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氟伐他汀对哮喘大鼠气道重建的影响及其机制
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作者：王立, 吴昌归,倪殿涛, 陈宏谦
【关键词】 氟伐他汀;,支气管哮喘;,气道重建;,癌基因蛋白质p21(ras)
Effect of fluvastatin on airway remodeling in asthmatic rats and its mechanism
【Abstract】 AIM: To investigate the effect of hydroxymethylglutarylCoA (HMGCoA) reductase inhibitor, fluvastatin, on airway remodeling in asthmatic rats. METHODS: The male SpragueDawly 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 intraperitoneal injection and repeated inhalation of 10 g/L ovalbumin. The changes of collagen type Ⅲ , 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: ①Fluvastatin inhibitated the proliferation in airway remodeling: The WAm/Pi ［(4.44±0.95) μm2/μm］, the contents of collagen type Ⅲ (32±6) and PCNA (38±10) in group D were lower than those in group B ［(7.01±1.54) μm2/μm, 55±8, 68±12］, the difference being significant (all P<0.05); ②Fluvastatin 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 Ⅲ and PCNA in group D were higher than those in group C ［(3.14±1.06) μm2/μm, 21±6, 26±6］ and group E ［(3.03±0.87) μm2/μm, 20±7, 25±7］ respectively, the difference being significant (all P<0.05). ③The contents of P21ras in group D (24±11) were lower, as compared with group B (57±10, 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 Ⅲ (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.
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