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雷公藤甲素对慢性青光眼大鼠模型视网膜神经节细胞的保护作用

Protective effects of triptolide on retinal ganglion cells in a rat model of chronic glaucoma.

作者信息

Yang Fan, Wang Dongmei, Wu Lingling, Li Ying

机构信息

Ophthalmology Department, Peking University Third Hospital, Beijing, People's Republic of China.

出版信息

Drug Des Devel Ther. 2015 Nov 16;9:6095-107. doi: 10.2147/DDDT.S92022. eCollection 2015.

DOI:10.2147/DDDT.S92022
PMID:26604697
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4655911/
Abstract

PURPOSE

To study the effects of triptolide, a Chinese herb extract, on retinal ganglion cells (RGCs) in a rat model of chronic glaucoma.

METHODS

Eighty Wistar rats were randomly divided into triptolide group (n=40) and normal saline (NS) group (n=40). Angle photocoagulation was used to establish the model of glaucoma, with right eye as laser treated eye and left eye as control eye. Triptolide group received triptolide intraperitoneally daily, while NS group received NS. Intraocular pressure (IOP), anti-CD11b immunofluorescent stain in retina and optic nerve, RGCs count with Nissel stain and microglia count with anti-CD11b immunofluorescence stain in retina flat mounts, retinal tumor necrosis factor (TNF)-α mRNA detection by reverse transcription-polymerase chain reaction, and double immunofluorescent labeling with anti-TNF-α and anti-CD11b in retinal frozen section were performed.

RESULTS

Mean IOP of the laser treated eyes significantly increased 3 weeks after photocoagulation (P<0.05), with no statistical difference between the two groups (P>0.05). RGCs survival in the laser treated eyes was significantly improved in the triptolide group than the NS group (P<0.05). Microglia count in superficial retina of the laser treated eyes was significantly less in the triptolide group (30.40±4.90) than the NS group (35.06±7.59) (P<0.05). TNF-α mRNA expression in the retina of the laser treated eyes in the triptolide group decreased by 60% compared with that in the NS group (P<0.01). The double immunofluorescent labeling showed that TNF-α was mainly distributed around the microglia.

CONCLUSION

Triptolide improved RGCs survival in this rat model of chronic glaucoma, which did not depend on IOP decrease but might be exerted by inhibiting microglia activities and reducing TNF-α secretion.

摘要

目的

研究中药提取物雷公藤甲素对慢性青光眼大鼠模型视网膜神经节细胞（RGCs）的影响。

方法

80只Wistar大鼠随机分为雷公藤甲素组（n = 40）和生理盐水（NS）组（n = 40）。采用房角光凝法建立青光眼模型，右眼为激光治疗眼，左眼为对照眼。雷公藤甲素组每日腹腔注射雷公藤甲素，NS组注射NS。检测眼压（IOP）、视网膜和视神经中抗CD11b免疫荧光染色、用尼氏染色法计数RGCs以及用抗CD11b免疫荧光染色法计数视网膜铺片中的小胶质细胞，通过逆转录-聚合酶链反应检测视网膜肿瘤坏死因子（TNF）-α mRNA，并在视网膜冰冻切片中进行抗TNF-α和抗CD11b双重免疫荧光标记。

结果

光凝后3周，激光治疗眼的平均眼压显著升高（P < 0.05），两组间无统计学差异（P > 0.05）。雷公藤甲素组激光治疗眼中RGCs的存活率显著高于NS组（P < 0.05）。雷公藤甲素组激光治疗眼视网膜浅层的小胶质细胞计数（30.40±4.90）明显少于NS组（35.06±7.59）（P < 0.05）。雷公藤甲素组激光治疗眼视网膜中TNF-α mRNA表达较NS组降低了60%（P < 0.01）。双重免疫荧光标记显示TNF-α主要分布在小胶质细胞周围。

结论

在该慢性青光眼大鼠模型中，雷公藤甲素可提高RGCs的存活率，其作用不依赖于眼压降低，可能是通过抑制小胶质细胞活性和减少TNF-α分泌来实现的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c178/4655911/03756ad8d748/dddt-9-6095Fig10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c178/4655911/b058618e3f4e/dddt-9-6095Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c178/4655911/ce6effc7acc3/dddt-9-6095Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c178/4655911/0aae1d3d0e38/dddt-9-6095Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c178/4655911/84c97e781cf9/dddt-9-6095Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c178/4655911/420210baf9ff/dddt-9-6095Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c178/4655911/77ec48f29ffb/dddt-9-6095Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c178/4655911/ca1755afc4a0/dddt-9-6095Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c178/4655911/e11fc457bb11/dddt-9-6095Fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c178/4655911/8b55a05955c8/dddt-9-6095Fig9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c178/4655911/03756ad8d748/dddt-9-6095Fig10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c178/4655911/b058618e3f4e/dddt-9-6095Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c178/4655911/ce6effc7acc3/dddt-9-6095Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c178/4655911/0aae1d3d0e38/dddt-9-6095Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c178/4655911/84c97e781cf9/dddt-9-6095Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c178/4655911/420210baf9ff/dddt-9-6095Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c178/4655911/77ec48f29ffb/dddt-9-6095Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c178/4655911/ca1755afc4a0/dddt-9-6095Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c178/4655911/e11fc457bb11/dddt-9-6095Fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c178/4655911/8b55a05955c8/dddt-9-6095Fig9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c178/4655911/03756ad8d748/dddt-9-6095Fig10.jpg

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