Objective To investigate protective effect of Resveratrol combined with Irbesartan on Bleomycin-induced pulmonary fibrosis in rats and its mechanism.Methods A total of 108 male rats were divided into group A,B and C (n =36 for each group) according to random number table method.All rats were treated with Bleomycin to establish pulmonary fibrosis models.After the models establishment,group A was lavaged with physiological saline;group B was lavaged with Irbesartan;group C was lavaged with Resveratrol on the basis of treatment for group B.After treatment for 3 days,expressions of serum transforming growth factor-β1 (TGF-β1),a disintegrin-like and metalloproteases with thrombospondin type 1 motif (ADAMTS-1),collagen type Ⅰ (Col Ⅰ),collagen type Ⅲ (Col Ⅲ),serum procollagen type Ⅰ carboxy terminal propeptide (P Ⅰ CP),type Ⅲ n-terminal procollagen (PⅢ NP),serum tumor necrosis factor-α (TNF-α),interleukin-6 (IL-6) and IL-17,and contents of hydroxyproline (HYP),malondialdehyde (MDA),superoxide dismutase (SOD),glutathione peroxidase (GSH-Px) and catalase (CAT) in lung tissues were compared among the three groups.Results In group B and C,levels of TGF-β1,Col Ⅰ,ColⅢ,HYP,SOD,GSH-Px and CAT were significantly increased,while ADAMTS-1,P Ⅰ CP,PⅢNP,TNF-α,IL-6,IL-17 and MDA levels were significantly decreased compared with those in group A;in group C,ADAMTS-1,Col Ⅰ,Col Ⅲ,HYP,SOD,GSH-Px and CAT levels were significantly higher,while TGF-β1,P Ⅰ CP,PⅢ NP,TNF-α,IL-6,IL-17 and MDA levels were significantly decreased compared with those in group B (P ＜ 0.05).Degrees of alveolar inflammation and pulmonary fibrosis in group B and C were slighter than those in group A,and the degrees in group C were slighter than those in group B (P ＜ 0.05).Conclusion Resveratrol combined with Irbesartan has a certain protective effect on pulmonary interstitial tissue in rats with pulmonary fibrosis.It is possible to increase ADAMTS-1 content by decreasing TGF-β1 level and reducing Col Ⅰ and Col Ⅲ levels in order to have an anti-fibrosis effect.%目的 探讨白藜芦醇联合厄贝沙坦对博莱霉素所致大鼠肺纤维化肺组织的保护作用及作用机制.方法 108只雄性大鼠,按随机数字表法分为A、B和C组,每组36例.3组均予博莱霉素制备肺纤维化模型,模型建立成功后A组予生理盐水灌胃,B组予厄贝沙坦灌胃,C组在B组基础上给予白藜芦醇灌胃,治疗7d后比较3组血清转化生长因子(TGF-β1)、解聚蛋白样金属蛋白酶(ADAMTS-1)、Ⅰ型胶原(Col Ⅰ)、Ⅲ型胶原(Col Ⅲ)及血清Ⅰ型前胶原羧基端肽(PI CP)和Ⅲ型前胶原氨基端前肽(PⅢNP)、血清肿瘤坏死因子-α(TNF-α)、白介素(IL)-6、IL-17的表达水平、肺组织羟脯氨酸(HYP)、丙二醛(MDA)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)及过氧化氢酶(CAT)含量.结果 B、C组ADAMTS-1、Col Ⅰ、ColⅢ、HYP、SOD、GSH-Px及CAT均较A组升高,TGF-β1、PⅠCP和PⅢNP、TNF-α、IL-6、IL-17、MDA较A组降低,C组ADAMTS-1、Col Ⅰ、ColⅢ、HYP、SOD、GSH-Px及CAT高于B组,TGF-β1、PⅠ CP和PⅢNP、TNF-α、IL-6、IL-17、MDA水平低于B组(P＜0.05).B、C组肺泡炎症及肺纤维化程度轻于A组,且C组轻于B组(P＜0.05).结论 白藜芦醇联合厄贝沙坦对肺纤维化大鼠的肺组织具有一定的保护作用,其可能通过降低TGF-β1水平使ADAMTS-1含量升高,降低Col Ⅰ和ColⅢ水平从而起到抗纤维化的作用.
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