Background Mitomycin C (MMC) is still irreplaceable until now.While it's current administration method has proved less than effective in the treatment of refractory glaucoma.To construct a MMC sustained release system which can maintain effective concentration and reduce toxicity is important for postoperative scarring regulation after glaucoma filtration surgery.Objective To evaluate the postoperative effect of use PTMC-F127-PTMC thermosensitive hydrogel as a new drug delivery carrier to sustained release MMC in rabbit trabeculactory.Methods Sixty rabbits,aged 10 to 14 weeks,were divided into 5 trabeculectomy groups in accordance with the random number table,including surgery only group,blank PTMC-F127-PTMC group and three sustained groups with 0.1 ml PTMC-F127-PTMC loaded with 0.05,0.10,0.20 g/L MMC injected after surgery.The MMC concentration of anterior chamber aqueous in three sustained release group with 0.1 ml PTMC-F127-PTMC loaded with 0.05,0.1,0.2 g/L MMC injected after surgery were tested by Guangzhou Analysis and Testing Center using high performance liquid chromatograph-mass spectrometer (HPLC-MS).At 3,7 days postoperatively,0.1 ml aqueous humor from 2 random selected rabbits in each group was extracted using 1 ml syringe with 30G needles from corneal limbus.At postoperative 1,3,5,7,10,14,28 days,bleb width and depth were calculated with caliper measurements and height was graded semiquantitatively by slit-lamp examinations,intraocular pressure (IOP) was measured with Tonopen.And corneal endothelial cell densities were examined by corneal endothelial counting before and 28 days after surgery.Sequential sections of the operative region were prepared and stained with hematoxylin and eosin and proliferating cell nuclear antigen (PCNA) after taking off the eyeballs from dead rabbits at 28 days later.Results MMC could be sustained released from PTMC-F127-PTMC hydrogel for more than 20 days.The mean postoperative bleb survival time in trabeculectomy surgery only group,blank hydrogel group and three sustained release groups were (5.3 ± 0.4),(5.5 ± 0.4),(12.2 ± 1.0),(25.1 ± 0.9),(26.7 ± 0.7) days respectively,the difference between each group was significantly (F =123.200,P =0.000).0.05 g/L MMC sustained release group has a better bleb survival time than that of surgery only group and blank hydrogel group (P =0.000).Compared with other groups,0.10 g/L and 0.20 g/L MMC sustained group has the longest bleb survival time (P =0.000),and more obvious IOP downtrending (F=53 010.000,P＜0.01).But the difference between the two groups was not significant.There was no difference in cornea endothelia cells counts between each group and no MMC was detected in aqueous humors.Histopathology test shows that the inflammatory response and fibrosis were lighter in MMC sustained release group,with stronger proliferation inhibition.Conclusions PTMC-F127-PTMC thermosensitive hydrogel can be a new drug delivery carrier to sustained release MMC.Sustain release MMC can extent bleb survival time with low toxicity.%背景 难治性青光眼患者抗青光眼术中单次应用丝裂霉素C(MMC)并不能满足术后抗滤过区瘢痕化的需求.构建MMC载药缓释系统可维持术区MMC的有效药物浓度和持续抗瘢痕化作用,同时减少药物对眼组织的不良反应,对青光眼滤过术后瘢痕化的调控具有重要意义. 目的 探讨使用聚三亚甲基碳酸酯(PTMC)-F127-PTMC温敏型水凝胶作为MMC的药物载体对兔眼小梁切除术后瘢痕的抑制作用. 方法 将10 ～ 14周龄的新西兰白兔60只行小梁切除术,然后按随机数字表法分成单纯小梁切除术组,术后注射含0.05、0.10、0.20 g/L MMC的PTMC-F127-PTMC组以及空白PTMC-F127-PTMC组,均注射0.1ml.于术后第3天、第7天随机选取0.05、0.10、0.20 g/L MMC的PTMC-F127-PTMC组实验兔各2只眼,用30 G针头从角膜缘进针,取0.1 ml房水送至广州市分析测试中心进行高效液相色谱法-质谱联用分析(HPLC-MS)检测房水内MMC质量浓度;于术后第1、3、5、7、10、14、28天用卡尺测量滤过泡的宽度和长度,半定量估测滤过泡的高度以及用Tonopen眼压计测量实验眼眼压,术前和术后28 d用角膜内皮计数仪进行角膜内皮细胞计数;上述检查后处死动物并摘除眼球,制备眼球组织切片进行苏木精-伊红染色,光学显微镜下检查眼球组织的组织病理学改变.结果 PTMC-F127-PTMC水凝胶在体外可缓释MMC达20 d以上.术后单纯小梁切除术组,空白PTMC-F127-PTMC组,0.05、0.10、0.20 g/L MMC缓释组兔眼滤过泡平均生存时间分别为(5.3±0.4)、(5.5±0.4)、(12.2±1.0)、(25.1±0.9)、(26.7±0.7)d,各组间差异有统计学意义(F=123.200,P=0.000).0.05g/LMMC PTMC-F127-PTMC组的滤过泡生存时间长于单纯小梁切除术组和空白PTMC-F127-PTMC组(均P=0.000).0.10 g/L MMC和0.20 g/L MMC的PTMC-F127-PTMC组滤过泡的生存时间长于其余各组,差异均有统计意义(均P=0.000),此两组术后眼压降低趋势与其余各组的差异有统计意义(F=53 010.000,P＜0.01),但两组之间差异无统计意义(P＞0.05).各组间术后28 d角膜内皮数目的改变差异均无统计意义(P＞0.05),各组房水内均未检测到MMC.组织病理学检查发现,3个MMC缓释组炎症反应及纤维化程度比单纯小梁切除术组和空白PTMC-F127-PTMC组轻,而抑制增生作用更强. 结论 PTMC-F127-PTMC水凝胶可作为缓释载体,负载并缓释不同质量浓度的MMC.MMC缓释组能够在较低毒性作用下有效延长滤过泡的生存时间,调控兔眼小梁手术后的瘢痕化.
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