Evidence-Based Medicine Center, Institute of Integrated Traditional Chinese and Western Medicine, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China Gansu University of Traditional Chinese Medicine, Lanzhou 730000, China Key Laboratory of Evidence Based Medicine and Knowledge Translation of Gansu Province, Lanzhou 730000, China.
Gansu University of Traditional Chinese Medicine, Lanzhou 730000, China.
Acta Biochim Biophys Sin (Shanghai). 2014 Jun;46(6):492-501. doi: 10.1093/abbs/gmu021. Epub 2014 Apr 15.
The main pathological change of radiation-induced heart disease is fibrosis. Emerging evidence has indicated that Astragalus membranaceus and its extractant, Astragalus saponin (AST), were used for treating fibrosis diseases. In the present study, the effects of AST on fibrosis damage induced by irradiation were determined. After being irradiated with 1 or 2-Gy X-rays, obvious changes of endoplasmic reticulum morphology were observed in cardiac fibroblasts (CFs), suggesting that its protein processing function was imbalanced, which indirectly indicated that fibrosis damage was caused by irradiating CFs. The expression levels of TGF-β1 and collagen I (Col-1) were increased at 48-h post-irradiation. Administration of 20 μg/ml AST reduced the production of reactive oxygen species in irradiated CFs and decreased the expression of Col-1, TGF-β1, and p-Smad2/3. Polymerase chain reaction (PCR)-array analysis showed that there were ~30 genes which were mainly classified into extracellular matrix, remodeling enzymes, inflammatory cytokines/chemokines, and TGF-β superfamily, were up-regulated after treatment with 1-Gy X-ray, whereas most of these genes were down-regulated when pretreated with 20 μg/ml of AST. In addition, TIMP1 and Smad7 genes that were down-regulated after treatment with 1-Gy X-ray were up-regulated when pretreated with 20 μg/ml of AST. In conclusion, radiation-induced fibrosis damage was observed at a cellular level. AST attenuated this fibrosis damage effect in irradiated CFs and this anti-fibrosis effect may be closely related to its antioxidant action. The involvement of fibrosis-related molecules in irradiated CFs was systematically demonstrated by a PCR array for the first time. AST reversed the expression of the majority of genes changed by irradiation, which further confirmed its anti-fibrosis effect.
辐射性心脏病的主要病变是纤维化。新出现的证据表明，黄芪及其提取物黄芪皂苷（AST）已被用于治疗纤维化疾病。在本研究中，测定了 AST 对辐射诱导的纤维化损伤的影响。用 1 或 2 Gy X 射线照射后，心肌成纤维细胞（CFs）的内质网形态发生明显变化，提示其蛋白质加工功能失衡，间接表明 CFs 受到照射会导致纤维化损伤。照射后 48 h，TGF-β1 和胶原 I（Col-1）的表达水平增加。给予 20 μg/ml AST 可减少辐照 CFs 中活性氧的产生，并降低 Col-1、TGF-β1 和 p-Smad2/3 的表达。聚合酶链反应（PCR）-array 分析显示，有约 30 个基因主要分类为细胞外基质、重塑酶、炎症细胞因子/趋化因子和 TGF-β 超家族，用 1 Gy X 射线处理后这些基因表达上调，而用 20 μg/ml AST 预处理时，这些基因中的大多数表达下调。此外，用 1 Gy X 射线处理后下调的 TIMP1 和 Smad7 基因在用 20 μg/ml AST 预处理时上调。总之，在细胞水平观察到辐射诱导的纤维化损伤。AST 减弱了辐照 CFs 中的这种纤维化损伤作用，这种抗纤维化作用可能与其抗氧化作用密切相关。首次通过 PCR 阵列系统地证明了辐照 CFs 中纤维化相关分子的参与。AST 逆转了大多数被照射改变的基因的表达，进一步证实了其抗纤维化作用。
