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γ射线辐照后细胞外组织基质降解与不稳定性的量热研究

Calorimetric study of extracellular tissue matrix degradation and instability after gamma irradiation.

作者信息

Sun Wendell Q, Leung Patrick

机构信息

LifeCell Corporation, One Millennium Way, Branchburg, NJ 08876, USA.

出版信息

Acta Biomater. 2008 Jul;4(4):817-26. doi: 10.1016/j.actbio.2008.02.006. Epub 2008 Mar 3.

Abstract

Native extracellular tissue matrix (ECM) is increasingly used for tissue repair and regeneration. The kinetics of gamma irradiation damage on human dermis ECM was studied by differential scanning calorimetry (DSC). Dermis ECM was irradiated at a low-dose rate of 0.23 kGy h(-1) in order to study the progression of ECM damage as the gamma dose increased from 0 to 32 kGy. The study showed that the effect of gamma irradiation above 2 kGy was predominantly peptide chain scission. As the gamma dose increased, the stability of irradiated ECM decreased further, and multiple ECM domains of different stability were detected. Even a moderate gamma dose (7-12 kGy) could decrease the onset denaturation temperature of ECM to below body temperature. DSC analysis also showed partial and spontaneous protein denaturation in gamma-irradiated, rehydrated ECM at 37 degrees C. In vitro rehydration tests confirmed that a significant fraction of the irradiated ECM disintegrated into minute ECM fragments at 37 degrees C, although the irradiated ECM appeared to be normal at 4 degrees C and room temperature. DSC data were correlated well to effects of gamma irradiation on ECM microstructure, mechanical property and in vitro cell response reported earlier by us. A model was presented to describe the kinetics of gamma-irradiation-induced alterations of tissue ECM properties.

摘要

天然细胞外组织基质(ECM)越来越多地用于组织修复和再生。通过差示扫描量热法(DSC)研究了γ射线辐照对人真皮ECM的损伤动力学。为了研究随着γ剂量从0增加到32 kGy时ECM损伤的进展情况,以0.23 kGy h(-1)的低剂量率对真皮ECM进行辐照。研究表明,2 kGy以上的γ射线辐照效应主要是肽链断裂。随着γ剂量的增加,辐照后ECM的稳定性进一步降低,并且检测到了不同稳定性的多个ECM结构域。即使是中等剂量的γ射线(7 - 12 kGy)也会使ECM的起始变性温度降至体温以下。DSC分析还表明,在37℃下,γ射线辐照并复水的ECM中存在部分自发的蛋白质变性。体外复水试验证实,尽管辐照后的ECM在4℃和室温下看起来正常,但在37℃时,相当一部分辐照后的ECM会分解成微小的ECM片段。DSC数据与我们之前报道的γ射线辐照对ECM微观结构、力学性能和体外细胞反应的影响密切相关。提出了一个模型来描述γ射线辐照引起的组织ECM性质变化的动力学。

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