辛伐他汀凝胶盖髓剂初步研究Ⅰ

Chitosan-glycerophosphae gel loaded with simvastatin used as pulp capping material in the molar of rats

目的:制备辛伐他汀温敏性凝胶缓释系统,初步探索辛伐他汀促进牙髓修复的作用。方法:制备辛伐他汀壳聚糖温敏性缓释凝胶,紫外分光光度法检测缓释效果并绘制释放曲线。大鼠磨牙行活髓切断术,分别以载有辛伐他汀的壳聚糖缓释凝胶(简称辛伐他汀缓释凝胶)、壳聚糖/甘油磷酸钠凝胶(简称空白凝胶)、氢氧化钙盖髓,并设对侧为空白对照组,术后1、3、7、14、28 d处死,拍摄X线片,HE染色观察牙髓情况。结果:37℃下,空白凝胶15 min内凝固,辛伐他汀缓释凝胶8 min内凝固。48 h辛伐他汀快速释放,60 d后达到溶质梯度平衡,凝胶内的辛伐他汀持续平稳释放,累计释放率为61.5%。活髓切断术后,氢氧化钙组28 d受试牙根管口见高密度钙化屏障,辛伐他汀缓释凝胶组术后7、14、28 d的根管口见高密度钙化屏障,空白凝胶组未见高密度影像。HE染色结果显示,辛伐他汀组术后7 d盖髓断面牙髓结构正常,成牙本质样细胞向断面聚集并形成早期钙化团块,28 d形成早期钙化桥;氢氧化钙组术后7 d表现为盖髓剂下方断面和髓腔内牙髓组织凝固性坏死现象,失去正常结构,与周围组织界限明显。结论:辛伐他汀缓释凝胶缓释性能良好。作为盖髓剂,其组织相容性好,有促进修复性牙本质形成的潜能。

Objective： Simvastatin chitosan-glycerophosphae gel,was used for sustained release of simvastatin,and an experimental model of pulpotomy in rats was established,so as to explore the role of simvastatin after dental pulp injure. Methods： Chitosan-glycerophosphae gel and chitosan thermosensitive hydrogel loaded with simvastatin into the gel was prepared. The controlled release of simvastatin,as measured by UV spectrophotometry,was monitored for 60 days. Pulpotomy in rat maxillary first molars,using simvastatin chitosan gel（ S-C-GP）,chitosan gel（ C-GP）,and calcium hydroxide as direct pulp capping materials,and the contralateral teeth were used as controls. 1,3,7,14 and 28 days after the operation,animals were sacrificed. X-ray observation was carried out in 30 minutes,then slicements were HE stained after EDTA decalcified. Results： Chitosan thermosensitive hydrogel solidified within 15 minutes at 37 ℃,and simvastatin chitosan thermosensitive hydrogel solidified within 8 minutes at 37 ℃. During monitoring of the controlled release,after a short and fast 48 h release,a stable release process could be observed no less than 60 days. The percentage of cumulative release was about 61. 5% within 60 days. High density image in the root canal orifice could be seen in Ca（ OH）228 d group,while in S-G-CP group,it could be seen earlier in 7 d,14 d,and 28 d group. The HE stain of S-G-CP 7d and 28 d group shows difference with Ca（ OH）2group in the progress of repairtive dentinogenesis,and the S-G-CP group shows better histocompatibility and earilier repairtive dentinogenesis. Conclusions： The chitosan thermosensitive hydrogel as a carrier,loaded simvastatin,has a sustainable release of the active simvastatin. Animal experiments,simvastatin chitosan gel for vital pulp after direct pulp capping,show its potency in promoting the tertiary dentinogenesis. It is an experimental evidence for simvastatin as a direct pulp capping material in vivo.