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[黄连素减轻小鼠慢性视网膜光损伤:P2X7R的作用及相关机制研究]

[Berberine Alleviates Chronic Retinal Light Damage in Mice: A Study of the Role of P2X7R and the Mechanisms Involved].

作者信息

Dai Leshu, Ye Shanshan, Song Zixuan, Song Jiantao

机构信息

( 100040) Eye Hospital, China Academy of Chinese Medical Sciences, Beijing 100040, China.

( 100007) Institute of Basic Theory of Traditional Chinese Medicine, China Academy of Chinese Medical Sciences, Beijing 100007, China.

出版信息

Sichuan Da Xue Xue Bao Yi Xue Ban. 2025 Jan 20;56(1):35-40. doi: 10.12182/20250160505.

DOI:10.12182/20250160505
PMID:40109457
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11914015/
Abstract

OBJECTIVE

To investigate the trend of dynamic changes and the mechanisms of P2X7R by which berberine (BBR) alleviates chronic retinal light injury in mice.

METHODS

A total of 90 mice were randomly divided into three groups, a blank control group ( = 10), a group exposed to low-intensity blue light (500 lux) for 12 hours per day for a duration of 3 months, which was referred to as the LD group ( = 40), and another group given BBR at a dose of 200 mg/kg via gastric gavage on top of the blue light exposure for the LD group, which was referred to as the LD + BBR group ( = 40). After the light exposure and gavage were completed, eye tissues were collected from the mice. Hematoxylin and eosin (HE) staining was performed to observe the protective effects of berberine on chronic retinal light damage in mice. TUNEL assay was performed to assess the effect of berberine on apoptotic cells in mice with chronic retinal light injury. Additionally, quantitative polymerase chain reaction (QPCR) was performed to assess the expression level of P2X7 receptors in chronic retinal light injury relieved by BBR.

RESULTS

Compared with the blank control group, the LD group exhibited abnormal retinal morphology, with some ganglion cells displaying reduced nuclei, a deeper stain, and loose arrangement. In the LD group, the cells in the inner nuclear layer appeared to be slightly more loosely arranged, while the cells in the outer nuclear layer cells were arranged in a disorderly way. Furthermore, the thickness of the outer nuclear layer of the retina from mice in the LD group was (47.11 ± 2.01) μm, and a significant number of apoptotic cells were observed in the outer nuclear layer, resulting in an apoptosis rate of (71.16 ± 5.99)% ( < 0.05). In contrast, the LD + BBR group showed mild abnormal retinal morphology with loosely arranged ganglion cells. In the LD + BBR group, the cells in both inner and outer nuclear layers of retina exhibited relatively intact morphology, uniform staining pattern, and tight arrangement. Moreover, the thickness measurement for outer nuclear layer revealed a value of (54.07 ± 2.05) μm, and there were only a few apoptotic cells present, resulting in an apoptotic rate of (16.02 ± 2.68)% ( < 0.05). Compared with that of the blank control group, the relative expression of mRNA in the retinas of the LD group was upregulated, with the difference between the two groups being statistically significant ( < 0.05). The relative expression of mRNA in the retinas of the LD + BBR group was downregulated, showing no statistical significance compared with that of the blank control group. However, compared with that of the LD group, the relative expression of mRNA in the retinas of the LD + BBR group showed a significant downward trend, and the difference between the two groups was statistically significant ( < 0.05).

CONCLUSION

Berberine can alleviate chronic retinal photodamage in mice, and inhibit the activation of P2X7R, thereby preventing the formation of retinal photodamage.

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f19/11914015/6c8f15f39aa2/scdxxbyxb-56-1-35-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f19/11914015/a9f1e3f87bed/scdxxbyxb-56-1-35-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f19/11914015/6c8f15f39aa2/scdxxbyxb-56-1-35-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f19/11914015/a9f1e3f87bed/scdxxbyxb-56-1-35-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f19/11914015/6c8f15f39aa2/scdxxbyxb-56-1-35-2.jpg
摘要

目的

探讨小檗碱(BBR)减轻小鼠慢性视网膜光损伤的动态变化趋势及P2X7R机制。

方法

将90只小鼠随机分为三组,空白对照组(n = 10),每天暴露于低强度蓝光(500勒克斯)12小时,持续3个月的组,称为LD组(n = 40),另一组在LD组蓝光暴露基础上,通过胃管给予200mg/kg剂量的BBR,称为LD + BBR组(n = 40)。光照和灌胃完成后,从小鼠收集眼组织。进行苏木精和伊红(HE)染色以观察小檗碱对小鼠慢性视网膜光损伤的保护作用。进行TUNEL检测以评估小檗碱对慢性视网膜光损伤小鼠凋亡细胞的影响。此外,进行定量聚合酶链反应(QPCR)以评估BBR缓解慢性视网膜光损伤中P2X7受体的表达水平。

结果

与空白对照组相比,LD组视网膜形态异常,一些神经节细胞核减少、染色加深且排列疏松。在LD组中,内核层细胞排列似乎稍疏松,而外核层细胞排列紊乱。此外,LD组小鼠视网膜外核层厚度为(47.11±2.01)μm,在外核层观察到大量凋亡细胞,凋亡率为(71.16±5.99)%(P < 0.05)。相比之下,LD + BBR组视网膜形态异常较轻,神经节细胞排列疏松。在LD + BBR组中,视网膜内外核层细胞形态相对完整,染色均匀,排列紧密。此外,外核层厚度测量值为(54.07±2.05)μm,仅存在少数凋亡细胞,凋亡率为(16.02±2.68)%(P < 0.05)。与空白对照组相比,LD组视网膜中P2X7R mRNA的相对表达上调,两组间差异具有统计学意义(P < 0.05)。LD + BBR组视网膜中P2X7R mRNA的相对表达下调,与空白对照组相比无统计学意义。然而,与LD组相比,LD + BBR组视网膜中P2X7R mRNA的相对表达呈显著下降趋势,两组间差异具有统计学意义(P < 0.05)。

结论

小檗碱可减轻小鼠慢性视网膜光损伤,并抑制P2X7R的激活,从而防止视网膜光损伤的形成。

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