大黄酸通过抑制miR-21而干预TGF-β1/Smad通路并减轻博莱霉素所致大鼠肺纤维化  

Rhein attenuates bleomycin-induced rats pulmonary fibrosis through TGF-β1/Smad pathway by inhibiting miR-21 expression

作　　者：屈艳[1] 张崇[2] 贾岩龙[2] 宋宇[2] 牛秉轩[2] 詹合琴[2] 

机构地区：[1]新乡医学院基础医学院,河南新乡453003 [2]新乡医学院药学院,河南新乡453003

出　　处：《中国病理生理杂志》2017年第1期149-153,共5页Chinese Journal of Pathophysiology

基　　金：河南省科技公关项目(No.122102310200);新乡市经济社会发展重点科研项目(No.S10008);新乡医学院第七批省级重点学科开放课题(No.ZD200903);新乡医学院培育基金资助项目(No.2014QN130)

摘　　要：目的:观察大黄酸(rhein,RH)对博莱霉素所致肺纤维化大鼠微小RNA-21(miR-21)表达以及转化生长因子β1(TGF-β1)/Smad通路的影响。方法:博莱霉素一次性气管内注射复制大鼠肺纤维化模型,随机分为RH低、中、高剂量组及模型(model)组;正常对照组大鼠气管内注射生理盐水。用药28 d后,HE染色观察各组大鼠肺组织形态学的变化;测定肺系数、肺组织羟脯氨酸含量;real-time PCR检测肺组织中miR-21和TGF-β1/Smad7m RNA表达;Western blot法分析TGF-β1和Smad7蛋白的表达。结果:与model组相比,RH用药组大鼠的肺泡炎及肺纤维化程度有明显降低,肺系数及肺组织羟脯氨酸含量也显著减少,肺组织中miR-21表达下降,TGF-β1的m RNA和蛋白表达水平也明显下降,Smad7的mRNA及蛋白表达水平明显增高(P<0.05)。结论:RH抗肺纤维化的作用可能与抑制miR-21的表达,从而干预TGF-β1/Smad信号通路,减少细胞外基质沉积有关。AIM：To investigate the effect of rhein on bleomycin-induced pulmonary fibrosis and the expression of micro RNA-21（miR-21）and transforming growth factor-β1（TGF-β1）/Smad signaling molecules in rats. METHODS：A single dose of bleomycin was intratracheal injected into the SD rats to induce pulmonary fibrosis. After injection of bleomycin,the rats were randomly divided into low-,medium- and high-dose rhein treatment groups and model group. The rats that were instilled with normal saline intratracheally served as control group. After the treatment for 28 d,the pulmonary pathologic changes were observed under microscope with hematoxylin-eosin staining. The lung coefficient and hydroxyproline content were also measured. The expression of miR-21 and the m RNA levels of TGF-β1 and Smad7 in the lung tissues were detected by real-time PCR. The protein levels of TGF-β1 and Smad7 were determined by Western blot. RESULTS：Rhein significantly attenuated the experimental alveolitis,pulmonary fibrosis,lung coefficient and hydroxyproline contents in the rats. Rhein obviously decreased the expression of miR-21,and the m RNA and protein levels of TGF-β1,but significantly increased the m RNA and protein levels of Smad7 in the lung tissues. CONCLUSION：Rhein effectively prevents bleomycin-induced pulmonary fibrosis by inhibiting the expression of miR-21 and promoting the expression of Smad7,thus regulating the TGF/Smad signaling pathway to decrease extracellular matrix deposition.

关 键 词：大黄酸 肺纤维化 微小RNA-21 转化生长因子β1 SMAD7 

分 类 号：R363.2[医药卫生—病理学]