Anti-proliferation effects of Sirolimus sustained delivery film in rabbit glaucoma filtration surgery
Anti-proliferation effects of Sirolimus sustained delivery film in rabbit glaucoma filtration surgery
复制标题
西罗莫司缓释膜在兔青光眼滤过手术中的抗增殖作用
DOI：
--
复制
发表时间：
2011-09
期刊：
影响因子：
--
通讯作者：
卓业鸿
中科院分区：
文献类型：
--
作者：
卓业鸿
目的观察西罗莫司缓释膜对兔青光眼滤过术后瘢痕形成的影响，并探讨其作用机制。方法新西兰白色兔64只，随机分为4组：西罗莫司缓释药膜治疗组（A组）、无药膜治疗组（B组）、30 ng/ml西罗莫司海绵治疗组（C组）和无药膜治疗组（D组），每组16只。术后随访28天，观察眼压、滤过泡形态学改变、前房闪辉、角膜内皮细胞计数及并发症。A组术后定期采集眼房水，测定西罗莫司浓度。分别于术后第7、14、28天处死动物，HE染色、Masson染色观察各组成纤维细胞肥大、炎性细胞浸润及新生胶原纤维增生情况。术后第28天采用免疫组化和末端脱氧核苷酸转移酶介导的dUTP缺口末端标记法（TUNEL）检测增殖细胞核抗原（PCNA）和成纤维细胞凋亡。结果西罗莫司缓释药膜组（A组）和西罗莫司单药组（C组）均耐受良好，与未给药组（B组和D组）相比，bleB生存期明显延长（P <0.001）。A组滤过泡存活时间最长（P <0.001）。末次随访时，A组与其他组之间的IOP读数存在显著差异（p <0.05）。A组血药浓度稳定2周以上，由第3天的（10.56 ± 0.05）ng/ml降至第14天的（7.74 ± 0.05）ng/ml。A组角膜内皮细胞数量术前与术后比较差异无统计学意义。组织学检查表明，与无药物治疗组相比，接受西罗莫司治疗的眼睛，尤其是西罗莫司缓释膜，结膜下成纤维细胞瘢痕组织形成明显减少，结膜下炎性细胞浸润和新胶原沉积的证据极少。免疫组化结果显示A组PCNA阳性表达率（16.25 ± 3.24%）明显低于其他各组（P <0.01）。TUNEL法显示A组和C组手术区周围成纤维细胞凋亡率分别为9.75 ± 1.71%和8.50 ± 1.92%，明显高于B和D组（p <0.01）。结论西罗莫司缓释药膜可抑制兔眼滤过手术部位炎性细胞活性，抑制成纤维细胞增殖活性，诱导成纤维细胞凋亡。结果表明，在青光眼手术中抗瘢痕治疗是一种安全有效的治疗策略。
Purpose To investigate the efficacy, safety, and mechanisms of Sirolimus sustained delivery film on prevention of scar formation in a rabbit model of glaucoma filtration surgery. Methods Sixty-four New Zealand white rabbits who underwent trabeculectomy in the right eye were randomly allocated to one of the four treatment regimens: Sirolimus sustained delivery film treatment group (Group A), or drug-free film treatment group (Group B), or 30 ng/ml Sirolimus-soaked sponge treatment group (Group C), or no adjunctive treatment group (Group D), and each group consists of 16 rabbits. Intraocular pressure (IOP), morphologic changes of bleb, anterior chamber flare, and corneal endothelial cell count and complications were evaluated over a 28-day period follow-up time. Aqueous humor samples were gathered from Group A, and the concentration of Sirolimus was measured regularly post-operation. Rabbits were sacrificed on the 7th, 14th, and 28th day post-operation separately, and the fibroblast hypertrophy, infiltration of inflammatory, and proliferation of new collagen fiber formation in each group were evaluated with HE and Masson staining. Proliferative cell nuclear antigen (PCNA) and fibroblast apoptosis were evaluated by immunohistochemistry and terminal deoxynucleotidyl transferasemediated dUTP nick end labeling (TUNEL) assay at the 28th day post-operation. Results Both Sirolimus sustained delivery film (Group A) and Sirolimus alone (Group C) were well tolerated in this model, and significantly prolonged bleb survival compared with no drug treatment group (Group B and D; p<0.001). Group A had the longest bleb survival time in comparison with other groups (p<0.001). There were significant differences in IOP readings between Group A and other groups at the last follow-up (p<0.05). The concentration of Group A maintained stable for over 2 weeks, drops from (10.56 ±0.05) ng/ml at day 3 to (7.74 ±0.05) ng/ml at day 14. The number of corneal endothelial cells of Group A was not statistically significant between pre and post-operation. Histologic examination demonstrated that eyes treated with Sirolimus, especially the Sirolimus sustained delivery film, showed an obvious reduction in subconjunctival fibroblast scar tissue formation compared with no drug treatment groups, and had minimal evidence of inflammatory cell infiltration and new collagen deposition in the subconjunctiva. Immunohistochemistry assay showed that PCNA-expression was lower in the Group A (16.25±3.24%) compared to other groups (p<0.01). TUNEL assay showed a significant increase in the number of apoptotic fibroblasts around the surgical area in Group A and Group C (9.75±1.71% and 8.50±1.92%) compared to the Group B and D (p<0.01). Conclusions Sirolimus drug sustained delivery film can inhibit inflammatory cell activity, impede fibroblast proliferation activity, and induce fibroblast apoptosis in the filtration surgery sites in rabbit. The results indicate a safe and effective treatment strategy in anti-scaring treatment in glaucoma surgery.
登录
查看更多内容
影响因子：
4.2
作者：
B. Rubin;C. Chan;M. Burnier;L. Munion;J. Freedman
通讯作者：
B. Rubin;C. Chan;M. Burnier;L. Munion;J. Freedman
影响因子：
1.4
作者：
I. Durak;Z. Ozbek;A. Yaman;M. Soylev;G. Cıngıl
通讯作者：
I. Durak;Z. Ozbek;A. Yaman;M. Soylev;G. Cıngıl
影响因子：
13.7
作者：
Y. Oshima;T. Sakamoto;T. Nakamura;Y. Tahara;Y. Goto;T. Ishibashi;H. Inomata
通讯作者：
Y. Oshima;T. Sakamoto;T. Nakamura;Y. Tahara;Y. Goto;T. Ishibashi;H. Inomata
影响因子：
4.3
作者：
Cagiannos, C;Abul-Khoudoud, OR;Fabian, TC
通讯作者：
Fabian, TC
影响因子：
5.1
作者：
Lü JM;Wang X;Marin-Muller C;Wang H;Lin PH;Yao Q;Chen C
通讯作者：
Chen C