在对关节软骨进行低温保存时，常常缺乏对实验条件和保护剂种类的筛选依据。本论文通过计算不同醇类保护剂的分子结构描述符，利用GFA模型，对筛选后的分子结构描述符建立了关于猪软骨冷冻过程中结晶焓及热应变的QSAR模型。两种模型的R2和Rpre2分别为0.931、0.881和0.845、0.733，均具有良好的拟合性和预测性。通过对模型的分析，发现保护剂分子极性面积越大，脂水分配系数越高，保护剂发挥的保护作用越强；而所添加的保护剂羟基数和碳原子数合适配比时，结晶焓值较小，保护效果更佳；降温速率和保护剂浓度仍然是影响结晶焓和热应变的主要因素。其中，降温速率对结晶焓的影响受到保护剂分子量的制约，而对热应变的影响则存在最佳降温速率（3 ℃/min）。可以看出，保护剂的分子结构是决定低温保护效果的重要因素，利用建立的QSAR模型可以实现对冷冻条件的优化。

There is often a lack of control basis for experimental conditions and cryoprotective agents used during the cryopreservation of articular cartilage. After calculating the diverse molecular descriptors of alcohol-protectants, quantitative structure-activity relationship (QSAR) predictive models based on crystallization enthalpy and thermal strains were built using the genetic function approximation (GFA) method and selected descriptors. The values of R2 and Rpre2 were 0.931, 0.881 and 0.845, 0.733, respectively, sharing a preferably fitting and predictive ability. On analyzing the model, the cooling rate and concentration of the cryoprotectant were confirmed to be the main factors that affected the values of crystallization enthalpy and thermal strain. The degree to which the cooling rate affected the crystallization enthalpy was constrained by the molecular weight. Meanwhile, an optimal cooling rate (3 ℃/min) of the thermal strain was found. In addition, the cryoprotectant shows a stronger protective effect with higher values of molecular polar surface area and AlogP. Moreover, an appropriate proportion of hydroxyl and carbon atoms results in a smaller crystallization enthalpy, indicating an enhanced protective effect. These results suggest that the molecular structure of cryoprotective agents is an important factor determining the effect of cryopreservation. The QSAR model developed in this study can be used for the optimization of freezing conditions.

国家自然科学基金(50906056)；上海市“创新行动计划”国际科技合作项(12430702000)；上海市重点学科项目(T0503，P0502)；上海市自然科学基金(12ZR1420400)；上海市教委科研创新项目(14YZ092)；上海市联盟计划项目。