| 李兴钰,汤锦菲,李菲菲.藏红花酸调控EGR-1信号轴抑制近视小鼠巩膜重塑的作用机制研究[J].浙江中西医结合杂志,2025,35(5): |
| 藏红花酸调控EGR-1信号轴抑制近视小鼠巩膜重塑的作用机制研究 |
| The mechanism of crocetin regulating EGR-1 signal axis to inhibit scleral remodeling in myopic mice |
| 投稿时间：2024-10-14 修订日期：2025-02-23 |
| DOI： |
| 中文关键词: 近视 藏红花酸 早期生长反应因子-1 巩膜重塑 |
| 英文关键词:Myopia Crocetin Early growth response factor-1 Scleral remodeling |
| 基金项目:浙江省中医药科技计划项目(2022ZB117) |
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| 中文摘要: |
| 目的 通过观察藏红花酸对近视模型小鼠眼球组织中早期生长反应因子-1（the early growth responsive gene-1,EGR-1）信号轴相关基因表达及巩膜组织形态改变的影响，进一步探讨藏红花酸对近视进展防控的效果及其作用机制。方法 将36只3周龄C57BL/6小鼠分为低浓度藏红花酸组、高浓度藏红花酸组和生理盐水对照组，每组12只。所有小鼠均选择右眼建立近视模型。模型建立期间藏红花酸组每日藏红花酸灌胃，低浓度组每次给药5 mg/kg，高浓度组每次给药10 mg/kg，每日1次连续4周。期间对照组给予等量生理盐水灌胃。在小鼠3周龄、7周龄时，测量各组小鼠右眼屈光力、眼轴长度。7周龄处死小鼠对右眼眼球组织进行苏木精—伊红(hematoxylin-eosin, HE)染色，观察巩膜组织形态学改变，并且通过免疫组化和实时荧光定量多聚核苷酸链式反应(Quantitative Real-time polymerase chain reaction, QPCR)检测眼球组织中血管内皮生长因子（vascular endothelial growth factor, VEGF）、EGR-1、组织基质金属蛋白酶2（matrix metalloproteinase-2,MMP-2）的表达量。结果 HE染色发现高浓度藏红花酸组巩膜组织厚度依次高于低浓度组和对照组。高浓度藏红花酸组干预4周后相较对照组屈光力呈现更多远视偏移[(7.10±0.51) D比(5.67±0.58) D，P<0.01]，眼轴更短[(3.25±0.04) mm比(3.31±0.05) mm，P<0.05]，且差异具有统计学意义。低浓度干预组眼轴较对照组差异没有统计学意义[(3.28±0.08) mm比(3.31±0.05) mm，P>0.05]。与对照组比较，高浓度藏红花酸组EGR-1[(1.29±0.01)比(1.21±0.00), P<0.01]和VEGF[(1.27±0.01)比(1.25±0.00)，P<0.01]的mRNA表达量显著增高，MMP-2[(1.07±0.01)比(1.39±0.02)，P<0.01]显著降低。低浓度藏红花酸组VEGF的mRNA表达较对照组增高[（1.27±0.01）比(1.25±0.00)，P<0.01]，MMP-2显著降低[（1.29±0.01）比(1.39±0.02)，P<0.01]，EGR-1没有统计学差异[(1.22±0.00)比(1.21±0.00),P>0.05]。与对照组比较，高浓度藏红花酸组EGR-1[(0.24±0.01)比(0.20±0.04), P<0.05]和VEGF[(0.24±0.00)比(0.17±0.04), P<0.05]的蛋白表达量显著增高，MMP-2[(0.24±0.01)比(0.26±0.01),P<0.01]显著降低。低浓度藏红花酸组较对照组EGR-1[(0.23±0.02)比(0.20±0.04),P>0.05]、MMP-2 [(0.25±0.01)比(0.26±0.01),P>0.05]、VEGF[(0.20±0.04)比(0.17±0.04),P>0.05]蛋白表达量均无统计学差异。结论 藏红花酸通过激活EGR-1表达，下调MMP-2及上调VEGF来降低细胞外基质降解，最终发挥了抑制巩膜重塑的作用，抑制近视眼轴增长。 |
| 英文摘要: |
| Objective To observe the effects of crocetin on the expression of the early growth responsive gene-1（EGR-1）related gene in eyeball cells of myopic mice and the changes of scleral tissue morphology, the pathological mechanism and effect of crocetin on the prevention and control of myopia progression were further discussed. Methods Thirty-six 3-week-old C57BL/6 mice were divided into low-concentration crocetin group, high-concentration crocetin group and saline control group, with 12 mice in each group. All mice chose right eye to establish myopia model. During the establishment of the model, the crocetin group was given daily administration of crocetin, the low-concentration group was given 5 mg/kg each time, and the high-concentration group was given 10 mg/kg each time, once a day for 4 weeks. The control group was given the same amount of normal saline. The refractive power and axial length of the right eye were measured at the age of 3 weeks and 7 weeks. Hematoxylin-eosin（HE）staining was performed on the right eye tissue of 7-week-old mice to observe the scleral histopathological changes, and the expression levels of vascular endothelial growth factor （VEGF）, EGR-1, and matrix metalloproteinase-2（MMP-2）in the eye tissue were detected by immunohistochemistry and Quantitative Real-time polymerase chain reaction (QPCR). Results HE staining showed that scleral tissue thickness of high concentration group was higher than that of low concentration group and control group. After 4 weeks of intervention, the high-concentration group of crocetin showed higher presbyopic shift[(7.10±0.51) D vs. (5.67±0.58) D, P<0.01] and shorter eye axis [(3.25±0.04) mm vs. (3.31±0.05) mm, P<0.05] than the control group, the difference was statistically significant. There was no significant difference in ocular axis between the low concentration intervention group and the control group[(3.28±0.08) mm vs. (3.31±0.05) mm, P>0.05]. Compared with the control group, the mRNA expression levels of EGR-1 [(1.29±0.01) vs. (1.21±0.00), P<0.01]and VEGF[(1.27±0.01) vs. (1.25±0.00), P<0.01] were significantly increased, and MMP-2[(1.07±0.01) vs. (1.39±0.02), P<0.01] was significantly decreased in high concentration crocetin group. The mRNA expression of VEGF in low concentration crocetin group was higher than that in control group[（1.27±0.01） vs. (1.25±0.00), P<0.01], MMP-2 was significantly lower than that in control group [（1.29±0.01）vs. (1.39±0.02), P<0.01], and there was no statistical difference in EGR-1[(1.22±0.00) vs. (1.21±0.00), P>0.05]. Compared with the control group, the protein expression levels of EGR-1 [(0.24±0.01) vs. (0.20±0.04), P<0.05] and VEGF [(0.24±0.00) vs. (0.17±0.04), P<0.05] were significantly increased and MMP-2[(0.24±0.01) vs. (0.26±0.01), P<0.01] was significantly decreased in the high concentration crocetin group. There was no statistically significant difference in the protein expression levels of EGR-1[(0.23±0.02) vs. (0.20±0.04), P>0.05],MMP-2 [(0.25±0.01) vs. (0.26±0.01), P>0.05], VEGF[(0.20±0.04) vs. (0.17±0.04), P>0.05] in the low concentration crocetin group compared with the control group. Conclusion By activating the expression of EGR-1, crocetin down-regulates MMP-2 and increase VEGF to reduce the degradation of extracellular matrix, and finally plays a role in inhibiting scleral remodeling and inhibiting the axial growth of myopia. |
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