中华实验眼科杂志
中華實驗眼科雜誌
중화실험안과잡지
CHINESE JOURNAL OF EXPERIMENTAL OPHTHALMOLOGY
2011年
6期
495-500
,共6页
陈玮志%任泽钦%董建强%王喻%黎晓新
陳瑋誌%任澤欽%董建彊%王喻%黎曉新
진위지%임택흠%동건강%왕유%려효신
小梁切除术%滤过泡%贝伐单抗%纤维化%血管化%结膜下注射
小樑切除術%濾過泡%貝伐單抗%纖維化%血管化%結膜下註射
소량절제술%려과포%패벌단항%섬유화%혈관화%결막하주사
Trabeculectomy%Bleb%Bevacizumab%Fibrosis%Vascularization%Subconjunctival injection
背景 贝伐单抗是第一个完整长度的人抗血管内皮生长因子(VEGF)单克隆抗体,已作为抑制新生血管的药物而广泛用于眼科临床.然而,作为小梁切除术后抑制伤口及滤过泡的纤维化及抗血管生成的药物,贝伐单抗多次大剂量使用的安全性和有效性尚待评估.目的 评估大剂量贝伐单抗结膜下多次注射抗小梁切除滤过术后滤过泡瘢痕化的安全性及有效性.方法 采用自身双眼配对的研究设计.对新西兰白兔18只36只眼行小梁切除术滤过手术,动物左眼在术后即刻及术后第3、5、7天于滤过泡结膜下注射25g/L贝伐单抗0.1ml,右眼术后不进行注射作为对照眼.术后间隔2 d裂隙灯下观察滤过泡形态并根据Moorefield滤过泡分级系统进行分级.分别于术后第10、20、30天各摘除12只眼球行苏木精-伊红染色评估细胞的性质,用Masson染色评估成纤维细胞化程度,并以抗血管性血友病因子(anti-vWf)免疫组织化学染色评估每组兔眼的血管化程度.结果 与对照组相比,贝伐单抗治疗眼的滤过泡大且更为弥漫,术后第7天贝伐单抗治疗组与自身对照组眼滤过泡面积分别为(2.48±0.22)cm2和(1.73±0.27)cm2,差异有统计学意义(t=5.194,P<0.05).贝伐单抗治疗眼的滤过泡生存天数(21.00±1.56)d与对照组(12.50±1.97)d相比明显延长,差异有统计学意义(P=0.005).组织学及免疫组织化学分析证实,与对照组相比,在术后20d时,贝伐单抗治疗眼的滤过泡及邻近组织结膜的血管化程度明显减少,2组间vWf阳性染色吸光度值的平均差值为14 320.7±4134.9,差异有统计学意义(t=12.275,P<0.05);而术后30d时贝伐单抗治疗眼的成纤维细胞沉积明显减少,2组间成纤维细胞阳性染色面积的平均差值为0.27±0.03,差异有统计学意义(t=15.980,P<0.05).结论 兔眼小梁切除术后多次结膜下注射贝伐单抗可有效地延长滤过泡的生存时间,在术后30d贝伐单抗能减轻滤过泡和邻近结膜组织的血管化程度.此外,贝伐单抗在术后滤过泡及邻近组织血管化的末期可显著抑制成纤维细胞介导的组织增生.
揹景 貝伐單抗是第一箇完整長度的人抗血管內皮生長因子(VEGF)單剋隆抗體,已作為抑製新生血管的藥物而廣汎用于眼科臨床.然而,作為小樑切除術後抑製傷口及濾過泡的纖維化及抗血管生成的藥物,貝伐單抗多次大劑量使用的安全性和有效性尚待評估.目的 評估大劑量貝伐單抗結膜下多次註射抗小樑切除濾過術後濾過泡瘢痕化的安全性及有效性.方法 採用自身雙眼配對的研究設計.對新西蘭白兔18隻36隻眼行小樑切除術濾過手術,動物左眼在術後即刻及術後第3、5、7天于濾過泡結膜下註射25g/L貝伐單抗0.1ml,右眼術後不進行註射作為對照眼.術後間隔2 d裂隙燈下觀察濾過泡形態併根據Moorefield濾過泡分級繫統進行分級.分彆于術後第10、20、30天各摘除12隻眼毬行囌木精-伊紅染色評估細胞的性質,用Masson染色評估成纖維細胞化程度,併以抗血管性血友病因子(anti-vWf)免疫組織化學染色評估每組兔眼的血管化程度.結果 與對照組相比,貝伐單抗治療眼的濾過泡大且更為瀰漫,術後第7天貝伐單抗治療組與自身對照組眼濾過泡麵積分彆為(2.48±0.22)cm2和(1.73±0.27)cm2,差異有統計學意義(t=5.194,P<0.05).貝伐單抗治療眼的濾過泡生存天數(21.00±1.56)d與對照組(12.50±1.97)d相比明顯延長,差異有統計學意義(P=0.005).組織學及免疫組織化學分析證實,與對照組相比,在術後20d時,貝伐單抗治療眼的濾過泡及鄰近組織結膜的血管化程度明顯減少,2組間vWf暘性染色吸光度值的平均差值為14 320.7±4134.9,差異有統計學意義(t=12.275,P<0.05);而術後30d時貝伐單抗治療眼的成纖維細胞沉積明顯減少,2組間成纖維細胞暘性染色麵積的平均差值為0.27±0.03,差異有統計學意義(t=15.980,P<0.05).結論 兔眼小樑切除術後多次結膜下註射貝伐單抗可有效地延長濾過泡的生存時間,在術後30d貝伐單抗能減輕濾過泡和鄰近結膜組織的血管化程度.此外,貝伐單抗在術後濾過泡及鄰近組織血管化的末期可顯著抑製成纖維細胞介導的組織增生.
배경 패벌단항시제일개완정장도적인항혈관내피생장인자(VEGF)단극륭항체,이작위억제신생혈관적약물이엄범용우안과림상.연이,작위소량절제술후억제상구급려과포적섬유화급항혈관생성적약물,패벌단항다차대제량사용적안전성화유효성상대평고.목적 평고대제량패벌단항결막하다차주사항소량절제려과술후려과포반흔화적안전성급유효성.방법 채용자신쌍안배대적연구설계.대신서란백토18지36지안행소량절제술려과수술,동물좌안재술후즉각급술후제3、5、7천우려과포결막하주사25g/L패벌단항0.1ml,우안술후불진행주사작위대조안.술후간격2 d렬극등하관찰려과포형태병근거Moorefield려과포분급계통진행분급.분별우술후제10、20、30천각적제12지안구행소목정-이홍염색평고세포적성질,용Masson염색평고성섬유세포화정도,병이항혈관성혈우병인자(anti-vWf)면역조직화학염색평고매조토안적혈관화정도.결과 여대조조상비,패벌단항치료안적려과포대차경위미만,술후제7천패벌단항치료조여자신대조조안려과포면적분별위(2.48±0.22)cm2화(1.73±0.27)cm2,차이유통계학의의(t=5.194,P<0.05).패벌단항치료안적려과포생존천수(21.00±1.56)d여대조조(12.50±1.97)d상비명현연장,차이유통계학의의(P=0.005).조직학급면역조직화학분석증실,여대조조상비,재술후20d시,패벌단항치료안적려과포급린근조직결막적혈관화정도명현감소,2조간vWf양성염색흡광도치적평균차치위14 320.7±4134.9,차이유통계학의의(t=12.275,P<0.05);이술후30d시패벌단항치료안적성섬유세포침적명현감소,2조간성섬유세포양성염색면적적평균차치위0.27±0.03,차이유통계학의의(t=15.980,P<0.05).결론 토안소량절제술후다차결막하주사패벌단항가유효지연장려과포적생존시간,재술후30d패벌단항능감경려과포화린근결막조직적혈관화정도.차외,패벌단항재술후려과포급린근조직혈관화적말기가현저억제성섬유세포개도적조직증생.
Background Bevacizumab is primarily aimed at pathologic angiogenesis for off-label uses such as the treatment of ocular neovascular disorders.However,as a new anti-fibrotic and anti-angiogenic agent following trabeculectomy,the safety and efficacy of bevacizumab by multiple-time and high-dose subconjunctival injection are still under study.Objective This study was to assess the safety and efficacy of bevacizumab after multiple-time and high-dose subconjunctival injections.Methods Regular trabeculectomy filtration surgery was performed on both eyes of 18 clean New Zealand White rabbits 0.1ml of bevacizumab(25g/L) was subconjunctivally injected intraoperatively and 3,5,7 days postoperatively in the left eyes of rabbits,and no any intervene in the right eyes were as normal controls.Bleb morphology was examined every 2 days and graded based on Moorefield's criteria and compared between the bevacizumab-treated eyes and normal saline(NS) eyes.The animals were sacrificed at 10,20 and 30 days after surgery respectively.The histopathological changes of the blebs were detected by hematoxylin and eosin stain to evaluate the cellular element around the bleb,and Masson stain was used to assess the degree of fibroblast proliferation.The degree of vascularity of bleb was identified by anti-vWf stain.Approval of this protocol was obtained and permitted from People's Hospital Institutional Animal Care and Use Committee of Peking University.The use of experimental animals complied with the Regulation for the Administration of Affair Concerning Experimental Animals by State Science and Technology Commission.Results Compared to the NS-treated eyes,bevacizumab-treated eyes showed the larger and more diffusely elevated blebs with the significant difference(2.48±0.22cm2 versus 1.73±0.27cm2,t=5.194,P＜0.05).The survival time of the filtration bleb in bevacizumab panel was longer in bevacizumab-treated eyes compared to control eyes,showing a significantly difference between them(21.0±1.56 days versus 12.5±1.97 days,t=3.830,P=0.005).Histological and immunohistochemical analysis confirmed that bleb and adjacent conjunctiva vascularity(A value) was significantly less in bevacizumab-treated eyes than that in control eyes at 20 days after surgery with the difference value 14320.7±4134.9(t=12.275,P＜0.05),and fibroblast deposition value was evidently diminished after bevacizumab treatment at 30 days following surgery in comparison with control eyes with the mean difference 0.27±0.03(t=15.980,P＜0.05＝.Conclusion Repeated subconjunctival injection of bevacizumab can effectively prolong the survival time of bleb in a rabbit model of trabeculectomy and limit the degree and area of vascularization in 30 days following surgery.Bevacizumab inhibit fibroblast-meditated tissue formation significantly in the later phase of vascularization after trabeculectomy.
