河北医学2025，Vol.31Issue(7)：1075-1082,8.DOI:10.3969/j.issn.1006-6233.2025.07.04
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
miR-34 Regulating the PI3K/Akt Signaling Pathway and Mediating Autophagy of Lens Epithelial Cells to Improve Cataract
摘要
Abstract
Objective:To explore the regulatory effect of microRNA-34(miR-34)on phosphatidyli-nositol 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 estab-lished by subcutaneous injection of D-galactose.The rats were randomly divided into control group(subcuta-neous 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 injec-tion 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 immunofluo-rescence.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 path-way.Results:Compared with the control group,the expression level of miR-34 in the model group was sig-nificantly decreased(P<0.05),typic al cataract appeared,and the lens turbidity score was significantly in-creased(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 signif-icant 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 re-duced.The fluorescence intensity of ROS,MDA,Beclin-1,LC3 and LC3-Ⅱ/LC3-Ⅰ levels were significant-ly decreased(P<0.05),while the levels of SOD,p62,p-PI3K,p-Akt and p-MTOR were significantly in-creased(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 sig-nificantly decreased(P<0.05),while SOD,p62,p-PI3K,p-Akt and p-MTOR levels were significantly in-creased(P<0.05).Conclusion:miR-34 is expressed at a low level in cataract rats.Upregulating its expres-sion can alleviate oxidative stress and autophagy in rat lens epithelial cells(LECs),and the mechanism in-volved may be related to the activation of the PI3K/Akt signaling pathway.关键词
微小核糖核酸-34/PI3K/Akt信号通路/晶状体上皮细胞/白内障大鼠/自噬Key words
MiR-34/PI3K/Akt signaling pathway/Cataract rat/Lens epithelial cells/Au-tophagy引用本文复制引用
李立宪,李娜,胡俊贵,孙玉亮..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[J].河北医学,2025,31(7):1075-1082,8.基金项目
江苏省优势学科建设工程项目,(编号:YSHL2201-1001) （编号:YSHL2201-1001）
