¦Ìm2/¦Ìm, 55¡À8, 68¡À12], the difference being significant (all P<0.05); ¢ÚFluvastatin was less effective in inhibition on the course of airway remodeling than dexamethasone and dexamethasone and fluvastatin combination : The WAm/Pi, the contents of collagen type ¢ó and PCNA in group D were higher than those in group C [(3.14¡À1.06) ¦Ìm2/¦Ìm, 21¡À6, 26¡À6] and group E [(3.03¡À0.87) ¦Ìm2/¦Ìm, 20¡À7, 25¡À7] respectively, the difference being significant (all P<0.05). ¢ÛThe contents of P21ras in group D (24¡À11) were lower, as compared with group B (57¡À10, P<0.05). A close correlation was demonstrated between P21ras and PCNA (rs=0.685, P<0.05). The same positive correlation was found between P21ras and collagen type ¢ó (rs=0.530, P<0.05). CONCLUSION: Fluvastatin could delay the course of airway remodeling in asthmatic rats, which is related partly to the inhibition on P21ras. But the inhibition of fluvastatin on the course of airway remodeling is less effective than the inhibition of dexamethasone. ......