中药复方VIS抑制急性高眼压大鼠视网膜神经节细胞凋亡机制  

The mechanism of VIS a compound of Chinese herb extracts inhibits RGCs apoptosis in a rat acute intraocular hypertension model

作　　者：尹朔 刘立夏[2] 冀璐[1] 王中峰[3] 路雪婧[1] 

机构地区：[1]成都中医药大学,四川成都610075 [2]河南护理职业学院,河南安阳455001 [3]复旦大学脑科学研究院,中国上海200032

出　　处：《中医眼耳鼻喉杂志》2015年第1期11-15,共5页Journal of Chinese Ophthalmology and Otorhinolaryngology

基　　金：国家重大科技专项（2009ZX09103-369）;教育部科学技术研究重点项目（2010188）;四川省学术技术带头人培养基金

摘　　要：目的研究中药复方VIS的不同配比对急性高眼压大鼠视网膜凋亡相关蛋白Bcl-2／Bax表达的影响，以及最佳配比复方VIS对视网膜神经节细胞外向钾电流的调控，探讨其视神经保护的可能机制。方法利用前房灌注生理盐水的方法急性升高大鼠眼内压，接着使用不同配比的VIS及LBP、DSX、阳性对照药物灌胃7d，利用免疫组化方法检测凋亡相关基因的表达。接着选取最佳配比的复方VIS，采用全细胞膜片钳技术观察其对急性高眼压大鼠RGC的电压门控外向钾电流的影响。将细胞膜电位钳制在-70mV，然后给予一系列400ms的去极化脉冲，以10mV的递增使细胞去极化到＋20mV，从而诱导出外向钾电流。结果前房急性灌注生理盐水7d造成视网膜凋亡相关基因Bcl-2／Bax比值的下调，不同配比的VIS呈不同程度地下调促凋亡基因Bax，促进凋亡抑制基因Bcl-2的表达，因而提高Bcl-2／Bax比值；复方VIS8具有抑制或降低急性高眼压损伤后RGC的外向钾电流的电流幅度下调的作用。结论急性眼内压升高引起视网膜内在凋亡途径的启动，中药复方VIS能够有效地抑制神经节细胞的凋亡，其中VIS8作用显著，且具有抑制或降低急性高眼压损伤后RGC的外向钾电流幅度下调的作用。这可能是中药复方VIS抑制急性高眼压RGC凋亡，从而保护视神经及RGC的机制之一。Objective To investigate the effect of VIS, a Chinese herbal compound, on the expression of Bcl-2/Bax, two apoptosis related proteins, in rat retina with acute ocular hypertension, and the effect of the best group of VIS on RGC outward K^＋ current, thereby exploring the possible mechanisms of VIS on optic nerve protection. Methods Rat acute ocular hypertension model was reproduced by anterior chamber perfusion with normal saline for 60 minutes. VIS was administered by a method of gavage for 7 days consecutively. Expression of Bcl-2/Bax was examined by using immunohistochemistry method. Outward pothssium channel currents were recorded by using whole-cell patch-clamp techniques on acutely isolated RGCs. Outward K^＋ currents were induced by a series of depolarizing voltage pulses from a holding potential of -70 mV to ＋20 mV in an increment of 10 mV. Results The ratio Bcl-2/Bax was decreased at 7th day after elevation of intraocular pressure, which was reversed by VIS, the best one is VIS8. VIS8 rescured acute ocular hypertension-induced changes of outward potassium currents in RGCs. Conclusion These results suggest that acute elevation of intraocular pressure triggers retinal intrinsic apoptotic pathway, and the traditional Chinese medicine compound VIS can effectively inhibit apoptosis of retinal ganglion cells. VIS8 provides a protective effect against RGC damage in the rat acute intraocular hypertension model, which may be mediated by stabilizing the outward potassium currents.

关 键 词：急性高眼压 中药复方VIS RGCS Bcl-2/Bax 钾电流 

分 类 号：R774[医药卫生—眼科]