丹芍化纤胶囊对肺纤维化大鼠MMP-2和TIMP-1表达的影响  

Effect of Danshao Huaxian capsales on the expression of MMP-2 and TIMP-1 in the lung of rats with fibrosis pulmonary

作　　者：何小飞[1] 杨勤[2] 谢汝佳[2] 杨婷[2] 

机构地区：[1]黔南民族医学高等专科学校,贵州都匀558003 [2]贵阳医学院病理生理教研室,贵州贵阳550004

出　　处：《华西药学杂志》2011年第2期127-129,共3页West China Journal of Pharmaceutical Sciences

基　　金：社发攻关项目资助(黔科合SZ字(2008)3049)

摘　　要：目的观察丹芍化纤(DSH)胶囊对博来霉素致肺纤维化大鼠肺组织中基质金属蛋白酶2(MMP-2)和基质金属蛋白酶组织抑制剂1(TIMP-1)表达的影响,并初步探讨其抗肺纤维化的作用机制。方法选取30只SD大鼠,随机分为正常对照组、肺纤维化模型组和丹芍化纤胶囊治疗组。在模型组和治疗组大鼠的气管内注射博来霉素(5 mg·kg-1)诱导肺纤维化,对照组的气管内注射等量生理盐水。次日起,治疗组大鼠ig给予丹芍化纤混悬液(0.8 g·kg-1·d-1),其余两组ig给予等量生理盐水。治疗第28天时处死各组大鼠,计算肺系数,HE染色观察肺组织的病理变化,碱水解法检测肺组织中羟脯氨酸(Hyp)的含量,免疫组化ABC法观察肺组织中MMP-2和TIMP-1表达的变化。结果与对照组比较,模型组大鼠的肺系数明显增加,肺组织中胶原沉积明显,Hyp的含量、MMP-2和TIMP-1蛋白的表达增加。与模型组比较,治疗组大鼠的肺系数明显降低,肺组织中胶原沉积有所减轻,肺组织中Hyp的含量、MMP-2和TIMP-1蛋白的表达减少,但均未恢复正常。结论丹芍化纤具有较好的抗大鼠肺纤维化作用,其作用机制可能部份是通过调节肺组织内MMP-2和TIMP-1比值平衡来延缓甚至抑制纤维化的进程的。OBJECTIVE To investigate the effect of Danshao Huaxian（DSH）capsales on matrix metalloproteinase-2（MMP-2）and the tissue inhibitor-1 of matrix metalloproteinase（TIMP-1）in rats with pulmonary fibrosis and to explore the possible mechanism.METHODS Thirty Spague-Dawley rats were randomly divided into the control group,model group and treatment group.The rats of model group and the treatment group induced pulmonary fibrosis with bleomycin（5 mg·kg-1）endotracheally,while the rats of control group was given normal saline instead.From the second day of injection,the rats in the treatment group were administered intragastricly with DSH（0.8 g·kg-1·d-1）while the other rats were given normal saline instead.All rats were sacrificed on the twenty-eighth day.The lung coefficient were observed.The rat lung histopathology was examined with HE staining.Lung hydroxyproline（Hyp） content was evaluated.The expression of MMP-2 and TIMP-1 were examined by immunohistochemical staining.RESULTS Compared with the control group,the lung coefficient and the Hyp content and expressions of MMP-2 and TIMP-1 were significantly increased,the degree of pulmonary alveoli inflammation and pulmonary fibrosis were detected in the model group.After 4weeks DSH treatment.The lung coefficient were significantly decreased.The degree of pulmonary alveoli inflammation and pulmonary fibrosis was significantly relieved.Hyp content and expression of MMP-2/TIMP-1 were obviously decreased in the treatment group.CONCLUSION DSH has a good action against experimental pulmonary fibrosis which may happen through adjusting the ratio of MMP-2/TIMP-1 to inhibit the progress of the fibrosis.

关 键 词：肺纤维化 丹芍化纤 基质金属蛋白酶 基质金属蛋白酶组织抑制剂 

分 类 号：R96[医药卫生—药理学]