摘要
53只Wistar大鼠随机分为对照组、慢性阻塞性肺疾病 (COPD)模型组及N 乙酰半胱氨酸 (NAC)组、蛋白激酶C(PKC)抑制剂H7组及转移生长因子 (TGF) β单抗组 ;研究基质金属蛋白酶 (MMPs)及其组织抑制剂 (TIMP 1)在COPD模型气道细胞外基质 (ECM)重塑中的作用及NAC、H7及TGF β单抗等干预因素的影响。结果表明 ,模型组气道壁以Ⅰ型胶原为主的细胞外基质及羟脯氨酸 (Hy)含量、粘膜下成纤维细胞 (Fb)数、MMP 9、2、TIMP 1及TGF βⅠ、Ⅱ受体在支气管肺组织中蛋白和 (或 )mRNA表达较对照组显著增高 ,72kDMMP 2及 92kDMMP 9酶活性亦显著增高 ,NAC组及TGF β单抗组Hy含量及Fb数较模型组显著降低 ,H7组Hy含量则显著增高 ,三个干预组MMP 2、9及TIMP 1和MMP 9、2酶活性表达均较模型组显著减弱 ,三个干预组TGF βⅠ、Ⅱ受体亦有不同程度减弱。MMP 9、2及TIMP 1表达增强表明COPD大鼠模型ECM降解及合成代谢异常活跃 ,与气道ECM重塑密切相关。拮抗氧自由基或TGF β对MMPs、TIMP 1及气道重塑具有调节和减轻作用 ,为探索防治气道细胞外基质重塑的途径提供了一定依据。H7由于具有强抑制胶原酶作用而使胶原沉积增多。
Fifty three Wistar rats were randomly divided into healthy control group, COPD model group and NAC group, PKC inhibitor H7 intervention group and TGF β monocolonal antibody group(TGF β MA group).To study the role of matrix metalloproteinases(MMPs) and the tissue inhibitor of MMPs(TIMP 1) in the airway extracellular matrix(ECM) remodelling of COPD rat models and to observe the effects of NAC, H7 and TGF β MA intervention on the regulation of MMPs and TIMP 1 and on ECM remodelling of the airway walls. Compared with control group, the airway collagen, the hydroxyproline(Hy) content of lung homogenates ,the number of fibroblasts(Fb) , the protein and/or mRNA expressions of MMP 2, MMP 9, TIMP 1 and TGF β Ⅰ, Ⅱ receptor and the enzyme activities of MMP 2 (72kD), MMP 9 (92kD) were significantly increased in COPD model group. In all the drug intervention groups, the expressions of the above parameters were significantly decreased than those in model group except for Hy and Fb in H7 group, protein expression of TGF β I receptor in NAC group and MMP 9 in TGF β MA group. The results suggested that increased MMPs as matrix degrading enzymes might be responsible for the excessive degradation of ECM in airway, whereas incresed TIMPs might promote excessive ECM synthesis and deposition. The imbalance of MMP 9/TIMP 1 was related to the airway ECM remodelling. An antioxidant NAC and TGF β MA might regulate the MMPs/TIMP 1 expression and reduce the airway fibrosis.H7 had strong collagenase inhibitory action,resulting increse in Hy and Fbs. The data may be helpful for searching effective prevention and treatment of airway ECM remodelling.
出处
《解放军医学杂志》
CAS
CSCD
北大核心
2002年第7期593-596,I002,共5页
Medical Journal of Chinese People's Liberation Army
