【摘 要】
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Aldose reductase(AR)is known to play a crucial role in the mediation of diabetic and cardiovascular complications.Recently,several studies have demonstrated that allergen-induced airway remodeling and
【机 构】
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Department of Pharmacology,Wannan Medical College,Wuhu 241002,China
【出 处】
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第一届《药学学报》药学前沿论坛暨2015年中国药学会中药与天然药物专业委员会会议
论文部分内容阅读
Aldose reductase(AR)is known to play a crucial role in the mediation of diabetic and cardiovascular complications.Recently,several studies have demonstrated that allergen-induced airway remodeling and ovalbumin-induced asthma is mediated by AR.Epalrestat(EPS)is an aldose reductase inhibitor that is currently available for the treatment of diabetic neuropathy.Whether AR is involved in pathogenesis of pulmonary fibrosis and whether epalrestat attenuates pulmonary fibrosis remains unknown.Pulmonary fibrosis was induced by intratracheal instillation of bleomycin(5 mg·kg-1)in rats.Primary pulmonary fibroblasts were cultured to investigate the proliferation by BrdU incorporation method and flow cytometry.The expression of AR,TGF-β1,α-SMA and collagen I was analyzed by immunohistochemisty,real-time PCR or western blot.Results showed that the expression of AR was obviously increased in lungs of pulmonary fibrosis rats.In cultured pulmonary fibroblasts,application of exogenous TGF-β1 induced cell proliferation and differentiation concomitantly with up-regulation of AR expression,and these effects were abolished by AR siRNA.EPS treatment decreased bleomycin-induced AR,α-SMA and collagen I expression,and subsequently attenuated bleomycin-induced pulmonary fibrosis.EPS also remarkably attenuated pulmonary fibroblasts proliferation and AR,α-SMA and collagen I expression induced by TGF-β1 in vitro.These findings suggest that AR plays an important role in bleomycin-induced pulmonary fibrosis,and EPS inhibited the progression of bleomycin-induced pulmonary fibrosis is mediated via inhibiting of AR expression.
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