| 杨礼腾,刘欣,程德云,方洵,穆茂.迷迭香二萜芬提取物对肺纤维化大鼠肺组织TGF-β1及其信号通路分子mRNA表达的影响[J].中国中西医结合杂志,2013,33(6):0819-0824 |
| 迷迭香二萜芬提取物对肺纤维化大鼠肺组织TGF-β1及其信号通路分子mRNA表达的影响 |
| Effects of Diterpene Phenol Extract of Rosmarinus Officinalis on TGFβ1 and mRNA Expressions of Its Signaling Pathway Molecules in the Lung Tissue of Pulmonary Fibrosis Rats |
| 免费下载全文 查看/发表评论 下载PDF阅读器 |
| |
| DOI：10.7661/CJIM.2013.06.0819 |
| 中文关键词: 肺纤维化 转化生长因子beta1 迷迭香 胶原 |
| 英文关键词:pulmonary fibrosis transforming growth factor-beta1 Rosmarinus Officinalis collagen |
| 基金项目: |
|
| 摘要点击次数: 2165 |
| 全文下载次数: 1848 |
| 中文摘要: |
| 目的探讨迷迭香二萜芬提取物（diterpene phenol extract of Rosmarinus Officinalis， DERO）调控肺纤维化肺胶原代谢失衡的作用机制。方法50只健康SD大鼠，随机分为生理盐水组（NS组）、博莱霉素肺损伤组（BLM组）及DERO低、中、高剂量［50、100、200 mg/（kg·d）］组（分别简称为DERO1、2、3组），每组10只，通过博莱霉素一次性气管内滴入复制肺纤维化大鼠模型，并在肺损伤修复过程中予DERO灌胃干预，于第29天早上取大鼠肺组织，运用组织芯片，进行HE、胶原纤维染色及免疫组化、原位杂交，分别检测肺组织有核细胞数、胶原蛋白、Ⅰ型胶原（type Ⅰ collagen，Collagen-Ⅰ）和转化生长因子βⅡ型受体（transforming growth factor-beta typeⅡ receptor，TGFβRⅡ）、Smad4 mRNA的表达，应用实时荧光定量RT-PCR技术检测转化生长因子beta1（transforming growth factor-beta1，TGF-β1）mRNA的表达。结果与NS组比较，BLM组肺组织胶原沉积明显，炎症浸润程度较重（P<0.05，P<0.01），DERO1组与BLM组比较，两项指标差异无统计学意义（P>0.05），DERO2及DERO3组肺组织胶原沉积及炎症浸润程度皆明显减轻（P<0.05， P<0.01）；与NS组比较，BLM组肺组织Collagen-Ⅰ、TGF-β1 RⅡ、Smad4 mRNA及TGF-β1 mRNA表达明显上调（P<0.05，P<0.01），与BLM组比较，DERO1组4项指标变化不明显（P>0.05），而DERO2及DERO3组，Collagen-Ⅰ、TGF-β1 RⅡ及TGF-β1 mRNA表达皆有明显下调（P<0.05，P<0.01），但两组Smad4 mRNA下调不明显（P>0.05），与DERO1组比较，DERO2及DERO3组除Smad4 mRNA外，余3项指标皆低于DERO1组（P<0.05），而DERO2组与DERO3 组比较，4项指标差异无统计学意义（P>0.05）。结论DERO在肺纤维化胶原代谢失衡中具有调控作用，能抑制胶原纤维的过度沉积，尤其是Collagen-Ⅰ的过度沉积，其作用机制可能主要是通过抑制TGF-β1、TGFβRⅡmRNA表达的上调，从而干扰TGF-β-Smad信号通路对靶基因尤其是Ⅰ型前胶原靶基因的激活而实现的。 |
| 英文摘要: |
| ObjectiveTo investigate the regulative mechanism of the diterpene phenol extract of Rosmarinus Officinalis （DERO）on the imbalance of collagen metabolism of the lung tissue in pulmonary fibrosis rats. MethodsFifty healthy Sprague-Dawley rats were randomly divided into the normal saline group （NS）， the bleomycin-induced lung injury group （BLM）， the low dose DERO group （at the daily dose of 50 mg/kg）， the moderate dose DERO group （at the daily dose of 100 mg/kg）， and the high dose DERO group （at the daily dose of 200 mg/kg）， 10 in each group （abbreviated as DERO 1， 2， 3， respectively）. The pulmonary fibrosis rat model was prepared by disposable intratracheal instillation of bleomycin. DERO was administered by gastrogavage as intervention during the repairing process of lung injury. On the morning of the 29th day， the rats′ lung tissue was extracted. The karyocyte number， collagen protein， type Ⅰ collagen （collagen Ⅰ） and transforming growth factor-beta type Ⅱ receptor（TGFβRⅡ）， Smad4 mRNA expressions were semi-quantitatively determined using tissue microarray， HE staining， collagen fiber dyeing， immunohistochemical assay， and in situ hybridization. Using real-time fluorescent quantification RT-PCR， the mRNA expression of transforming growth factor-beta1 （TGF-β1） were detected. ResultsCompared with the NS group， the collagen deposition of the lung tissue was obvious and the inflammatory infiltration was more severe in the BLM group （P<0.05， P<0.01）. There was no statistical difference in the aforesaid 4 indices between the DERO1 group and the BLM group （P>0.05）. The collagen deposition and the inflammatory infiltration were obviously alleviated in the DERO2 and DERO3 groups （P<0.05， P<0.01）. Compared with the NS group， the mRNA expressions of collagen-Ⅰ， TGF-β1 RⅡ， Smad4， and TGF-β1 were obviously up-regulated in the BLM group （P<0.05， P<0.01）. Compared with the BLM group， the aforesaid four indices were not statistically changed in the DERO1 group （P>0.05）. But the mRNA expressions of collagen-Ⅰ， TGF-β1 RⅡ， Smad4， and TGF-β1 were obviously down-regulated in the DERO2 and DERO3 groups （P<0.05， P<0.01）. But the down-regulation of Smad4 expression was not obvious in the DERO2 and the DERO3 groups （P>0.05）. Compared with the DERO1 group， the mRNA expressions of collagen-Ⅰ， TGF-β1 RⅡ， TGFβ1 were all obviously lower in the DERO2 and the DERO3 groups （P<0.05）. But there was no statistical difference in the aforesaid 4 indices between the DERO2 group and the DERO3 group （P>0.05）. ConclusionsDERO could regulate imbalanced collagen metabolism of pulmonary fibrosis. It could inhibit excessive deposition of collagen fibers， especially excessive deposition of collagen-Ⅰ. Its mechanisms might be realized by inhibiting up-regulation of TGF-β1 and TGFβRⅡ mRNA expressions， thus interfering the activation of TGF-β-Smad signaling pathway on target genes， especially on type Ⅰ precollagen target gene. |
| 关闭 |
扫描微信二维码，获取更多信息