神经生长因子在糖尿病大鼠视网膜神经节细胞凋亡中的作用机制

doi:10.3969/j.issn.1671-7171.2025.11.003

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摘要 【目的】探讨神经生长因子(NGF)在糖尿病(DM)大鼠视网膜神经节细胞(RGCs)凋亡中的作用机制。【方法】24只大鼠随机分成四组,每组6只。正常对照组(NC组):大鼠未做处理;DM模型组(DM组):采用链脲佐菌素(STZ)一次性腹腔注射诱导建立DM模型;实验对照组[DM+腺病毒相关载体(AAV)组]):造模成功后,玻璃体腔注射AAV+绿色荧光蛋白(GFP);实验干预组(DM+AAV-NGF组):造模成功后,玻璃体腔注射AAV+NGF。采用视网膜电图(ERG)测定各组b波振幅,观察各组视网膜组织切片荧光染色,检测并比较各组NGF、TrkA、P75、AKT、PI3K、Bax、Caspase3蛋白表达量和mRNA表达量。【结果】DM组b波振幅低于NC组, DM+AAV-NGF组b波振幅高于DM组,差异均有统计学意义(P<0.05)。各组大鼠NGF、TrkA、P75、AKT、PI3K、Bax、Caspase3蛋白表达量和mRNA表达量比较,差异均有统计学意义(P<0.05);各组大鼠PI3K蛋白表达量和mRNA表达量比较,差异无统计学意义(P>0.05)。【结论】玻璃体腔注射AAV+NGF,可抑制早期DM大鼠RGCs的凋亡,改善早期DM大鼠的视网膜功能,其可能机制是激活了TrkA/P75受体,从而激活PI3K/Akt 通路,下调Bax、Caspase3的表达水平。

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	李东慧
	杨卓
	王启常

关键词 ：大鼠, 糖尿病,实验性, 神经生长因子, 视网膜神经节细胞, 细胞凋亡

Abstract：【Objective】To explore the mechanism of nerve growth factor (NGF) in the apoptosis of retinal ganglion cells (RGCs) in diabetic rats. 【Methods】 Twenty-four rats were randomly divided into 4 groups, with 6 rats in each group. Normal control group (the NC group): Rats were not treated; Diabetic model group (the DM group): Rats were injected intraperitoneally with streptozotocin (STZ) to establish a DM model; Experimental control group [the DM + adeno-associated virus (AAV) group]: After successfully established DM modeling, AAV + green fluorescent protein (GFP) was injected into the vitreous cavity; Experimental intervention group (the DM + AAV-NGF group): After DM modeling successfully established, AAV + NGF was injected into the vitreous cavity. The b-wave amplitude of each group was measured by electroretinogram (ERG), and the fluorescence staining of retinal tissue sections was observed. The expression levels of NGF, TrkA, P75, AKT, PI3K, Bax, and Caspase3 proteins and mRNAs in each group were detected and compared. 【Results】 The b-wave amplitude in the DM group was lower than that in the NC group, and the b-wave amplitude in the DM + AAV-NGF group was higher than that in the DM group, with statistically significant differences (P<0.05). There were statistically significant differences in the expression levels of NGF, TrkA, P75, AKT, Bax, and Caspase3 proteins and mRNAs among the groups (P<0.05). However, there were no statistically significant differences in the expression levels of PI3K protein and mRNA among the groups (P>0.05). 【Conclusion】 Intravitreal injection of AAV + NGF can inhibit the apoptosis of RGCs in early diabetic rats and improve the retinal function of diabetic rats. The possible mechanism is that it activates the TrkA/P75 receptor, thereby activating the PI3K/Akt pathway and down-regulating the expression levels of Bax and Caspase3.

Key words： Rats Diabetes Mellitus, Experimental Nerve Growth Factor Retinal Ganglion Cells Apoptosis

收稿日期: 2025-08-11

中图分类号:

R587.1

基金资助:湖南省自然科学基金(2023JJ70042);爱尔眼科集团项目基金(AM2001D3)

通讯作者: **E-mail:wqc1115@sina.com

引用本文:

李东慧, 杨卓, 王启常. 神经生长因子在糖尿病大鼠视网膜神经节细胞凋亡中的作用机制[J]. 医学临床研究, 2025, 42(11): 1849-1852.
LI Donghui, YANG Zhuo, WANG Qichang. Mechanism of Nerve Growth Factor in Retinal Ganglion Cell Apoptosis in Diabetic Rats. JOURNAL OF CLINICAL RESEARCH, 2025, 42(11): 1849-1852.

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http://journal07.magtech.org.cn/yxlcyj/CN/10.3969/j.issn.1671-7171.2025.11.003 或 http://journal07.magtech.org.cn/yxlcyj/CN/Y2025/V42/I11/1849

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