丹参酮对肺纤维化大鼠的干预作用及其机制研究

摘要

目的：观察丹参酮对博莱霉素致大鼠肺纤维化的影响及其作用机制。方法：SD 大鼠随机分为5组：空白对照组、模型组、地塞米松阳性对照组、丹参酮组、丹参酮加地塞米松组。大鼠气管内注射博莱霉素复制肺纤维化模型后，各给药组腹腔注射相应药物，给药1次／d。28 d 后处死动物，取固定部位肺组织分别行 HE、Masson 染色及电镜进行病理组织学检查；RT-PCR 法检测丹参酮对大鼠肺组织中 uPA、PAI-1 mRNA 表达的影响。结果：与模型组相比，丹参酮组大鼠肺泡炎和肺纤维化程度明显减轻（P ＜0.05，0.01）；uPA 显著升高而 PAI-1表达明显降低（P ＜0.05，0.01）；在与地塞米松联合时以上作用更加明显。结论：丹参酮对博莱霉素所致大鼠肺纤维化具有一定的治疗作用且与地塞米松有协同作用，其机制可能与抑制炎性反应细胞的浸润活化、细胞外基质沉积及调控 UPA 及 PAI-1之间平衡有关。%Objective:To investigate the effect of Tanshinone on urokinase-type plasminogen activator(uPA)and urokinase-type plas-minogen activator-1 (PAI-1)in rats with pulmonary fibrosis and to explore the possible mechanism.Methods:Fifty Spague-Dawley rats were randomly divided into the control group,model group,Tanshinone group,dexamethasone groupand Tanshinone add dexamethasone group.The rats of model group and the treatment group were induced pulmonary fibrosis with bleomycin(5 mg /kg)endotracheally, while the rats of other groups were given normal saline instead.After 28 days,rats with Tanshinone treatment by Intraperitoneal injection administration once a day were killed.The rat lung histopathology was examined with HE staining,masson staining and electron micro-scope.The influences of Tanshinone on the expression of uPA and PAI-1 mRNA in lung tissue of rats with Bleomycin-induced pulmonary fibrosis were assayed by RT-PCR.Results:Compared with the model group,the alveolitis and fibrosis extent were attenuated after Tanshi-none treatment (P <0.05,0.01),and the expression levels of uPA was increased and PAI-1 mRNA was decreased (P <0.05,0.01) significantly.Compared with the dexamethasone group,therapeutic effect was more obviously when Tanshinone combine with dexametha-sone(P <0.01).Conclusion:Tanshinone has a good action against experimental pulmonary fibrosis and has the synergetic effect with dexamethasone.The mechanisms might be related to the inhibition of activation of inflammatory cell infiltration,collagen deposition and regulation of equilibrium between the uPA and PAI-1.