多聚物-1反应性T细胞对高眼压大鼠视网膜神经节细胞的保护机制  

Neuroprotection of retinal ganglion cells by T cells specific to copolymer-1 in rats with glaucoma

作　　者：李霞[1] 钱韶红[1] 孙兴怀[1] 

机构地区：[1]复旦大学附属眼耳鼻喉科医院眼科,上海200031

出　　处：《复旦学报（医学版）》2008年第3期358-362,368,共6页Fudan University Journal of Medical Sciences

基　　金：上海市科学技术委员会重点项目(04JC14023)

摘　　要：目的探讨多聚物-1(copolymer-1,Cop-1)反应性T细胞对高眼压大鼠视网膜神经节细胞(retinal ganglion cells,RGCs)的保护机制。方法大鼠后肢足垫注入0.2mg Cop-1或磷酸盐缓冲溶液(phosphate buff-ered solution,PBS)后10d,取出腹股沟淋巴结,培养Cop-1反应性T细胞(TCop-1)或PBS对照组T细胞(TPBS),用逆转录聚合酶链反应测定γ干扰素(interferon-gamma,γ-IFN)和IL-4mRNA的表达水平,从而分析培养的T细胞亚型;39只高眼压大鼠随机分为2组,1组(n=19)腹膜内注射TCop-1,另1组(n=20)注入TPBS作为对照,21d后观察RGCs的存活情况;用ELISA法测定T细胞上清液中脑源性神经营养因子(brain-derived neurotrophicfactor,BDNF)的分泌量。结果免疫后21d,Cop-1组RGCs存活数目较PBS组多(t=8.0204,P<0.01),TCop-1组gamma干扰素(interferon-gamma,γ-IFN)mRNA表达水平较PBS组高,而IL-4在两组间的表达差别无统计学意义。TCop-1在Cop-1刺激后脑源性神经营养因子分泌量为(3385.42±836.33)pg/mL,单纯TCop-1分泌量为(1026.24±135.10)pg/mL,而TPBS分泌量为(19.87±71.20)pg/mL。前者分泌量远大于后两者(F=175.66,P均<0.01,单因素方差分析和Bonferroi法)。结论Cop-1反应性Th1细胞是发挥视神经保护作用的重要细胞,保护机制之一可能通过TCop-1在局部分泌BDNF来实现。Objective To explore the mechanism of the neuroprotection of T cells specific to copolymer-1 （Cop-l）（TCop-1 ） in rat glaucoma model. Methods Ten days after 0. 2 mg Cop-1 or phosphate buffered solution（PBS）was injected into the rats＇ hind foot pads, their draining lymph nodes were surgically removed and Tcop-1 and Tees were respectively cultured. The mRNA of γ-IFN and IL-4 were analyzed by means of RT-PCR, through which the subtype of TCop-1 and Tees can be indicated. Thirty-nine rats with glaucoma were randomly divided into two groups. One group （n = 19） were injected with Tcop-1 intraperitoneally, the other group （n = 20） was injected with Tees. On 21st day after immunization, the number of retinal ganglion cells （RGCs） was calculated. The amount of brain-derived neurotrophic factor （BDNF） secreted by T cells was measured by using Sandwich ELISA kits. Results The mRNA level of γ-IFN expressed by Tcop-1 was higer than that expressed by Tees. The amount of BDNF secreted by Tcop-1 which was restimulated by Cop-1 ,TCOp-1 and TPBS was （3 385.42 ± 836. 33） pg/mL, （1 026. 24 ± 135.10） pg/mL and （19. 87 ± 71.20） pg/mL respectively. The former one was much higher than the latter two （F = 175.66, both P〈0. 01, One-way ANOVA and Bonferroi method）. Conclusions Thl specific to Cop-1 might play an important role in protecting RGCs in the rats with glaucoma. TCop-1 can secrete BDNF on the retina, which was at least one of the mechanisms of protection of RGCs.

关 键 词：青光眼 自身免疫 T细胞 脑源性神经营养因子 神经保护 

分 类 号：R774[医药卫生—眼科]