摘要
目的观察己酮可可碱(pentoxifylline,PTX)对博来霉素致肺纤维化大鼠肺组织基质金属蛋白酶2(matrixmetalloproteinase2)和基质金属蛋白酶组织抑制剂1(tissueinhibitorofmatrixmetalloproteinase1)表达的影响,初步探讨其抗肺纤维化的作用机制。方法SD大鼠36只,随机分为模型组、治疗组和对照组。模型组和治疗组气管内注射博来霉素诱导肺纤维化,对照组在相同条件下给予生理盐水。第二天起治疗组大鼠腹腔给予己酮可可碱6mg/kgd,其余两组相同条件下给予生理盐水。治疗的第7d和28d,处死动物取出肺组织,用RTPCR和免疫组化ABC法观察各组鼠肺组织MMP2和TIMP1表达的变化。结果与模型组比较,治疗组经PTX作用的第7d和28d肺组织中MMP2和TIMP1mRNA的基因转录均有减少,MMP2mRNA表达分别降低334%和355%(P<0001),TIMP1mRNA表达分别降低253%和330%(P<005)。免疫组化结果则显示,PTX作用的第7d和28dMMP2分别较模型组降低307%和417%(P<005),TIMP1分别降低131%和198%(P<005)。结论PTX对肺纤维化不同时期肺组织中MMP2和TIMP1的表达均有一定程度的降低作用,其可能通过调整MMP2和TIMP1比值使其趋于平衡,从而延缓甚至抑制纤维化的进程。
? Objective To investigate the effect of pentoxifylline on matrix metalloproteinase 2(MMP 2)and the tissue inhibitor 1 of matrix metalloproteinase(TIMP 1) in rats with pulmonary fibrosis and to study the mechanism.Methods Thirty six Spague Dawley rats were randomly divided into the control group, model group and treatment group. The model group and thetreatment group were induced to produce pulmonary fibrosis with bleomycin endotracheally, while the control group was given with normal saline instead in the same condition. From the second day the rats in the treatment groupwere injected pentoxifylline, endoceliacly with 6mg/kg.d. while the other rats with normal saline instead. On theseventh day and thetwenty eighth day the lungs were isolated. The mRNA expressionof MMP 2 and TIMP 1 was evaluatedby RT PCR quantitative analysis, and the immunohistochemical method was used to investigate the changes of MMP 2 and TIMP 1. Results Compared withthose in the model group, MMP 2 mRNA leveldecreased 33 4% and 35 5%( P <0 001),while TIMP 1mRNAdecreased 25 3% and 33 0%( P <0 05) on the 7th and 28th day, respectively. The immunohistochemical analysis showedthat, compared with those of the model group, the level of MMP 2decreased 30 7% and 41 7%( P <0 05), and TIMP 1decreased 13 1% and 19 8%( P <0 05), respectively. Conclusion PTX can decrease the expression of MMP 2 and TIMP 1 mRNA at different stages of pulmonary fibrosis. It may delay and inhibit the progress of fibrosis by adjusting the ratio of MMP 2 /TIMP 1.〔
出处
《中国组织化学与细胞化学杂志》
CAS
CSCD
2004年第4期440-444,共5页
Chinese Journal of Histochemistry and Cytochemistry
