川芎嗪对哮喘大鼠气道壁胶原沉积和TGF-β1表达的影响

Effect of ligustrazine on the levels of collagen and transforming growth factor-β1 in rats with asthma

摘要:

目的 上皮下胶原沉积及纤维化是哮喘气道重建的典型特征 ,转化生长因子 β1(TGF β1)在此过程中发挥了重要作用。该研究旨在观察川芎嗪对大鼠哮喘模型气道壁胶原及TGF β1含量的影响。 方法 4 0只SD大鼠随机分成对照组 (A)、哮喘组 (B)、激素干预组 (C)、小剂量 (D)和大剂量 (E)川芎嗪干预组 ,以卵蛋白致敏并长期吸入激发制备哮喘模型 ,C ,D ,E组分别在每次激发前腹腔注射地塞米松 0 .5mg 只 ,川芎嗪 4 0mg kg及川芎嗪 80mg kg。 4周后处死大鼠 ,收集肺组织标本观察病理改变 ,并采用免疫组化半定量测定气道壁I ,III型胶原和TGF β1的含量。 结果 B组气道壁III型胶原和TGF β1含量均显著高于A组 ,C ,D ,E组均较B组降低 ,差异有显著性 (均P <0 .0 1) ,E组与A组、C组含量接近 (均P >0 .0 5 ) ,D组III型胶原和TGF β1含量高于E组 ,差异有显著性 (P <0 .0 1) ;气道壁TGF β1表达与III型胶原含量呈显著正相关 (rs =0 .70 6 3,P <0 .0 1)。各组间I型胶原含量差异无显著性 (均P >0 .0 5 )。结论 川芎嗪减少哮喘大鼠气道壁III型胶原沉积和TGF β1的表达 ,对III型胶原的抑制可能部分通过抑制TGF β1的表达而实现。

Abstract:

Objective The formation of subepithelial fibrosis and increased deposition of types I and III collagen are important features of airway remodelling in asthma, while transforming growth factor-β1 (TGF-β1) is the major regulative factor of airway remodelling. The study aims at exploring the effect of ligustrazine on the collagen deposition and the expression of TGF-β1 in the airway wall of asthmatic rats. Methods Forty SD rats were randomly assigned into 5 groups (n=8 each): a normal group (A), an asthma model group (B), a dexamethasone group (C), a low-dose ligustrazine group (D) and a high-dose ligustrazine group (E). The asthma model was established by repeated inhalation of oval bulium. Groups C, D and E were treated by injection of 0.5 mg dexamethason and 40 mg or 80 mg ligustraizine respectively before stimulation, while Group A was treated with normal saline instead. The levels of collagen and TGF-β1 expression in airway wall were semi-quantitatively measured by the immunohisto-chemistry technique. Results The levels of collagen type III and TGF-β1 expression were significantly higher in Group B than those in Group A (P< 0.01). In the Group C, Group D and Group E, the levels of collagen type III and TGF-β1 expression in airway wall were lower than those in Group B (P< 0.01), and there was no difference among Groups E, C and A (P> 0.05). The contents of collagen type I had no difference among all five groups. A close correlation between TGF-β1 expression and collagen type III content in various groups was found (r s= 0.7063, P< 0.01). Conclusions Ligustrazine may reduce the deposition of collagen type Ⅲ and inhibit the expression of TGF-β1.