miR-34调控PI3K/Akt信号通路介导的晶状体上皮细胞自噬改善白内障

doi:10.3969/j.issn.1006-6233.2025.07.04

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Abstract Objective: To explore the regulatory effect of microRNA-34 (miR-34) on phosphatidylinositol 3 kinase (PI3K)/protein kinase B(Akt) signaling pathway and its mechanism in mediating autophagy of lens epithelial cells (LECs) and improving cataract in rats. Methods: The cataract rat model was established by subcutaneous injection of D-galactose. The rats were randomly divided into control group (subcutaneous injection of the same amount of normal saline), model group (subcutaneous injection of 200 mg/kg of D-galactose), NC-agomir group (subcutaneous injection of 200 mg/kg of D-galactose + tail vein injection of NC-agomir) and miR-34 agomir group (subcutaneous injection of 200 mg/kg D-galactose + tail vein injection of 5 nmoL miR-34 agomir) and LY294002 groups (PI3K/Akt pathway inhibitor, 0.3 mg/kg LY294002+ tail vein injection of 5 nmoL miR-34 agomir). Each group consisted of 15 rats. After treatment, RT-qPCR was used to detect the expression level of miR-34 in the lens of each group. The opacity of lens of cataract rats was observed and scored under a microscope. The pathological changes of the rat lens were observed by hematoxylin-eosin (HE) staining. The LC3 autophagosome formation in LECs was detected by immunofluorescence. The oxidative stress levels in LECs were detected by corresponding kits. Western Blot analysis was performed to detect the expression levels of autophagy related proteins in LECs and PI3K/AKT signaling pathway. Results: Compared with the control group, the expression level of miR-34 in the model group was significantly decreased (P<0.05), typic al cataract appeared, and the lens turbidity score was significantly increased (P<0.05), LECs arrangement was disordered, swelling was obvious, tissue structure was severely damaged, and a large number of vacuolates appeared in the cortex. Beclin-1, LC3 fluorescence intensity and LC3-Ⅱ/LC3-I levels were significantly increased, while SOD, p62, p-PI3K, p-Akt and p-MTOR levels were significantly decreased (P<0.05). Compared with the model group, the NC-agomir group had no significant difference in cataract degree, lens turbidity score, and lens pathological injury degree. There were no significant differences in fluorescence intensity of ROS, MDA, Beclin-1, LC3, LC3-Ⅱ/LC3-I, SOD, p62, p-PI3K, p-Akt and p-MTOR (P>0.05). Compared with the NC-agomir group, the miR-34 expression level of rats in the agomir group was significantly increased (P<0.05), lens turbidity score was significantly decreased (P<0.05), epithelial cell morphology was significantly improved, and cortical vacuoles were reduced. The fluorescence intensity of ROS, MDA, Beclin-1, LC3 and LC3-Ⅱ/LC3-I levels were significantly decreased (P<0.05), while the levels of SOD, p62, p-PI3K, p-Akt and p-MTOR were significantly increased (P<0.05). Compared with the miR-34 agomir group, the expression level of miR-34 in LY294002 group had no significant difference (P > 0.05), the lens turbidity score was significantly increased (P<0.05), the uniformity and integrity of epithelial cells were decreased, the cells were mildly swollen and there were a few vacuoles. ROS, MDA, Beclin-1, LC3 fluorescence intensity and LC3-Ⅱ/LC3-I levels were significantly decreased (P<0.05), while SOD, p62, p-PI3K, p-Akt and p-MTOR levels were significantly increased (P<0.05). Conclusion: miR-34 is expressed at a low level in cataract rats. Upregulating its expression can alleviate oxidative stress and autophagy in rat lens epithelial cells (LECs), and the mechanism involved may be related to the activation of the PI3K/Akt signaling pathway.

Key words： MiR-34 PI3K/Akt signaling pathway Cataract rat Lens epithelial cells Autophagy

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	LI Lixian
	LI Na
	HU Jungui
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LI Lixian,LI Na,HU Jungui, et al. miR-34 Regulating the PI3K/Akt Signaling Pathway and Mediating Autophagy of Lens Epithelial Cells to Improve Cataract[J]. HeBei Med, 2025, 31(7): 1075-1082.

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http://www.hbyxzzs.cn/EN/10.3969/j.issn.1006-6233.2025.07.04 OR http://www.hbyxzzs.cn/EN/Y2025/V31/I7/1075

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