CAJ | 학술논문

目的观察抗血管内皮生长因子bevacizumab(商品名Avastin)兔眼玻璃体腔重复注射的眼内安全性.方法 14只青紫兰兔分为3组,其中12只兔的右眼设为实验组,左眼设为实验对照组,2只兔为正常对照组.实验组右眼予以25 mg/ml的bevacizumab玻璃体腔注射,实验组根据不同注射剂量分为2.5、5.0 mg 2个剂量组,左眼分别注射等剂量0.9%生理盐水作为实验对照.玻璃体腔共注射3次,每次间隔2周.每次注射前、注射后2 d,第3次注射后1、4周采用裂隙灯显微镜、+90 D前置镜、B型超声、超生生物显微镜(UBM)、光相干断层扫描(OCT)进行临床指标观察,视网膜电图(ERG)和闪光视觉诱发电位(F-VEP)进行视网膜功能检测.第3次注射完毕后1、4周分别摘取眼球进行病理组织学观察和凋亡细胞检测.结果所有实验眼和实验对照眼均未见明显炎症反应,各组眼底未见明显异常,玻璃体无混浊、出血.B型超声、UBM和OCT检查均未见明显改变.注射前后不同剂量实验组与实验对照组、正常对照组眼压、前房闪辉计数比较,差异均无统计学意义(P>0.05).不同剂量实验组与注射前、实验对照组、正常对照组最大反应ERG a、b波比较,差异均无统计学意义(P>0.05).注射前后,F-VEP N1波潜伏期和P1波振幅各组差异均无统计学意义(P>0.05).光学显微镜观察发现,不同剂量实验组第3次注射后1周玻璃体腔可见少量炎症细胞,注射后第4周未见炎症细胞;实验对照组和正常对照组注射前后视网膜组织形态未见明显改变.5.0 mg实验组第3次注射后1周电子显微镜下可见炎症细胞,个别视细胞细胞核呈空泡样改变,其余未见明显异常.凋亡细胞计数显示,第3次注射后1周,5.0mg实验组与2.5、5.0mg实验对照组(Z=0.227)和正常对照组(Z=1.341)组间凋亡细胞数量比较,差异均有统计学意义(P<0.01),第3次注射后4周,各组差异无统计学意义(x2=4.826,P>0.05).结论 5.0 mg bevacizumab在兔眼玻璃体腔多次注射视网膜有一定轻微毒性反应. 目的觀察抗血管內皮生長因子bevacizumab(商品名Avastin)兔眼玻璃體腔重複註射的眼內安全性.方法 14隻青紫蘭兔分為3組,其中12隻兔的右眼設為實驗組,左眼設為實驗對照組,2隻兔為正常對照組.實驗組右眼予以25 mg/ml的bevacizumab玻璃體腔註射,實驗組根據不同註射劑量分為2.5、5.0 mg 2箇劑量組,左眼分彆註射等劑量0.9%生理鹽水作為實驗對照.玻璃體腔共註射3次,每次間隔2週.每次註射前、註射後2 d,第3次註射後1、4週採用裂隙燈顯微鏡、+90 D前置鏡、B型超聲、超生生物顯微鏡(UBM)、光相榦斷層掃描(OCT)進行臨床指標觀察,視網膜電圖(ERG)和閃光視覺誘髮電位(F-VEP)進行視網膜功能檢測.第3次註射完畢後1、4週分彆摘取眼毬進行病理組織學觀察和凋亡細胞檢測.結果所有實驗眼和實驗對照眼均未見明顯炎癥反應,各組眼底未見明顯異常,玻璃體無混濁、齣血.B型超聲、UBM和OCT檢查均未見明顯改變.註射前後不同劑量實驗組與實驗對照組、正常對照組眼壓、前房閃輝計數比較,差異均無統計學意義(P>0.05).不同劑量實驗組與註射前、實驗對照組、正常對照組最大反應ERG a、b波比較,差異均無統計學意義(P>0.05).註射前後,F-VEP N1波潛伏期和P1波振幅各組差異均無統計學意義(P>0.05).光學顯微鏡觀察髮現,不同劑量實驗組第3次註射後1週玻璃體腔可見少量炎癥細胞,註射後第4週未見炎癥細胞;實驗對照組和正常對照組註射前後視網膜組織形態未見明顯改變.5.0 mg實驗組第3次註射後1週電子顯微鏡下可見炎癥細胞,箇彆視細胞細胞覈呈空泡樣改變,其餘未見明顯異常.凋亡細胞計數顯示,第3次註射後1週,5.0mg實驗組與2.5、5.0mg實驗對照組(Z=0.227)和正常對照組(Z=1.341)組間凋亡細胞數量比較,差異均有統計學意義(P<0.01),第3次註射後4週,各組差異無統計學意義(x2=4.826,P>0.05).結論 5.0 mg bevacizumab在兔眼玻璃體腔多次註射視網膜有一定輕微毒性反應.
목적 관찰항혈관내피생장인자bevacizumab(상품명Avastin)토안파리체강중복주사적안내안전성.방법 14지청자란토분위3조,기중12지토적우안설위실험조,좌안설위실험대조조,2지토위정상대조조.실험조우안여이25 mg/ml적bevacizumab파리체강주사,실험조근거불동주사제량분위2.5、5.0 mg 2개제량조,좌안분별주사등제량0.9%생리염수작위실험대조.파리체강공주사3차,매차간격2주.매차주사전、주사후2 d,제3차주사후1、4주채용렬극등현미경、+90 D전치경、B형초성、초생생물현미경(UBM)、광상간단층소묘(OCT)진행림상지표관찰,시망막전도(ERG)화섬광시각유발전위(F-VEP)진행시망막공능검측.제3차주사완필후1、4주분별적취안구진행병리조직학관찰화조망세포검측.결과 소유실험안화실험대조안균미견명현염증반응,각조안저미견명현이상,파리체무혼탁、출혈.B형초성、UBM화OCT검사균미견명현개변.주사전후불동제량실험조여실험대조조、정상대조조안압、전방섬휘계수비교,차이균무통계학의의(P>0.05).불동제량실험조여주사전、실험대조조、정상대조조최대반응ERG a、b파비교,차이균무통계학의의(P>0.05).주사전후,F-VEP N1파잠복기화P1파진폭각조차이균무통계학의의(P>0.05).광학현미경관찰발현,불동제량실험조제3차주사후1주파리체강가견소량염증세포,주사후제4주미견염증세포;실험대조조화정상대조조주사전후시망막조직형태미견명현개변.5.0 mg실험조제3차주사후1주전자현미경하가견염증세포,개별시세포세포핵정공포양개변,기여미견명현이상.조망세포계수현시,제3차주사후1주,5.0mg실험조여2.5、5.0mg실험대조조(Z=0.227)화정상대조조(Z=1.341)조간조망세포수량비교,차이균유통계학의의(P<0.01),제3차주사후4주,각조차이무통계학의의(x2=4.826,P>0.05).결론 5.0 mg bevacizumab재토안파리체강다차주사시망막유일정경미독성반응.
Objective To evaluate the safety repeated intravitreal injection of bevacizumab (Avastin) with different dosage in rabbitst eyes.Methods Fourteen chinchilla rabbits were randomly divided into 3 groups,including both eyes of 2 rabbits in the control group,the right eyes of the other 12 rabbits in the experimental group,and the left eyes of the 12 rabbits in the experimental control group.The eyes in the experimental group underwent intravitreal injection of bevacizumab with the dosage of 2.5 mg/0.1 ml and 5.0 mg/0.2 ml of bevacizumab;the eyes in the experimental control group underwent intravitreal injection of normal saline with the same dosage as in the experimental group.Injections were performed every two weeks and lasted six weeks.Clinical observation and retinal function tests were performed before and two days after every injection.The eyes were sacrificed 1 week and 4 weeks after last intravitreal injection respectively.Electron and optical microscope and TUNEL were performed.Results After intravitreal injection,no obvious anterior chamber flare,abnormal change of the ocular fundus,or vitreous opacity and hemorrhage was observed in all of the eyes.No change was found by indirect ophthalmoscope,B-ultrasonic inspection,ultrasound biomicroscopy and optical coherence tomography.The number of anterior chamber flare before and after the injection with the dosage of 2.5 and 5.0 mg,the difference among the 3 groups didn't differ much from each other (P>0.05).Amplitude and pattern of ERG responses and flash VEP were similar between the control and experimental groups (P>0.05).Some inflammatory cells were found in the some bevacizumab-injected eyes 1 week after injection,and vanished 3 weeks later.The histological configuration of the retina didn't change in both experimental control and the control group.Electron microscopy showed that plasma cells were presented and vacuole-like change was observed in part of the photoreceptor cells in 5.0 mg experimental group 1 week after injections.Cellular apoptosis was observed in the photoreceptor cell layer.The number of apoptotic cells was more in 5.0 mg experimental group than that in the control and experimental control group 1 week after injections (P<0.01).Conclusion Multi intravitreal injection with 5.0 mg bevacizumab may have mild toxicity to the retina in the rabbits.