摘要
目的:观察扶正化瘀方影响肺组织MMP-2活性与IV型胶原表达的抗肺纤维化作用机制。方法:一次性气管内注射博来霉素诱导肺纤维化模型,分模型对照组、扶正化瘀方组、甲强龙组,每组各14只模型大鼠。另设正常组10只,一次性气管内注射等量生理盐水。造模次日扶正化瘀方组予以4.6 g.kg-1大鼠体重的扶正化瘀方灌胃;甲强龙组予以15 mg.kg-1大鼠体重的甲强龙腹腔注射,正常组和模型组灌喂等量生理盐水;每日1次,共4周。Masson染色观察肺组织胶原沉积,称量肺重量与计算肺系数,Jamall氏法测定肺组织羟脯氨酸含量,明胶酶图法检测肺组织MMP-2与MMP-9的活性,Western blot检测肺组织MMP-2,MMP-9和Ⅳ型胶原的蛋白表达量。结果:与正常组比较,模型组肺系数明显增加,肺组织胶原沉积明显,Hyp含量、Ⅳ型胶原、MMP-2与MMP-9蛋白表达增加,MMP-2活性水平升高,尤其是活性型MMP-2活性升高明显,而MMP-9活性略有下降。与模型组比较,扶正化瘀方与甲强龙均不同程度减轻模型组肺组织胶原沉积与Ⅳ型胶原蛋白表达,减少肺系数与肺组织Hyp含量,降低MMP-蛋白与2活性水平,尤其是活性型MMP-2水平。其中,对肺系数、Ⅳ型胶原蛋白与MMP-2蛋白与活性的抑制作用以扶正化瘀方较为明显。而2种药物对MMP-9蛋白表达与活性无明显影响。结论:扶正化瘀方具有良好的抗大鼠肺纤维化作用,其部分作用机制在于:抑制纤维化肺组织的MMP-2蛋白及其活性,以减少组织的炎性破坏;抑制Ⅳ型胶原过度表达,以减少胶原的病理增生沉积。
Objective： To study the mechanism of Fuzheng Huayu （FZHY） recipe against pulmonary fibrosis relating to MMP- 2 activity and type Ⅳ collagen expression at lung tissue. Method： The pulmonary fibrosis model was induced by intratracheal instillation with bleomycin once in rats. The models were divided into 3 groups： model control, FZHY recipe treated, and methylprednisolone （Solu-Medrol） treated group, each group was of 14 model rats. Normal control group with 10 rats was intoxicated with the same amount of saline. From the second day of intoxication, FZHY recipe treated group orally took FZHY recipe at the dosage of 4. 6 g · kg^- 1 rat wt, methylprednisolone treated group received intraperitoneal injection with 15 mg · kg^- 1 rat wt of methylprednisolone, while model and normal controls took the same volume of saline, 1 time each day and lasting for 4 weeks. Lung and body weights were weighed and the lung/body ratio was calculated. Collagens deposition was check with Masson stain, and lung hydroxyproline （Hyp） content was assayed with Jamall＇ s method. Protein expressions of MMP-2/9 and type IV collagen at lung tissue were analyzed with Western blot and of MMP-2/9 activities by gelatin zymography. Result： Compared to normal rats, the model control rats had a high lung/body ratio, remarkable collagen deposition, increased Hyp content and the expressions of type Ⅳ collagen, MMP-2 and MMP-9 protein at lung tissue, increased MMP-2 activity, in particular active MMP-2 activity, but decreased MMP-9 activity. Compared to model control, FZHY recipe and methylprednisolone obviously attenuated pulmonary collagen deposition, decreased lung/body ratio and Hyp content, downregulated MMP-2 protein expression and activity, in particular active MMP-2 activity, and FZHU recipe had some better actions than methylprednisolone on lung/body ratio, type Ⅳ collagen expression and active MMP-2 activity. But both drug groups had no influence on MMP-9 protein expression and activity. Condusion： FZHY recipe has
出处
《中国中药杂志》
CAS
CSCD
北大核心
2007年第9期835-839,共5页
China Journal of Chinese Materia Medica
基金
上海市科委重点基础项目(04JC14069)
教育部新世纪优秀人才资助计划(NCET-04-0437)
上海市教育委员会E-研究院建设计划(E03008)
上海市重点学科建设项目(Y0302)
