目的：观察芝麻素含药血清对血管紧张素Ⅱ（ Ang Ⅱ）诱导的心肌成纤维细胞增殖及胶原分泌的影响，探讨其可能机制。方法应用血清药理学方法制备大鼠含药血清，采用复合酶消化和差速贴壁法原代培养心肌成纤维细胞，MTT法测定芝麻素对AngⅡ诱导的心肌成纤维细胞增殖的影响， ELISA法测定Ⅰ、Ⅲ型胶原含量与转化生长因子β1（ TGF－β1）水平，比色法测定细胞总抗氧化能力（ T－AOC）及丙二醛（ MDA）含量，Western blot法测定Smad3活化水平。结果芝麻素含药血清可明显抑制AngⅡ诱导的心肌成纤维细胞增殖及胶原分泌（ P＜0.05，P＜0.01），降低TGF－β1含量及Smad3活化水平（P＜0.05，P＜0.01）。此外，芝麻素含药血清可明显提高成纤维细胞抗氧化能力，减少脂质过氧化产物MDA生成（ P＜0.05，P＜0.01）。对照血清对上述各项指标均无明显影响。结论芝麻素含药血清可明显抑制AngⅡ诱导的心肌成纤维细胞增殖与胶原分泌，其机制可能与改善氧化应激状态、调节TGF－β1／Smad信号通路有关。%Objective To investigate the effects of sesamin -containing serum on angiotensin Ⅱ( AngⅡ)-in-duced cardiac fibroblast ( CFB) proliferation and collagen synthesis , and the possible mechanisms .Methods CFBs were separated from neonatal rats with mixed enzyme digestion and purified by differential adhesion methods .After preincuba-tion with sesamin-containing rat serum for 12 hours, CFBs were exposed to Ang Ⅱ(10 -7 mol/L) for 24 hours.CFB pro-liferation was determined by MTT assay .Contents of collagen Ⅰ, collagen Ⅲ and TGF-β1 were determined by enzyme linked immunosorbent assay (ELISA).Levels of total antioxidant capacity (T-AOC) and malonaldehyde (MDA) were evaluated by colorimetric method .Phosphorylation of Smad3 was detected by Western blot analysis .Results Sesamin-containing serum effectively suppressed Ang Ⅱ-induced proliferation and collagen synthesis in CFBs , with significant re-duces in TGF-β1 content and Smad3 phosphorylation (P<0.05 or P<0.01).In addition, preincubation with sesamin -containing serum led to a significant increase of T -AOC and decrease of MDA content in CFBs .Preincubation with control serum had no significant influence on these observations mentioned above .Conclusion Sesamin-containing serum is capable of suppressing Ang Ⅱ-induced CFB proliferation and collagen synthesis , of which the underlying mechanisms might be related to attenuating oxidative stress and regulating TGF -β1/Smad signaling pathway .
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