H-89和wortmannin对霍乱毒素促进受损视网膜节细胞再生作用的影响  

Effects of H-89 and Wortmannin on Promoting Effects of CTx onRegeneration of Injured Retinal Ganglion Cells

作　　者：李雯[1] 梁玉香[1] 李海标[1] 

机构地区：[1]中山大学基础医学院组织胚胎学教研室,广东广州510080

出　　处：《中山大学学报（医学科学版）》2005年第1期34-37,共4页Journal of Sun Yat-Sen University:Medical Sciences

基　　金：国家自然科学基金资助课题(39870266);广东省自然科学基金资助课题(980096)

摘　　要：【目的】研究蛋白激酶A(PKA)抑制剂H-89和磷酸肌醇3-激酶(PI3-K)特异抑制剂wortmannin对霍乱毒素(CTx)促进受损视网膜节细胞(RGCs)再生的影响,探讨CTx促进受损视网膜节细胞(RGCs)再生的作用机制。【方法】成年金黄地鼠近侧切断视神经(ON),移植一段自体坐骨神经(SN)与ON近侧残端缝接,玻璃体内注射给药。20只动物分4组,每组5只。注射CTx为CTx组,注射CTx和H-89为CTx+H组、注射CTx和wortmannin为CTx+W组、不给药组为对照组。用粒蓝(GB)逆行标记再生的RGCs,取视网膜于荧光镜下记数。【结果】动物存活4周后,对照组、CTx组和CTx+H组再生节细胞平均数(个/视网膜)分别为:(1431±352),(2567±883)和(1606±293)个/视网膜(n=5)。CTx+H组与对照组比较差异无显著性(P<0.05),而与CTx组比较有显著性差异(P<0.05),表明H-89可抑制CTx的促再生作用;CTx+W组再生节细胞数为:(1872±262)个/视网膜(n =5),与对照组和CTx组比较差异均有显著性(P <0.05),提示wortmannin对CTx有部分的抑制作用。【结论】CTx可能是通过PKA-CREB通路实现对受损RGCs的促再生作用,PI3-K-Akt通路可能是PKA-CREB通路的下游分支。To investigate the effects of PKA inhibitor H89 and PI3-K inhibitor wortmannin acting on the regeneration promoting effects of CTx and the regeneration promoting mechanism of CTx on injured retinal ganglion cells (RGCs). Optic nerve (ON) of adult golden hamster was transected, a segment of autologous sciatic nerve (SN) was removed and sutured to the proximal stump of ON. Twenty animals were separated into 4 groups, which were CTx, CTx+H, CTx+W, and control groups, each group have 5 animals. CTx only, CTx and H-89 or wortmannin were given by intravitreal injection. The regenerated RGCs were labeled retrogradely by granular blue (GB) and counted under fluorescent microscope. Four weeks later, the mean number of regenerating RGCs were counted as 1 431±352, 2 567±883, and 1 606±293/retina in control group, CTx group, and CTx + H group, respectively. The mean number of regenerating RGCs in the CTx +H group had no significant difference compared with that in control group (P < 0.05=, it has significant difference compared with that in CTxgroup (P < 0.05). This results showed that H-89 can inhibit the regeneration promoting effects of CTx on injured RGCs. In the group treated with wortmannin (CTx+W), the mean number of regenerating RGCs was 1 872±262/retina, which has significant difference compared with those in CTx group and control group (P < 0.05). This suggest that wortmannin can partially inhibit the regeneration promoting effects of CTx on injured RGCs. [Conclusion] The regeneration promoting effects of CTx on injured RGCs could be realized by activating PKA-CREB pathway, PI3-K-Akt pathway may be one of downstream pathways.

关 键 词：CT RGC 对照组 视网膜节细胞 霍乱毒素 注射 PI3-K PKA 动物 磷酸肌醇 

分 类 号：R774[医药卫生—眼科] R339[医药卫生—临床医学]