中华实验眼科杂志
中華實驗眼科雜誌
중화실험안과잡지
CHINESE JOURNAL OF EXPERIMENTAL OPHTHALMOLOGY
2012年
5期
428-432
,共5页
秦帅%金中秋%陈晓%王博川%刘宏
秦帥%金中鞦%陳曉%王博川%劉宏
진수%금중추%진효%왕박천%류굉
壳聚糖缓释给药系统%曲安奈德%脉络膜上腔%前部增生性玻璃体视网膜病变
殼聚糖緩釋給藥繫統%麯安奈德%脈絡膜上腔%前部增生性玻璃體視網膜病變
각취당완석급약계통%곡안내덕%맥락막상강%전부증생성파리체시망막병변
Chitosan drug delivery system%Triamcinolone acetonide%Suprachoroidal space%Anterior proliferative vitreoretinopathy
背景 前部增生性玻璃体视网膜病变(aPVR)是多种细胞参与的损伤修复过程,目前临床尚无常规应用于防治aPVR的药物.壳聚糖是一种新型的缓释给药载体,载药量大,药物作用时间长,成为近年来研究的热点. 目的 比较壳聚糖缓释给药系统植入脉络膜上腔与玻璃体腔注射曲安奈德(TA)防治外伤性aPVR的疗效.方法 75只健康青紫蓝兔,应用随机数字表法随机分为空白对照组、TA+壳聚糖组、TA注射组、模型对照组、正常对照组,每组15只兔(15只眼).除正常对照组外,其他各组于兔左眼距角膜缘2.5 mm处10:30～11:30位制作长为5 mm的巩膜穿孔伤,并用11号手术尖刀穿刺深约10 mm,用刀轻划兔眼虹膜睫状体部制作外伤性aPVR模型,空白对照组在脉络膜上腔植入空白壳聚糖,TA+壳聚糖组在脉络膜上腔植入壳聚糖缓释给药系统(载药1mg TA),TA注射组在玻璃体腔注射TA溶液(含1 mg TA),模型对照组仅制作外伤模型.分别于术后2、5、8周利用超声生物显微镜(UBM)观察各组睫状体增厚程度以及有无增生膜形成；术后8周过量麻醉法处死动物并制作眼部组织标本,行组织病理学检查和超微结构观察.结果 组织学检查表明,实验后8周空白对照组,TA注射组、模型对照组兔睫状体组织均明显水肿,可见炎性细胞浸润,TA+壳聚糖组兔睫状体组织水肿较轻.电子显微镜下空白对照组、模型对照组兔睫状体组织细胞器明显损伤,TA+壳聚糖组损伤减轻.UBM检查显示TA+壳聚糖组兔睫状体组织及虹膜为轻度异常,而空白对照组、TA注射组、模型对照组可见明显异常.术后2、5、8周,5个组睫状体厚度值的比较差异均有统计学意义(F=212.938、515.323、447.919,P＜0.01).与正常对照组相比,各时间点空白对照组、模型对照组、TA注射组兔睫状体组织均增厚,差异均有统计学意义(P＜0.05),而TA+壳聚糖组睫状体厚度值接近正常对照组(2周:0.484±0.075 vs.0.327±0.094；5周:0.422±0.089 vs.0.327±0.094;8周:0.418±0.085 vs.0.327±0.094),差异均无统计学意义(P＞0.05).结论 载药TA壳聚糖缓释给药系统能够抑制虹膜、睫状体等的增生,防治外伤性aPVR的形成.
揹景 前部增生性玻璃體視網膜病變(aPVR)是多種細胞參與的損傷脩複過程,目前臨床尚無常規應用于防治aPVR的藥物.殼聚糖是一種新型的緩釋給藥載體,載藥量大,藥物作用時間長,成為近年來研究的熱點. 目的 比較殼聚糖緩釋給藥繫統植入脈絡膜上腔與玻璃體腔註射麯安奈德(TA)防治外傷性aPVR的療效.方法 75隻健康青紫藍兔,應用隨機數字錶法隨機分為空白對照組、TA+殼聚糖組、TA註射組、模型對照組、正常對照組,每組15隻兔(15隻眼).除正常對照組外,其他各組于兔左眼距角膜緣2.5 mm處10:30～11:30位製作長為5 mm的鞏膜穿孔傷,併用11號手術尖刀穿刺深約10 mm,用刀輕劃兔眼虹膜睫狀體部製作外傷性aPVR模型,空白對照組在脈絡膜上腔植入空白殼聚糖,TA+殼聚糖組在脈絡膜上腔植入殼聚糖緩釋給藥繫統(載藥1mg TA),TA註射組在玻璃體腔註射TA溶液(含1 mg TA),模型對照組僅製作外傷模型.分彆于術後2、5、8週利用超聲生物顯微鏡(UBM)觀察各組睫狀體增厚程度以及有無增生膜形成；術後8週過量痳醉法處死動物併製作眼部組織標本,行組織病理學檢查和超微結構觀察.結果 組織學檢查錶明,實驗後8週空白對照組,TA註射組、模型對照組兔睫狀體組織均明顯水腫,可見炎性細胞浸潤,TA+殼聚糖組兔睫狀體組織水腫較輕.電子顯微鏡下空白對照組、模型對照組兔睫狀體組織細胞器明顯損傷,TA+殼聚糖組損傷減輕.UBM檢查顯示TA+殼聚糖組兔睫狀體組織及虹膜為輕度異常,而空白對照組、TA註射組、模型對照組可見明顯異常.術後2、5、8週,5箇組睫狀體厚度值的比較差異均有統計學意義(F=212.938、515.323、447.919,P＜0.01).與正常對照組相比,各時間點空白對照組、模型對照組、TA註射組兔睫狀體組織均增厚,差異均有統計學意義(P＜0.05),而TA+殼聚糖組睫狀體厚度值接近正常對照組(2週:0.484±0.075 vs.0.327±0.094；5週:0.422±0.089 vs.0.327±0.094;8週:0.418±0.085 vs.0.327±0.094),差異均無統計學意義(P＞0.05).結論 載藥TA殼聚糖緩釋給藥繫統能夠抑製虹膜、睫狀體等的增生,防治外傷性aPVR的形成.
배경 전부증생성파리체시망막병변(aPVR)시다충세포삼여적손상수복과정,목전림상상무상규응용우방치aPVR적약물.각취당시일충신형적완석급약재체,재약량대,약물작용시간장,성위근년래연구적열점. 목적 비교각취당완석급약계통식입맥락막상강여파리체강주사곡안내덕(TA)방치외상성aPVR적료효.방법 75지건강청자람토,응용수궤수자표법수궤분위공백대조조、TA+각취당조、TA주사조、모형대조조、정상대조조,매조15지토(15지안).제정상대조조외,기타각조우토좌안거각막연2.5 mm처10:30～11:30위제작장위5 mm적공막천공상,병용11호수술첨도천자심약10 mm,용도경화토안홍막첩상체부제작외상성aPVR모형,공백대조조재맥락막상강식입공백각취당,TA+각취당조재맥락막상강식입각취당완석급약계통(재약1mg TA),TA주사조재파리체강주사TA용액(함1 mg TA),모형대조조부제작외상모형.분별우술후2、5、8주이용초성생물현미경(UBM)관찰각조첩상체증후정도이급유무증생막형성；술후8주과량마취법처사동물병제작안부조직표본,행조직병이학검사화초미결구관찰.결과 조직학검사표명,실험후8주공백대조조,TA주사조、모형대조조토첩상체조직균명현수종,가견염성세포침윤,TA+각취당조토첩상체조직수종교경.전자현미경하공백대조조、모형대조조토첩상체조직세포기명현손상,TA+각취당조손상감경.UBM검사현시TA+각취당조토첩상체조직급홍막위경도이상,이공백대조조、TA주사조、모형대조조가견명현이상.술후2、5、8주,5개조첩상체후도치적비교차이균유통계학의의(F=212.938、515.323、447.919,P＜0.01).여정상대조조상비,각시간점공백대조조、모형대조조、TA주사조토첩상체조직균증후,차이균유통계학의의(P＜0.05),이TA+각취당조첩상체후도치접근정상대조조(2주:0.484±0.075 vs.0.327±0.094；5주:0.422±0.089 vs.0.327±0.094;8주:0.418±0.085 vs.0.327±0.094),차이균무통계학의의(P＞0.05).결론 재약TA각취당완석급약계통능구억제홍막、첩상체등적증생,방치외상성aPVR적형성.
Background Anterior proliferative vitreoretinopathy (aPVR) is a tissue injury and repair progress,and treatment of aPVR is very important in clinic.Chitosan drug delivery system is becoming a hot spot for its large lading dose and long acting duration. Objective The present study was to investigate the curative effect of a triamcinolone acetonide (TA) drug delivery system after implantation into the suprachoroidal space to treat traumatic aPVR. Methods aPVR models were created in the left eyes of 65 healthy pigment rabbits by performing a 5 mm penetrating incision 2.5 mm posterior to limbum at 10:30-11:30.The animals were randomly divided into 4groups.Blank chitosan was implanted into the suprachoroidal space as the blank control group.Chitosan with 1 mg TA was implanted in the TA + chitosa group.The TA solution ( containing 1 mg TA) was intravitreally injected in the TA injection group.Fifteen models were used as the traumatic control group.Another 15 left eyes of normal pigment rabbits were used as the normal control group.The thickness of the ciliary tissue was measured using a ultrasound biomicroscope(UBM) 3,5 and 8 weeks after operation.The animals were sacrificed by excessive anesthesia and eyeballs were obtained for histopathological and ultrastructural examinations. Results Histopathological examination showed the edema of the ciliary tissue and inflammatory cells infiltration in the blank control group,TA injection group and model control group,but mild response was seen in the TA + chitosa group.Severe damage in the ciliary tissue and subcellular organelle was found in the blank and model control groups,but mild damage was detected in the TA + chitosa group under the transmission electron microscope.UBM examination revealed that obvious abnormalities were visible in the ciliary and iris tissue in the blank control group,TA injection group and traumatic control group,but a mild abnormality was seen in the TA + chitosa group.Significant differences in ciliary thickness were exhibited among the 5 groups 2,5 and 8 weeks after operation (F =212.938,515.323,447.919,P＜0.01 ).Compared with the normal control group,ciliary thickness significantly increased in the blank control group and normal control group at various time points (all P＜0.05 ),but that in the TA + chitosa group was significantly lower than the normal control group at various time points ( two weeks:0.484±0.075 vs.0.327 ±0.094 ; five weeks:0.422 ±0.089vs.0.327±0.094 ;eight weeks:0.418±0.085 vs.0.327±0.094) (all P＞0.05). Conclusions The chitosan drug delivery system with TA suppresses the excessive proliferation of injured ocular tissue after implantation into the suprachoroidal space,which prevents the formation and development of aPVR.
