健脾益肺Ⅱ号对熏烟联合脂多糖诱导大鼠炎症因子及金属蛋白酶表达的影响

Influence of Jianpi Yifei II decoction on inflammatory cytokines and metalloproteases in lung tissues of rats induced by cigarette smoke and LPS

[目的]通过观察健脾益肺Ⅱ号对熏烟联合脂多糖诱导的大鼠肺组织基质转化生长因子β1(TGF-β1)、金属蛋白酶-9(MMP-9)和组织金属蛋白酶抑制因子-1(TIMP-1)以及肿瘤坏死因子-α(TNF-α)和白介素(IL-8)表达的影响,以探讨健脾益肺Ⅱ号协调气道损伤、修复平衡以及减少气道重构的作用机制,从而阐明该方防治慢性阻塞性肺疾病(COPD)气道损伤的可能作用机制。[方法]将SD大鼠随机分为正常对照组、模型组、健脾益肺Ⅱ号低剂量组、健脾益肺Ⅱ号高剂量组、泼尼松组。以熏烟联合脂多糖(LPS)的方法建立大鼠肺部损伤模型,给予相应药物干预,观察记录大鼠一般状况,至实验结束,采用免疫组化法比较各组大鼠肺组织MMP-9、TIMP-1的表达水平,采用ELISA法检测大鼠肺组织及血清中TGF-β1的水平变化以及肺组织中TNF-α和IL-8水平的变化。[结果]模型组大鼠肺组织MMP-9、TIMP-1以及MMP-9/TIMP-1的相对表达明显高于正常对照组(P<0.05或P<0.01);健脾益肺Ⅱ号高剂量组和泼尼松组大鼠肺组织MMP-9、TIMP-1以及MMP-9/TIMP-1的相对表达明显低于模型组(P<0.05或P<0.01);模型组大鼠肺组织及血液中TNF-α、IL-8、TGF-β1含量均比正常对照组显著升高(P<0.01),各给药组经过药物的干预后,其含量明显降低(P<0.01或P<0.05)。[结论]健脾益肺Ⅱ号方可通过降低模型动物肺组织MMP-9/TIMP-1相对表达量,下调血清中TGF-β1的水平,降低肺组织中TGF-β、TNF-α和IL-8的释放水平,减少肺组织反复的损伤与修复过程,从而起到减缓气道重构的作用。

[Objective] To investigate the influence of Jianpi Yifei II on inflammatory cytokines and and metalloproteases in lung tissues of rats induced by cigarette smoke combined LPS and to provide theoretical basis to doctors for clinical application. [Methods] The rat model of lung injury was established by using intratracheal injection of LPS combining cigarette smoke. All rats were randomly divided into normal group, model group, Jianpi Yifei II low does group, Jianpi Yifei high does group and prednisone group. General condition of rats was observed and recorded first, then we detected the expression of MMP-9 and TIMP-1 and contents of TGF-β1,TNF-α and IL-8 in lung tissue homogenate or plasma by special assay kits. [Results] After inducing lung injury by treating rats with LPS and cigarette smoke, the general condition of rats in Jianpi Yifei II group and prednisone group was better than in model group. And the ratio of MMP-9/TIMP-1 was lower in the Jianpi Yifei Group and prednisone group than in model group（P〈0.05 or P〈0.01）.In addition, compared to model group, the levels of TNF-α,IL-8 and TGF-β1 in lung tissues or plasma were significantly decreased in Jianpi Yifei II group and prednisone group（P〈0.05 or P 〈0.01）. [Conclusion] Jianpi Yifei II could protect lung tissue from the cigarette smoke and LPS by regulating levels of inflammatory cytokines and MMP-9/TIMP-1 ratio.