摘要
目的:观察转化生长因子-β1(TGF-β1)、巨噬细胞在心肌梗死后心肌纤维化发生发展过程中的变化及当归的治疗作用,探讨心肌梗死后心肌纤维化的发生及当归的干预机制。方法:结扎SD大鼠冠脉前降支复制心肌梗死模型,随机分为假手术(sham)组、心肌梗死(M I)组和心肌梗死当归(M I+angelica)组。术后24 h开始给药,M I+angelica组腹腔注射当归(20 mL.kg-1.d-1,相当于生药10 g.kg-1.d-1),sham组和M I组腹腔注射等量生理盐水。于术后1、2、4周记录左室血流动力学改变,检测非梗死区心肌胶原含量、TGF-β1及巨噬细胞的变化。结果:①M I组和M I+angelica组非梗死区心肌TGF-β1及巨噬细胞阳性表达显著高于sham组(P<0.01),以1周的阳性表达为最高,但M I+angelica组低于M I组(P<0.01);②术后各时点M I组心功能受损,于术后2周和4周心肌胶原含量明显高于sham组(P<0.01);术后4周M I+angelica组心功能损害轻于M I组,心肌胶原含量低于M I组(P<0.01)。结论:当归通过抑制巨噬细胞在非梗死区的浸润、下调TGF-β1的表达,阻断促纤维化发生的环节,减轻心肌梗死后非梗死区反应性胶原的过度沉积,防治心肌梗死后心肌纤维化,改善心脏功能。
AIM: To investigate 1 ) the role of transforming growth factor -β1 ( TGF -β1 ) and macrophage infiltration during the development of myocardial fibrosis (MF) in rats after myocardial infarction (MI) ; and 2) mechanisms of MF post- MI and the inhibitory effect of angelica. METHODS: Sprague- Dawley (SD) rats were subjected to MI by ligaing the left anterior descending coronary artery. The animals were randomly divided into three groups: sham, MI and MI + angelica. After 24 hours of ligation, rats received angelica (20 mL · kg^-1 · d^-1 , ip) or saline. Left ventricular hemodynamics were measured and rats were killed at week 1, week 2 and week 4, respectively. Collagen content, macrophage infiltration and TGF -β1 expression were examined in the non - infarcted area. RESULTS: ① In MI group, the numbers of macrophage and TGF -β1 expression were significantly upregulated compared to sham at week 1 post - MI and remained elevated at week 4 ( P 〈 0. 01 ). Angelica significantly decreased macrophage infiltration and TGF -β1 expression ( P 〈 0.01 vs MI). ② Collagen content was increased significantly in MI group compared to sham at week 2 and week 4 ( P 〈0. 01 ), and decreased in MI + angelica group (P 〈 0. 05 vs MI). ③ Cardiac function was markedly decreased post - MI in MI group ( P 〈 0. 01 ), and improved at week 4 in MI + angelica group ( P 〈 0. 05). CONCLUSION : In MF post - MI, angelica may have an antifibrotic effect by decreasing macrophage infiltration and TGF -β1 expression, by which reactive myocardial fibrosis is reduced, and cardiac function is improved.
出处
《中国病理生理杂志》
CAS
CSCD
北大核心
2006年第10期1965-1969,共5页
Chinese Journal of Pathophysiology
关键词
当归
心肌梗死
巨噬细胞
转化生长因子Β
Angelica sinensis
Myocardial infarction
Maerophages
Transforming growth factor beta