补阳还五汤对特发性肺纤维化模型大鼠肺组织内皮间质转化的影响及其机制研究
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篇名: 补阳还五汤对特发性肺纤维化模型大鼠肺组织内皮间质转化的影响及其机制研究
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摘要: 目的:探讨补阳还五汤对特发性肺纤维化(IPF)模型大鼠肺组织内皮间质转化(EndMT)的影响,并探讨其可能机制。方法:将雄性SD大鼠随机分为正常组、模型组、地塞米松组[0.405 mg/(kg·d)]和补阳还五汤低、中、高剂量组[6.435、12.87、25.74 g/(kg·d),以生药总质量计],每组8只。除正常组外,其余各组大鼠均于气管内注射博来霉素以复制IPF模型。自造模后第2天起,正常组和模型组大鼠均灌胃水[10 mL/(kg·d)],各给药组大鼠灌胃相应药物,每日1次,连续28 d。末次给药24 h后,采用免疫组化法检测大鼠肺组织中内皮细胞标志物[血小板内皮细胞黏附分子1、血管内皮细胞钙黏蛋白]和间质细胞标志物[α-平滑肌肌动蛋白、成纤维细胞特异性蛋白1]的表达情况,采用蛋白质印迹法检测大鼠肺组织中Notch4、DLL4的表达情况。结果:与正常组比较,模型组大鼠肺组织中内皮细胞标志物的表达水平均显著降低,间质细胞标志物以及Notch4、DLL4的表达水平均显著升高(P<0.01)。各给药组大鼠肺组织中内皮细胞标志物的表达水平均显著高于模型组,补阳还五汤低剂量组上述指标显著低于地塞米松组;间质细胞标志物以及Notch4、DLL4的表达水平均显著低于模型组,补阳还五汤低剂量组上述指标显著高于地塞米松组(P<0.05或P<0.01)。结论:补阳还五汤可通过干预EndMT来减轻大鼠的IPF,其机制可能与抑制DLL4/Notch4信号通路有关。
ABSTRACT: OBJECTIVE: To investigate the effects of Buyang huanwu decoction on endothelial-mesenchymal transformation (EndMT) of lung tissue in idiopathic pulmonary fibrosis (IPF) model rats, and to explore its potential mechanism. METHODS: Male SD rats were randomly divided into normal group, model gorup, dexamethasone group [0.405 mg/(kg·d)], Buyang huanwu decoction low-dose, medium-dose and high-dose groups [6.435, 12.87, 25.74 g/(kg·d), by raw material], with 8 rats in each group. Except for normal group, other groups were given endotracheal injection of bleomycin to induce IPF model. On the second day after modeling, normal group and model group were given water intrgastrically [10 mL/(kg·d)]; administration groups were given relevant medicine intragastrically, once a day, for consecutive 28 days. 24 h after last medication, the expression of endothelial cell markers [platelet endothelial cell adhesion molecule 1, vascular endothelial cell cadherin] and interstitial cell markers [α-smooth muscle actin, fibroblast specific protein 1] were detected by immunohistochemistry method. The expression of Notch4 and DLL4 in lung tissue of rats were detected by Western blotting assay. RESULTS: Compared with normal group, the expression of endothelial cell markers were decreased significantly in lung tissue of model group, while the expressipon of interstitial cell markers, Notch4 and DLL4 were increased significantly (P<0.01). Compared with model group, the expression of endothelial cell markers in lung tissue of rats were increased significantly in administration groups, while Buyang huanwu decoction low-dose group was significantly lower than dexamethasone group; the expression of interstitial cell markers, Notch4 and DLL4 were decreased significantly, while Buyang huanwu decoction low-dose group was significantly higher than dexamethasone group (P<0.05 or P<0.01). CONCLUSIONS: Buyang huanwu decoction can relieve IPF of model rats by intervening in EndMT, the mechanism of which may be associated with inhibiting DLL4/Notch4 singaling pathway.
期刊: 2019年第30卷第20期
作者: 杨邯捷,赵惠亮,渠景连,谭芸,王俊霞
AUTHORS: YANG Hanjie,ZHAO Huiliang,QU Jinglian,TAN Yun,WANG Junxia
关键字: 特发性肺纤维化;补阳还五汤;内皮间质转化;内皮细胞标志物;间质细胞标志物;DLL4/Notch4信号通路;机制;大鼠
KEYWORDS: Idiopathic pulmonary fibrosis; Buyang huanwu decoction; Endothelial-mesenchymal transformation; Endothelial cell marker; Interstitial cell marker; DLL4/Notch4 singaling pathway; Mechanism; Rats
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