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不同剂量丹参联合川芎嗪对肺纤维化大鼠的保护作用
徐博,王甜,李毅,郭伟,姬新才
0
(陕西省人民医院急诊内科)
摘要:
【摘要】目的 探讨不同剂量丹参与川芎嗪联合对肺纤维化大鼠的保护作用及机制。方法 选取180只健康雄性大白鼠作为研究对象,按其治疗方法将其分为A组、B组、C组、D组、E组和F组,每组30只,A组大鼠予以09%氯化钠溶液进行气管灌注,其余5组大鼠均予以博莱霉素气管灌注建立肺纤维化模型。模型建立成功后A组和B组每日予以09%氯化钠溶液治疗,C组予地塞米松治疗,D组予以丹参与川芎嗪联合小剂量治疗,E组予以丹参与川芎嗪联合中剂量治疗,F组予以丹参与川芎嗪联合大剂量治疗。治疗后比较不同时间点内各组大鼠间血清转化生长因子β-1( TGF-β1)、肺组织结缔组织生长因子(CTGF)、碱性成纤维细胞生长因子(bFGF)、肺组织羟脯氨酸 (HYP)、肺组织蛋白络氨酸激酶(JAK1)、信号转导与转录活化因子1(STAT1)、Ⅰ型胶原(ColⅠ)和Ⅲ型胶原(ColⅢ)mRNA 、细胞间粘附因子-1(ICAM-1)、血清肿瘤坏死因子α(TNF-α) 、白介素(IL)-6、IL-17的表达水平及丙二醛(MDA) 、超氧化物歧化酶 (SOD)含量和肺泡炎症程度及肺纤维化程度。结果 较B组而言,C、D、E及F组大鼠TGF-β1、TNF-α、CTGF、bFGF、JAK1、STAT1及ICAM1含量在治疗第7天、14天和28天时均少于A组,且E组和F组减少程度均大于B组和D组,B组和D组及E组和F组间比较差异无统计学意义(P>0.05)。较B组而言,C、D、E及F组大鼠其IL-6、IL-17、HYP、MDA、SOD、ColⅠmRNA和ColⅢmRNA 含量在治疗第7d、14d和28d时均较A组增多或减少,且E组和F组增加或减少程度均大于B组和D组,B组和D组及E组和F组间比较差异无统计学意义(P<0.05)。较B组而言,C、D、E及F组大鼠其肺泡炎症程度和肺纤维化程度评分在治疗第7天、14天和28天时均较A组低,E组和F组降低程度均大于B组和D组,B组和D组及E组和F组间比较无统计学意义,且随着时间的延长,肺泡炎症和肺纤维化程度逐渐降低(P<0.05)。结论 不同剂量丹参联合川芎嗪对肺纤维化大鼠的肺部组织有着一定的保护作用,其主要机制可能为丹参联合川芎嗪可一定程度上抑制肺组织中TGF-β1、TNF-α、ColⅠmRNA及ColⅢmRNA等细胞因子的表达有关。
关键词:  丹参  川芎嗪  肺纤维化大鼠  保护作用  作用机制
DOI:
基金项目:陕西省自然科学基础研究项目(2014JM4157)
Protective effect and mechanism of different doses of Salvia miltiorrhiza combined with ligustrazine on pulmonary fibrosis in rats
XU Bo,WANG Tian,LI Yi,GUO Wei,JI Xincai
(Department of Emergency Internal Medicine)
Abstract:
【Abstract】Objective To investigate the protective effect and mechanism of Salvia miltiorrhiza (SM) combined with ligustrazine on pulmonary fibrosis in rats. Methods 180 healthy male rats were selected as subjects and randomly divided into group A, group B, group C, group D, group E and group F, according to their treatment. Each group of rats were treated with 0.9% sodium chloride solution for tracheal perfusion, and the other four groups were treated with bleomycin tracheal perfusion to establish pulmonary fibrosis model. After that, the rats in group A and group B were treated with 0.9% sodium chloride solution daily. Group C was treated with dexamethasone. Group D was treated with salvia miltiorrhiza and ligustrazine combined with low dose. Group E was treated with salvia miltiorrhiza combined with ligustrazine. Group F was treated with salvia miltiorrhiza combined with high dose of ligustrazine. The expression levels of serum transforming growth factor beta 1 (TGFbeta 1), lung tissue, connective tissue growth factor (CTGF), basic fibroblast growth factor (bFGF), hydroxyproline (HYP), protein tyrosine kinase in lung tissue(JAK1), signal transducer and activator of transcription 1 (STAT1), 1 collagen (Col I) and collagen type III (Col III) mRNA, intercellular adhesion molecule-1 (ICAM-1), serum tumor necrosis factor alpha (TNFalpha), interleukin (IL)-6, IL-17 among 4 groups of rats were compared between different time points after treatment. Results The levels of TGFβ1, TNF-α, CTGF, bFGF, JAK1, STAT1 and ICAM1 in group C, D, E and F were significantly higher than those in group B at the 7th, 14th and 28th day of treatment. No significant difference was detected between group B and group D, group E and group F (P<0.05).The levels of IL-6, IL-17, HYP, MDA, SOD, ColⅠmRNA and ColⅢmRNA in group C, D, E and F were increased or decreased than group A compared with group B at the 7th, 14th and 28th day of treatment. The increasing or decreasing level of group E and group F was greater than that of group B and group D. No significant difference was detected between group B and group D, group E and group F (P<0.05). The levels of alveolar inflammation and pulmonary fibrosis in C, D, E and F groups were lower than those in group A compared with group B at the 7th, 14th and 28th day of treatment. The decreasing level of group E and group F was higher than that of group B and group D. No significant difference was detected between group B and group D, group E and group F, and the level of alveolar inflammation and pulmonary fibrosis decreased gradually with the prolongation of time (P<0.05). Conclusion Different doses of danshen combined with ligustrazine has a protective effect on rat pulmonary fibrosis of the lung tissue and the main mechanism for Salvia Ligustrazine can inhibit lung TGF beta 1, TNFalpha, a closed expression of Col 1 mRNA and Col of mRNA and other cytokines.
Key words:  Salvia miltiorrhiza  Ligustrazine  Pulmonary fibrosis  Protective effect  Mechanism of action

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