外伤性视神经病动物模型的建立
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摘要
目的 外伤性视神经病(TON)随着目前交通事故的增多而增加，临床上诊断与治疗该病的方法多样，治疗效果各家报道不一，未形成统一的诊治标准，并且缺乏相关的实验研究。尤其在动物实验研究方面，国内研究甚少。我们从建立外伤性视神经病动物模型入手，应用客观的检查方法，建立模拟该病的动物模型，为进一步探讨外伤性视神经病的发病机理、诊治标准及预后提供参考。
方法 选择健康成年家兔2只、家猫2只，处死后解剖观察鼻腔鼻窦及视神经的解剖关系，确定家猫为实验动物。选择健康成年家猫8只，以自身左眼为实验眼，右眼为对照眼，术前检测视觉诱发电位(VISUAL EVOKED POTENTIAL，VEP)。经鼻腔筛蝶窦入路，用自制视神经管损伤器损伤管内段视神经，建立TON模型，检测图形视觉诱发电位(PR-VEP)，观察动物瞳孔对光反应。以PR-VEP波形改变为模型建立成功检测的指标。观察动物分别在术后1h、1d、3d、1w、2w、4w时的PR-VEP波形和瞳孔变化。
结果 家猫的鼻窦结构与视神经走行与人类相似，有完整的视神经管，为较适合的实验动物。内镜下经鼻腔鼻窦入路寻找视神经管方法可行。8只猫损伤后有4只瞳孔不同程度散大，直接对光反应减弱或消失，间接对光反应灵敏，但有4只家猫的瞳孔对光反应双侧无明显差异。PR-VEP中N_(75)P_(100)、P_(100)N_(145)波幅均减小，N_(75)、P_(100)、N_(145)峰潜时均延长。损伤后1h、1d、3d、1w时的N_(75)P_(100)、P_(100)N_(145)波幅分别平均为8.60±1.32uv、7.90±0.39uv；6.81±1.22uv、3.40±0.43uv；6.00±2.07uv、4.50±0.78uv；6.60±1.62uv、3.00±0.78uv。N_(75)、P_(100)、N_(145)各峰潜时分别平均为82.80±0.69ms、120.60±1.36ms、174.00±2.94ms；106.30±7.14ms、136.80±6.17ms、178.20±7.28ms；101.40±5.68ms、144.60±6.16ms、191.40±9.59ms；106.80±10.08ms、148.80±12.02ms、202.80±12.16ms。损伤后2w与4w时PR-VEP的波形引出为一条近似直线，无法测出各波幅及各峰潜时的数值。损伤前与损伤后1h、1d、3d、1w PR-VEP比较为P＜0.05；1h与1d、3d、1w比较P值＜0.05，1d、3d、1w之间两两比较P值＞0.05或＜0.05。
结论 ①家猫的鼻窦结构与视神经走行与人类相似，有完整的视神经管，为较适合的实验动物。②内镜下经鼻腔筛蝶窦入路建立视神经损伤动物模型方法可行；
第一章中文摘要
③视神经管损伤前、后的VEP改变明显，VEP变化可作为外伤性视神经病动物模型的
客观监测指标;瞳孔对光反射不宜作为TON动物模型建立成功与否的检测指标
[Objective] Traumatic Optic Neuropathy(TON) was increasing with the traffic accident. The methods of diagnosis and therapy were variable,the consents and the results were not as same as each other and all these were not formed the unity,lacking the basis foundation especially in the study of animal model.We began with establishing TON model and apply the objective examination methods to provide references to the clinical for its mechanism , checking standard , diagnosis and therapy and prognosis. [Methods] 2 rabbits and 2 cats who were health and growned up were killed.Whose nasal cavity, sinus and optic nerve were observed.Domestic cat was the ideal experiment animal.8 cats who were health and growned up were selected.The right eyes were selected as the experiment eyes and the left eyes were selected as the control's.Pattern Visual Evoked Potential(PR-VEP)was examined before damage.Through the nasal cavity sieve and sphenoid sinus,optic nerve of the pipeline was damaged by the injury tool which was made by
ourselves.And animal models of TON were established,the PR-VEP was examined again by which we determined the succeed model.PR-VEP were examined at1h. 1d, 3d, 1w, 2w, 4w after damage.
[Results] The paranasal sinus construction and optic nerve of the cat resembled with mankind,the nerve tube was completely and cat was the ideal experiment animal.8 cats's N75P100, P100N145 amplitude reduced and N75 , P100, N145 peak time prolong at 1h, 1d, 3d, 1w after damage. The N75 P100'S, P100N145's average amplitude respectively were 8.60 1.32uv, 7.90 0.39uv, 6.82 1.22uv, 3.40 0.43uv and 6.00 2.45uv, 4.50 0.93uv, 6.60 0.54uv, 3.00 0.91uv.The N75's, P100'S, N145'S average peak time resp-ecttively were 82.80+0.69ms, 120.60+1.36ms, 174.00 2.94ms, 106.20+7.14 ms, 136.80 6.17ms , 178.20 7.28ms,101.40 5.68ms , 144.60 7.28ms , 191.40 11.34ms,106.80 11.93ms, 148.80 14.21ms, 202.80 14.40ms.2w's and 4w's PR-VEP waves respectively were smooth threads.PR-VEP before operation comparing to 1h, 1d, 3d, 1w after operation were P<0.05, P<0.05, P,0.05, P<0.05 . PR-VEP of 1h comparing to 1d, 3d, 1w were P<0.05,1d, 3d, 1w compared each other were P>.05 or P<0.05.
[Conclusion]This animal model was similar to clinical optic nerve decompression through nasal cavity , sieve and sphenoid sinus.The change of PR-VEP was distinctively before damage and after damage.This showed that this model was successful.And the PR-VEP of different time was different after damage.This was correlated with the effect which was caused by optic nerve decompression operation after injury in different time.The pupil reflects to the light was not proper examination standerd for TON animal model establish the success or not.
方法 选择健康成年家兔2只、家猫2只，处死后解剖观察鼻腔鼻窦及视神经的解剖关系，确定家猫为实验动物。选择健康成年家猫8只，以自身左眼为实验眼，右眼为对照眼，术前检测视觉诱发电位(VISUAL EVOKED POTENTIAL，VEP)。经鼻腔筛蝶窦入路，用自制视神经管损伤器损伤管内段视神经，建立TON模型，检测图形视觉诱发电位(PR-VEP)，观察动物瞳孔对光反应。以PR-VEP波形改变为模型建立成功检测的指标。观察动物分别在术后1h、1d、3d、1w、2w、4w时的PR-VEP波形和瞳孔变化。
结果 家猫的鼻窦结构与视神经走行与人类相似，有完整的视神经管，为较适合的实验动物。内镜下经鼻腔鼻窦入路寻找视神经管方法可行。8只猫损伤后有4只瞳孔不同程度散大，直接对光反应减弱或消失，间接对光反应灵敏，但有4只家猫的瞳孔对光反应双侧无明显差异。PR-VEP中N_(75)P_(100)、P_(100)N_(145)波幅均减小，N_(75)、P_(100)、N_(145)峰潜时均延长。损伤后1h、1d、3d、1w时的N_(75)P_(100)、P_(100)N_(145)波幅分别平均为8.60±1.32uv、7.90±0.39uv；6.81±1.22uv、3.40±0.43uv；6.00±2.07uv、4.50±0.78uv；6.60±1.62uv、3.00±0.78uv。N_(75)、P_(100)、N_(145)各峰潜时分别平均为82.80±0.69ms、120.60±1.36ms、174.00±2.94ms；106.30±7.14ms、136.80±6.17ms、178.20±7.28ms；101.40±5.68ms、144.60±6.16ms、191.40±9.59ms；106.80±10.08ms、148.80±12.02ms、202.80±12.16ms。损伤后2w与4w时PR-VEP的波形引出为一条近似直线，无法测出各波幅及各峰潜时的数值。损伤前与损伤后1h、1d、3d、1w PR-VEP比较为P＜0.05；1h与1d、3d、1w比较P值＜0.05，1d、3d、1w之间两两比较P值＞0.05或＜0.05。
结论 ①家猫的鼻窦结构与视神经走行与人类相似，有完整的视神经管，为较适合的实验动物。②内镜下经鼻腔筛蝶窦入路建立视神经损伤动物模型方法可行；
第一章中文摘要
③视神经管损伤前、后的VEP改变明显，VEP变化可作为外伤性视神经病动物模型的
客观监测指标;瞳孔对光反射不宜作为TON动物模型建立成功与否的检测指标
[Objective] Traumatic Optic Neuropathy(TON) was increasing with the traffic accident. The methods of diagnosis and therapy were variable,the consents and the results were not as same as each other and all these were not formed the unity,lacking the basis foundation especially in the study of animal model.We began with establishing TON model and apply the objective examination methods to provide references to the clinical for its mechanism , checking standard , diagnosis and therapy and prognosis. [Methods] 2 rabbits and 2 cats who were health and growned up were killed.Whose nasal cavity, sinus and optic nerve were observed.Domestic cat was the ideal experiment animal.8 cats who were health and growned up were selected.The right eyes were selected as the experiment eyes and the left eyes were selected as the control's.Pattern Visual Evoked Potential(PR-VEP)was examined before damage.Through the nasal cavity sieve and sphenoid sinus,optic nerve of the pipeline was damaged by the injury tool which was made by
ourselves.And animal models of TON were established,the PR-VEP was examined again by which we determined the succeed model.PR-VEP were examined at1h. 1d, 3d, 1w, 2w, 4w after damage.
[Results] The paranasal sinus construction and optic nerve of the cat resembled with mankind,the nerve tube was completely and cat was the ideal experiment animal.8 cats's N75P100, P100N145 amplitude reduced and N75 , P100, N145 peak time prolong at 1h, 1d, 3d, 1w after damage. The N75 P100'S, P100N145's average amplitude respectively were 8.60 1.32uv, 7.90 0.39uv, 6.82 1.22uv, 3.40 0.43uv and 6.00 2.45uv, 4.50 0.93uv, 6.60 0.54uv, 3.00 0.91uv.The N75's, P100'S, N145'S average peak time resp-ecttively were 82.80+0.69ms, 120.60+1.36ms, 174.00 2.94ms, 106.20+7.14 ms, 136.80 6.17ms , 178.20 7.28ms,101.40 5.68ms , 144.60 7.28ms , 191.40 11.34ms,106.80 11.93ms, 148.80 14.21ms, 202.80 14.40ms.2w's and 4w's PR-VEP waves respectively were smooth threads.PR-VEP before operation comparing to 1h, 1d, 3d, 1w after operation were P<0.05, P<0.05, P,0.05, P<0.05 . PR-VEP of 1h comparing to 1d, 3d, 1w were P<0.05,1d, 3d, 1w compared each other were P>.05 or P<0.05.
[Conclusion]This animal model was similar to clinical optic nerve decompression through nasal cavity , sieve and sphenoid sinus.The change of PR-VEP was distinctively before damage and after damage.This showed that this model was successful.And the PR-VEP of different time was different after damage.This was correlated with the effect which was caused by optic nerve decompression operation after injury in different time.The pupil reflects to the light was not proper examination standerd for TON animal model establish the success or not.
引文
1 Fukado Y. The therapy of the optic nerve injury. Mod Prob Ophthalmol: 1975:14:474-481
2 Fujitani T, Pring HP. Traumatic optic neuropathy and optic nerve decompression JPN J Ophthalmol, 1986;30:125-134
3 张天明，傅继弟，宋维贤等．经颅视神经管减压开放术．中华神经外科杂志．1999，15：97-98
4 宋维贤．管内段视神经损伤．全国眼科主治医生学习班讲义．中华医学会北京分会，1997．13
5 樊兆民，樊忠．国外医学耳鼻咽喉科分册，2001；25：80-83
6 魏文斌，张晓峰，方严，主编．当代临床眼科进展．合肥：安徽科学技术出版社，1998．399
7 Spoor TC, Hartel WC, lensink DB, etal. Treament of traumatic optic neuropathy with corticosteroids. Am J Ophthalmol, 1990,110:665.
8 蔡莉，惠延年，马吉献等．乳兔雪旺细胞对成兔视神经挫伤修复的作用．中华眼底病杂志，2000；16：91-93
9 姜荔，马志中，陶海等．兔视神经间接损伤的视神经组织压观察．中华创伤杂志，2000；16：238-240
10 刘杰，马志中，梁延杰．兔视神经间接损伤病理学观察．中华眼科杂志，1999；35：437-439
11 Jonas JB , Hayres SS. Optic disc morphology in experimental central retinal artery occlusion in rhesus[J].Am J Ophthalmol, 1999,127(5):523
12 Anderson DR. Traumatic optic neuropathy. Ann J Ophthalmol, 1973; 76:693--711
13 Cho ESKF. Analysis of the traumatic optic neuropathy effect. Exp Brain Res, 1989;78:567-574
14 Hasegawa M, Crompton MR. Animal model of traumatic optic neuropathy. Brain Res, 1988;452:345-357
15 Stevenson JA. Braugh JK: Analysis of crush damage on optic nerve. Exp Neurol. 1987;97:77-87
16 Yucel YH, Kalichman MW, Mizisin AP, et al. Histomophomertic analysis of optic nerve change in experimental glaucoma[J]. J Glaucoma, 1999,8 (1): 38
17 Li KK, Teknas TN, Lai A, et al. Traumatic optic neuropathy: result in 45 consecutive surgically treated patients. Otolaryngol Head Neck Surg, 1999;120:5
18 Cook MW, Levin LA, Joseph MP, etal. Traumatic optic neuropathy: A Meta-analysis. Arch Otolaryngol Head Neck Surg, 1996;122:389
19 胡爱莲，孙葆沈，董冬生等。碱性成纤维生长因子对大鼠视神经损伤的保护作用[J]。眼科新进展，2000；20：112-114
20 Morawwetz RB, Klin LB. Indirect injury of the optic nerve. Neurosurgery, 1984;14:755
21 Lessel S. Indirect optic nerve traum. Arch Ophthalmol, 1989, 107:382
22 Hayrsh ss. Posterior ischemic optic neuropathy, 1981,182:29-41
23 常青(综述)．外伤性视神经病变．中国眼耳鼻喉科杂志，1997，2：193-194
24 Feist RM, Kline LB, Lan BD et al. Therapy of traumatic optic neuropathy Ophthalmology, 1987;94:1567-1569
25 原田康夫．视神经管开放术．耳科临床，1995；78：1871-1874
26 Edmund J,Godtfredson E. Marcus-Gunn's tutor reflection. Acta Ophthalmol, 1963; 41:693-697
27 Levatin P. Traumatic optic neuropathy. Arch Ophthalmol, 1959;62:768-779
28 Kestenbaumm a. Clinical Methods of Neuro-Ophthalmologic Examination. New York, Grune and Straton, 1961, pp 344-357
29 Hughes B. Optic nerve injury. Bull Jhons Hopkins Hosp, 1962;111:98-126
30 Ramsay JH. Optic nerve, injury in fracture of the canal. Br J Ophthalmol, 1979;63:607-610
31 Head injury nomenclature. Clin Neurosurg, 1966;12:388-394
32 Walsh FB.In Freeman HM(ed);Ocular Trauma. New York, Appelton-Cen-Tury-Crofts, 1979, ch 35, pp 335-351
33 Pringle JH. Br Med J,1922;2:1156-1157
34 Turner JWA. Brain 1943;66:140-151
35 Niho S et al. Am J Ophalmol, 1961;51:659-665
36 Hammer VG, Ambos SR. Surgical treatment of progressive visual loss in traumatic optic neuropathy.
37 Bodian M. Posterior ischemic optic neuropathy. NY State J Med, 1964; 64:916-920
38 Traquair HM,Hayrsh SS. Indirect optic nerve trauma. Brain, 1935; 58: 398-411.
39 Mahapatra AK, Bhatia r. Predictive value of vieual evoked potentials in unilateral optic nerve injury. Surg Neurol, 1989,31:339-342
40 Klin LB, Morawwetz RB. Indirect injury of the optic nerve. Neurosurger-y, 1984;14:755
41 Hooper RS. Optic nerve injury. Br J Surg, 1951;39:126-138 Head injury nomenclature. Clin Neurosurg, 1966;12:388-394
42 Imachi J,Walsh FB. Decompression of optic nerve injury and trauma of optic nerve. Jpn J Ophthalmol, 1968;12:70-85
43 Kennerdell JS, Amshaugh GA, Myers EN. Transantral-Ethmoidal decompression of optic canal fracture. Arch Ophthalmol, 1976;94-15
44 Obenchain TG. High dose corticosteroids for treatment of vision loss due to indirect injury to the optic nerve. Bull Los Angrles Neurol Soc, 1973; 38:13-20
45 Klin Monatsbl Augenheilkd, 1971;159:818-819
2 Fujitani T, Pring HP. Traumatic optic neuropathy and optic nerve decompression JPN J Ophthalmol, 1986;30:125-134
3 张天明，傅继弟，宋维贤等．经颅视神经管减压开放术．中华神经外科杂志．1999，15：97-98
4 宋维贤．管内段视神经损伤．全国眼科主治医生学习班讲义．中华医学会北京分会，1997．13
5 樊兆民，樊忠．国外医学耳鼻咽喉科分册，2001；25：80-83
6 魏文斌，张晓峰，方严，主编．当代临床眼科进展．合肥：安徽科学技术出版社，1998．399
7 Spoor TC, Hartel WC, lensink DB, etal. Treament of traumatic optic neuropathy with corticosteroids. Am J Ophthalmol, 1990,110:665.
8 蔡莉，惠延年，马吉献等．乳兔雪旺细胞对成兔视神经挫伤修复的作用．中华眼底病杂志，2000；16：91-93
9 姜荔，马志中，陶海等．兔视神经间接损伤的视神经组织压观察．中华创伤杂志，2000；16：238-240
10 刘杰，马志中，梁延杰．兔视神经间接损伤病理学观察．中华眼科杂志，1999；35：437-439
11 Jonas JB , Hayres SS. Optic disc morphology in experimental central retinal artery occlusion in rhesus[J].Am J Ophthalmol, 1999,127(5):523
12 Anderson DR. Traumatic optic neuropathy. Ann J Ophthalmol, 1973; 76:693--711
13 Cho ESKF. Analysis of the traumatic optic neuropathy effect. Exp Brain Res, 1989;78:567-574
14 Hasegawa M, Crompton MR. Animal model of traumatic optic neuropathy. Brain Res, 1988;452:345-357
15 Stevenson JA. Braugh JK: Analysis of crush damage on optic nerve. Exp Neurol. 1987;97:77-87
16 Yucel YH, Kalichman MW, Mizisin AP, et al. Histomophomertic analysis of optic nerve change in experimental glaucoma[J]. J Glaucoma, 1999,8 (1): 38
17 Li KK, Teknas TN, Lai A, et al. Traumatic optic neuropathy: result in 45 consecutive surgically treated patients. Otolaryngol Head Neck Surg, 1999;120:5
18 Cook MW, Levin LA, Joseph MP, etal. Traumatic optic neuropathy: A Meta-analysis. Arch Otolaryngol Head Neck Surg, 1996;122:389
19 胡爱莲，孙葆沈，董冬生等。碱性成纤维生长因子对大鼠视神经损伤的保护作用[J]。眼科新进展，2000；20：112-114
20 Morawwetz RB, Klin LB. Indirect injury of the optic nerve. Neurosurgery, 1984;14:755
21 Lessel S. Indirect optic nerve traum. Arch Ophthalmol, 1989, 107:382
22 Hayrsh ss. Posterior ischemic optic neuropathy, 1981,182:29-41
23 常青(综述)．外伤性视神经病变．中国眼耳鼻喉科杂志，1997，2：193-194
24 Feist RM, Kline LB, Lan BD et al. Therapy of traumatic optic neuropathy Ophthalmology, 1987;94:1567-1569
25 原田康夫．视神经管开放术．耳科临床，1995；78：1871-1874
26 Edmund J,Godtfredson E. Marcus-Gunn's tutor reflection. Acta Ophthalmol, 1963; 41:693-697
27 Levatin P. Traumatic optic neuropathy. Arch Ophthalmol, 1959;62:768-779
28 Kestenbaumm a. Clinical Methods of Neuro-Ophthalmologic Examination. New York, Grune and Straton, 1961, pp 344-357
29 Hughes B. Optic nerve injury. Bull Jhons Hopkins Hosp, 1962;111:98-126
30 Ramsay JH. Optic nerve, injury in fracture of the canal. Br J Ophthalmol, 1979;63:607-610
31 Head injury nomenclature. Clin Neurosurg, 1966;12:388-394
32 Walsh FB.In Freeman HM(ed);Ocular Trauma. New York, Appelton-Cen-Tury-Crofts, 1979, ch 35, pp 335-351
33 Pringle JH. Br Med J,1922;2:1156-1157
34 Turner JWA. Brain 1943;66:140-151
35 Niho S et al. Am J Ophalmol, 1961;51:659-665
36 Hammer VG, Ambos SR. Surgical treatment of progressive visual loss in traumatic optic neuropathy.
37 Bodian M. Posterior ischemic optic neuropathy. NY State J Med, 1964; 64:916-920
38 Traquair HM,Hayrsh SS. Indirect optic nerve trauma. Brain, 1935; 58: 398-411.
39 Mahapatra AK, Bhatia r. Predictive value of vieual evoked potentials in unilateral optic nerve injury. Surg Neurol, 1989,31:339-342
40 Klin LB, Morawwetz RB. Indirect injury of the optic nerve. Neurosurger-y, 1984;14:755
41 Hooper RS. Optic nerve injury. Br J Surg, 1951;39:126-138 Head injury nomenclature. Clin Neurosurg, 1966;12:388-394
42 Imachi J,Walsh FB. Decompression of optic nerve injury and trauma of optic nerve. Jpn J Ophthalmol, 1968;12:70-85
43 Kennerdell JS, Amshaugh GA, Myers EN. Transantral-Ethmoidal decompression of optic canal fracture. Arch Ophthalmol, 1976;94-15
44 Obenchain TG. High dose corticosteroids for treatment of vision loss due to indirect injury to the optic nerve. Bull Los Angrles Neurol Soc, 1973; 38:13-20
45 Klin Monatsbl Augenheilkd, 1971;159:818-819