PDF(Pubmed)
Abstract：
The efficacy of rosuvastatin in reducing allergic inflammation has been established. However, its potential to reduce airway remodeling has yet to be explored. This study aimed to evaluate the efficacy of rosuvastatin in reducing airway inflammation and remodeling in a mouse model of chronic allergic asthma induced by sensitization and challenge with OVA. Histology of the lung tissue and the number of inflammatory cells in bronchoalveolar lavage fluid (BALF) showed a marked decrease in airway inflammation and remodeling in mice treated with rosuvastatin, as evidenced by a decrease in goblet cell hyperplasia, collagen deposition, and smooth muscle hypertrophy. Furthermore, levels of inflammatory cytokines, angiogenesis-related factors, and OVA-specific IgE in BALF, plasma, and serum were all reduced upon treatment with rosuvastatin. Western blotting was employed to detect AMPK expression, while immunohistochemistry staining was used to observe the expression of remodeling signaling proteins such as α-SMA, TGF-β, MMP-9, and p-AMPKα in the lungs. It was found that the activity of 5\'-adenosine monophosphate-activated protein kinase alpha (AMPKα) was significantly lower in the lungs of OVA-induced asthmatic mice compared to Control mice. However, the administration of rosuvastatin increased the ratio of phosphorylated AMPK to total AMPKα, thus inhibiting the formation of new blood vessels, as indicated by CD31-positive staining mainly in the sub-epithelial region. These results indicate that rosuvastatin can effectively reduce airway inflammation and remodeling in mice with chronic allergic asthma caused by OVA, likely due to the reactivation of AMPKα and a decrease in angiogenesis.
摘要：
瑞舒伐他汀在减少过敏性炎症方面的功效已经确立。然而,其减少气道重塑的潜力还有待探索.本研究旨在评估瑞舒伐他汀在OVA致敏和攻击诱导的慢性过敏性哮喘小鼠模型中降低气道炎症和重塑的疗效。肺组织的组织学和支气管肺泡灌洗液（BALF）中的炎症细胞数量显示，在接受瑞舒伐他汀治疗的小鼠中，气道炎症和重塑明显减少，正如杯状细胞增生减少所证明的那样，胶原蛋白沉积，和平滑肌肥大.此外，炎症细胞因子的水平，血管生成相关因子,BALF中OVA特异性IgE，等离子体,瑞舒伐他汀治疗后，血清均降低。采用蛋白质印迹法检测AMPK表达,免疫组化染色观察α-SMA等重塑信号蛋白的表达,TGF-β,肺中的MMP-9和p-AMPKα。发现与对照小鼠相比，OVA诱导的哮喘小鼠的肺中5'-一磷酸腺苷活化的蛋白激酶α（AMPKα）的活性显着降低。然而,瑞舒伐他汀的给药增加了磷酸化AMPK与总AMPKα的比例，从而抑制新血管的形成，如CD31阳性染色所示，主要在上皮下区域。提示瑞舒伐他汀可有效减轻OVA所致慢性过敏性哮喘小鼠的气道炎症和重塑,可能是由于AMPKα的再激活和血管生成的减少。
