中华实验眼科杂志
中華實驗眼科雜誌
중화실험안과잡지
CHINESE JOURNAL OF EXPERIMENTAL OPHTHALMOLOGY
2014年
6期
506-511
,共6页
席蕾%赵峰%王涛%刘炳乾%全大萍%葛坚
席蕾%趙峰%王濤%劉炳乾%全大萍%葛堅
석뢰%조봉%왕도%류병건%전대평%갈견
青光眼%丝裂霉素C%缓释%小梁切除术
青光眼%絲裂黴素C%緩釋%小樑切除術
청광안%사렬매소C%완석%소량절제술
Glaucoma%Mitomycin C%Sustained release%Trabeculectomy
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.
揹景 難治性青光眼患者抗青光眼術中單次應用絲裂黴素C(MMC)併不能滿足術後抗濾過區瘢痕化的需求.構建MMC載藥緩釋繫統可維持術區MMC的有效藥物濃度和持續抗瘢痕化作用,同時減少藥物對眼組織的不良反應,對青光眼濾過術後瘢痕化的調控具有重要意義. 目的 探討使用聚三亞甲基碳痠酯(PTMC)-F127-PTMC溫敏型水凝膠作為MMC的藥物載體對兔眼小樑切除術後瘢痕的抑製作用. 方法 將10 ～ 14週齡的新西蘭白兔60隻行小樑切除術,然後按隨機數字錶法分成單純小樑切除術組,術後註射含0.05、0.10、0.20 g/L MMC的PTMC-F127-PTMC組以及空白PTMC-F127-PTMC組,均註射0.1ml.于術後第3天、第7天隨機選取0.05、0.10、0.20 g/L MMC的PTMC-F127-PTMC組實驗兔各2隻眼,用30 G針頭從角膜緣進針,取0.1 ml房水送至廣州市分析測試中心進行高效液相色譜法-質譜聯用分析(HPLC-MS)檢測房水內MMC質量濃度;于術後第1、3、5、7、10、14、28天用卡呎測量濾過泡的寬度和長度,半定量估測濾過泡的高度以及用Tonopen眼壓計測量實驗眼眼壓,術前和術後28 d用角膜內皮計數儀進行角膜內皮細胞計數;上述檢查後處死動物併摘除眼毬,製備眼毬組織切片進行囌木精-伊紅染色,光學顯微鏡下檢查眼毬組織的組織病理學改變.結果 PTMC-F127-PTMC水凝膠在體外可緩釋MMC達20 d以上.術後單純小樑切除術組,空白PTMC-F127-PTMC組,0.05、0.10、0.20 g/L MMC緩釋組兔眼濾過泡平均生存時間分彆為(5.3±0.4)、(5.5±0.4)、(12.2±1.0)、(25.1±0.9)、(26.7±0.7)d,各組間差異有統計學意義(F=123.200,P=0.000).0.05g/LMMC PTMC-F127-PTMC組的濾過泡生存時間長于單純小樑切除術組和空白PTMC-F127-PTMC組(均P=0.000).0.10 g/L MMC和0.20 g/L MMC的PTMC-F127-PTMC組濾過泡的生存時間長于其餘各組,差異均有統計意義(均P=0.000),此兩組術後眼壓降低趨勢與其餘各組的差異有統計意義(F=53 010.000,P＜0.01),但兩組之間差異無統計意義(P＞0.05).各組間術後28 d角膜內皮數目的改變差異均無統計意義(P＞0.05),各組房水內均未檢測到MMC.組織病理學檢查髮現,3箇MMC緩釋組炎癥反應及纖維化程度比單純小樑切除術組和空白PTMC-F127-PTMC組輕,而抑製增生作用更彊. 結論 PTMC-F127-PTMC水凝膠可作為緩釋載體,負載併緩釋不同質量濃度的MMC.MMC緩釋組能夠在較低毒性作用下有效延長濾過泡的生存時間,調控兔眼小樑手術後的瘢痕化.
배경 난치성청광안환자항청광안술중단차응용사렬매소C(MMC)병불능만족술후항려과구반흔화적수구.구건MMC재약완석계통가유지술구MMC적유효약물농도화지속항반흔화작용,동시감소약물대안조직적불량반응,대청광안려과술후반흔화적조공구유중요의의. 목적 탐토사용취삼아갑기탄산지(PTMC)-F127-PTMC온민형수응효작위MMC적약물재체대토안소량절제술후반흔적억제작용. 방법 장10 ～ 14주령적신서란백토60지행소량절제술,연후안수궤수자표법분성단순소량절제술조,술후주사함0.05、0.10、0.20 g/L MMC적PTMC-F127-PTMC조이급공백PTMC-F127-PTMC조,균주사0.1ml.우술후제3천、제7천수궤선취0.05、0.10、0.20 g/L MMC적PTMC-F127-PTMC조실험토각2지안,용30 G침두종각막연진침,취0.1 ml방수송지엄주시분석측시중심진행고효액상색보법-질보련용분석(HPLC-MS)검측방수내MMC질량농도;우술후제1、3、5、7、10、14、28천용잡척측량려과포적관도화장도,반정량고측려과포적고도이급용Tonopen안압계측량실험안안압,술전화술후28 d용각막내피계수의진행각막내피세포계수;상술검사후처사동물병적제안구,제비안구조직절편진행소목정-이홍염색,광학현미경하검사안구조직적조직병이학개변.결과 PTMC-F127-PTMC수응효재체외가완석MMC체20 d이상.술후단순소량절제술조,공백PTMC-F127-PTMC조,0.05、0.10、0.20 g/L MMC완석조토안려과포평균생존시간분별위(5.3±0.4)、(5.5±0.4)、(12.2±1.0)、(25.1±0.9)、(26.7±0.7)d,각조간차이유통계학의의(F=123.200,P=0.000).0.05g/LMMC PTMC-F127-PTMC조적려과포생존시간장우단순소량절제술조화공백PTMC-F127-PTMC조(균P=0.000).0.10 g/L MMC화0.20 g/L MMC적PTMC-F127-PTMC조려과포적생존시간장우기여각조,차이균유통계의의(균P=0.000),차량조술후안압강저추세여기여각조적차이유통계의의(F=53 010.000,P＜0.01),단량조지간차이무통계의의(P＞0.05).각조간술후28 d각막내피수목적개변차이균무통계의의(P＞0.05),각조방수내균미검측도MMC.조직병이학검사발현,3개MMC완석조염증반응급섬유화정도비단순소량절제술조화공백PTMC-F127-PTMC조경,이억제증생작용경강. 결론 PTMC-F127-PTMC수응효가작위완석재체,부재병완석불동질량농도적MMC.MMC완석조능구재교저독성작용하유효연장려과포적생존시간,조공토안소량수술후적반흔화.
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.
