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S-烯丙基半胱氨酸对博来霉素诱导的大鼠肺纤维化的减轻作用

Attenuation of Bleomycin-Induced Pulmonary Fibrosis in Rats with S-Allyl Cysteine.

作者信息

Tsukioka Takuma, Takemura Shigekazu, Minamiyama Yukiko, Mizuguchi Shinjiro, Toda Michihito, Okada Shigeru

机构信息

Department of Thoracic Surgery, Osaka City University Graduate School of Medicine, Osaka 5458585, Japan.

Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, Osaka 5458585, Japan.

出版信息

Molecules. 2017 Mar 29;22(4):543. doi: 10.3390/molecules22040543.

Abstract

Pulmonary fibrosis is a complex disease with high mortality and morbidity. As there are currently no effective treatments, development of new strategies is essential for improving therapeutic outcomes. -allyl cysteine (SAC) is a constituent of aged garlic extract that has demonstrated efficacy as an antioxidant and anti-inflammatory agent. The current study examines the effects of SAC on pulmonary fibrosis induced by a single intratracheal instillation of bleomycin (2.5 mg/kg). SAC was administered to rats as 0.15% SAC-containing diet from seven days prior to instillation up until the conclusion of the experiment (14 days post-instillation). SAC significantly reduced collagen mRNA expression and protein deposition (33.3 ± 2.7 μg/mg and 28.2 ± 2.1 μg/mg tissue in vehicle- and SAC-treated rats, respectively), and decreased fibrotic area, as assessed histologically. In the rats' lungs, SAC also attenuated the increased expression of transforming growth factor-β1 (TGF-β1), a central regulator of myofibroblast recruitment, activation, and differentiation. While bleomycin instillation increased the number of myofibroblasts within the lung mesenchymal area, this change was significantly reduced by SAC treatment. SAC may exert efficacy as an anti-fibrotic by attenuating myofibroblast differentiation through TGF-β1-mediated fibroproliferative processes. Thus, our results indicate SAC may be useful for the prevention or treatment of pulmonary fibrosis.

摘要

肺纤维化是一种死亡率和发病率都很高的复杂疾病。由于目前尚无有效的治疗方法,因此开发新的治疗策略对于改善治疗效果至关重要。S-烯丙基半胱氨酸(SAC)是 aged garlic extract 的一种成分,已证明具有抗氧化剂和抗炎剂的功效。本研究考察了 SAC 对单次气管内滴注博来霉素(2.5mg/kg)诱导的肺纤维化的影响。从滴注前 7 天至实验结束(滴注后 14 天),给大鼠喂食含 0.15%SAC 的饮食。SAC 显著降低了胶原蛋白 mRNA 表达和蛋白质沉积(分别为溶剂处理组和 SAC 处理组大鼠组织中的 33.3±2.7μg/mg 和 28.2±2.1μg/mg),并减少了纤维化面积,这是通过组织学评估得出的。在大鼠肺中,SAC 还减弱了转化生长因子-β1(TGF-β1)表达的增加,TGF-β1 是肌成纤维细胞募集、激活和分化的关键调节因子。虽然博来霉素滴注增加了肺间质区域内肌成纤维细胞的数量,但 SAC 处理显著减少了这种变化。SAC 可能通过减弱 TGF-β1 介导的纤维增殖过程中的肌成纤维细胞分化而发挥抗纤维化功效。因此,我们的结果表明 SAC 可能对预防或治疗肺纤维化有用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0556/6154609/92c855406c9e/molecules-22-00543-g001.jpg

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