可降解水凝胶栓塞动脉瘤的实验研究

The study of chitosan/glycerophosphate（C/GP） hydrogel as the embolism material of aneurysms

目的探讨壳聚糖／甘油磷酸钠水凝胶作为动脉瘤栓塞材料的可行性。方法配制2％壳聚糖与56％甘油磷酸钠溶液，不同比例混合，测定混合液pH、37℃成胶时间及力学强度，选择最佳比例。体外栓塞动脉瘤模型，评价导管内操控性；通过兔耳中动脉栓塞评价组织相容性。最终栓塞兔动脉瘤模型。结果当壳聚糖／甘油磷酸钠在7：1时，pH值为7．28，成胶时间为（260±18）S，力学强度可达14kPa。体外动脉瘤模型栓塞见壳聚糖／甘油磷酸钠水凝胶可通过导管在动脉瘤内成胶。兔耳中动脉栓塞后3d，血管周围可见少量炎性细胞浸润，1周时达到高峰，2—3周逐渐消退，4—8周形成肉芽组织，并可见壳聚糖凝胶部分降解。兔动脉瘤栓塞术中见动脉瘤不显影，术后3d病理见动脉瘤被凝胶栓塞，内膜细胞形态正常，动脉壁内未见明显炎性细胞浸润。结论短期观察，壳聚糖／甘油磷酸钠水凝胶可用于动脉瘤栓塞。

Objective To evaluate the feasibility of injectable thermosetting chitosan/ glycerophosphate（C/GP） hydrogel as the embolism material of aneurysms. Method 2% chitosan solution and 56% glycerophosphate solution were mixed in different volume ratios. The pH, colloidization time in 37℃ and mechanic strength of the mixed solution were detected respectively to determine the best ratio. The intracatheter operation of the C/GP hydrogel by embolizing aneurysm models was evaluated. The C/GP hydrogel histocompatibility was evaluated by embolizing rabbit ear arteries. Finally, we embolized rabbit aneurysm models with this C/GP gel. Results When the ratio of C/GP was 7 ： 1 at pH 7. 28, the colloidization time was （260 ± 18 ） seconds and the mechanic strength chould reach 14 kPa. In the experiment of embolizing aneurysm models in vitro, the C/GP gel could arrive in aneurysms through catheter and reach solid state. In the experiment of embolizing rabbit ear arteries, the modest inflammation was observed. This effect peak was found in 1 week, and gradually resolution in 2 - 3 weeks. In 4 - 8 weeks, granulation tissue and slight degradation of C/GP hydrogel could be observed. In the embolism operation of rabbit aneurysms, the aneurysms were disappeared in angiography. In the HE stain slice 3 days after operation, the C/GP hydrogcl in aneurysm caves and normal endomembrane cells were observed. There was no significant flame cell in aneurysm walls. Conclusions In short term view, C/GP hydrogel could be used to embolize aneurysms.