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[摘要]
目的: 研究睫状神经营养因子(ciliary neurontrophic factor, CNTF)对糖尿病早期大鼠视网膜神经组织的保护作用。
方法:选择40只健康成年雄性SD大鼠(250g-280g)一次性腹腔注射链脲佐菌素(Streptozotin ,STZ)60mg/kg 诱发糖尿病模型(DM),将DM大鼠随机分组为DM+CNTF组和DM+BSS组。DM+CNTF组给予玻璃体腔内注射CNTF(1.0μg /2μL),DM+BSS组注射BSS液(2μL)。分别观测0、4 、8、12wk两组大鼠体质量和血糖变化,于4wk和12wk进行原位细胞调亡(TUNEL法)的检测及视网膜神经组织超微结构的观察。
结果:DM+CNTF组大鼠的血糖和体质量与DM+BSS组比较无显著性差异(P>0.05)。12wk时TUNEL检测DM+CNTF组大鼠神经节细胞凋亡与DM+BSS组相比减少(P<0.05)。透射电镜下观察发现从4wk起两组大鼠视网膜神经组织出现细胞凋亡的改变,经CNTF治疗细胞凋亡改变有所减轻,表现为外节膜盘间隙减小,感光细胞水肿减轻及核染色质浓集减轻等。
结论: CNTF对DM+CNTF组和DM+BSS组大鼠的体重及血糖无明显影响。CNTF治疗组结果显示对本实验糖尿病大鼠视网膜神经节细胞及感光细胞有一定保护作用。
[Key word]
[Abstract]
AIM: To evaluate the protective effects of ciliary neurotrophic factor(CNTF)against retinal neurons damage in a rat model of diabetes mellitus(DM).
METHODS: Forty Sprague Dawley rats(weighing 250g-280g)received an intraperitoneal injection of streptozotocin(60mg/kg). The rats were then randomly divided into two groups: the treatment(DM+CNTF)or control(DM+BSS)group. The CNTF(0.5μg/μL)or balanced salt solution(2μL)was injected into the vitreus of the rats. Apoptosis of retinal ganglion cells(RGCs)was measured and retinal ultrastructure was assessed 4 and 12 weeks after establishing the model and performing the injections.
RESULTS: No difference in blood glucose or body weight was noted between the two groups. There were significantly fewer apoptotic RGCs in DM+CNTF group(8.56±1.22, P<0.05). From week 4, the neurons in the two groups of rats had degenerative changes(i.e., shrunken membrane disk spaces, swollen photoreceptor nuclei, and chromatin condensation)were noted on transmission electron microscopy. In DM+CNTF group, these abnormalities were improved by week 12.
CONCLUSION: CNTF has no significant effects on blood glucose levels or body weight in either group. CNTF shows protective effects on RGCs and photoreceptors based on apoptosis and transmission electron microscopy. Additional studies to establish the optimal time of administration and dosage of neurotrophic factors to achieve the greatest protective effects on retinal nerve tissue are warranted.
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