汉防己甲素缓释系统对兔眼滤过术后瘢痕化的抑制作用

Anti-cicatricial effect of tetrandrine drug delivery system in glaucoma filtration surgery in rabbit

背景滤过泡瘢痕化是抗青光眼滤过性手术失败的主要原因，研究表明汉防己甲素（Tet）可抑制体外培养的人Tenon囊成纤维细胞的增生，从而具有抗滤过术后瘢痕化的潜在作用。目的了解兔眼滤过性手术中植入Tet缓释系统（DDS）抑制瘢痕形成的作用。方法将18只新西兰白兔36只眼行滤过性小梁切除术，按随机数字表法将白兔随机分为3组，每组12只眼，术中按照分组将含0．3mgTet、0．2mgTet的DDS及无药物的空白DDS分别植入各组兔眼结膜瓣下。术后l、4、7、10、14d在裂隙灯下依据邻近角膜厚度标准的滤过泡面积对滤过泡进行评分；术后7d、14d行活体滤过泡组织的共焦显微镜检查，然后制备滤过泡组织学标本行常规组织病理学检查。结果各组的平均滤过泡得分显示，术后4～14dTetDDS组兔眼的滤过泡评分明显高于空白DDS组，差异有统计学意义（P〈0．01）；术后7～14d，0．3mgTet组兔眼的滤过泡评分高于0．2mgTet组，差异有统计学意义（P〈0．05）。光学显微镜下及共焦显微镜下滤过泡形态学观察显示，术后7d、14dTetDDS组兔眼均可见清晰的滤过泡腔隙，滤过泡上皮下平均囊腔数量值及囊腔面积均大于空白DDS组（P〈0．01），0．3mgTet组兔眼滤过泡上皮下平均囊腔数量值及囊腔面积均大于0．2mgTet组，差异有统计学意义（P〈0．05）。组织病理学研究还表明，0．3mgTet组兔眼滤过泡组织中炎性细胞浸润明显轻于0．2mgTet组和空白DDS组。结论研究结果表明TetDDS能有效抑制滤过性手术后成纤维细胞的增生，提高兔眼滤过性手术的成功率。

Background Scarring of the filtering bleb is a main cause of filtering surgical failure in glaucoma. It has been reported that tetrandrine could suppress the proliferation of cultured human fibroblast of Tenons capsule in vitro and thus has the potential effect to prevent scarring after the filtering surgery. Objective Present study was to investigate the anti-eicatricial effect of tetrandrine drug delivery system （ Tet DDS） during filtration surgery. Methods Filtration surgery was performed in bilateral eyes of 18 New Zealand white rabbits. The Tet DDS with 0.3 mg Tet,0.2 mg Tet or free-Tet were implanted subeunjunctially during the surgery. The filtering blebs were scored in 1 day, 4, 7, 10, 14 days after referring to the corneal thickness and bleb range under the slit-lamp biomicroscopy. The morphology of filtering bleb was assessed by in vivo confocal microscopy in 7 and 14 days after operation. The filtering bleb specimen was prepared in 7 and 14 days for the histopathological examination. Results The filtering bleb scores in Tet DDS implantation groups were significantly higher than those in free-Tet DDS group from 4 days through 14 days after trabeculectomy（P〈O. Ol ） ,and the scores showed a considerably increase in O. 3 mg Tet DDS group compared with 0.2 mg Tet DDS group from 7 days through 14 days after trabeculectomy（P〈0.05）. The filtering blebs of Tet DDS implantation groups were found with distinct subepithelial cystic spaces under the light microscopy and in vivo confocal microscopy on the 7th day and 14th day after surgery. Compared with free-Tet DDS group,the numbers of subepithelial microcysts were much more（P〈0.01 ） and the area of microcysts was larger（P〈 0.01 ） in Tet DDS group. The filtering tissue presented with more subepithelial microcysts and larger microcysts range in 0.3 mg Tet DDS group than 0.2 mg Tet DDS group in 7 and 14 days after operation（P〈0.05 ）. The inflammatory cell infiltration was milder in 0.3 mg Tet DDS group in comparison with 0.2 mg Tet DDS group and free-Ted DDS group. Conclusion Tet DDS has strong inhibitory effects on inflammatory cells activity and fibroblast activity the early stage after filtering surgery and therefore improve the surgery success rate.