Du Yongle, Pang Mengran, Chen Haoyu, Zhou Xiangkun, Geng Ruyue, Zhang Yanan, Yang Linqi, Li Jiawen, Han Yufeng, Liu Jinpeng, Zhang Ruixue, Bi Hongsheng, Guo Dadong
Shandong University of Traditional Chinese Medicine, Jinan, China.
Affiliated Eye Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China.
PLoS One. 2024 Dec 3;19(12):e0312379. doi: 10.1371/journal.pone.0312379. eCollection 2024.
This study endeavored to uncover the mechanisms by which Zhujing pill (ZJP) slows myopia progression.
We employed biometric analyses to track diopter and axial length changes in guinea pigs with negative lens-induced myopia (LIM). Through integrating metabonomics and network pharmacology, we aimed to predict the anti-myopic targets and active ingredients of ZJP. Subsequent analysis, including real-time fluorescent quantitative PCR (qPCR) and Western blotting (WB), assessed the expression levels of CHRNA7, LPCAT1, and NOS2 in retinal tissues.
Our findings demonstrate that ZJP significantly mitigates diopter increase and axial elongation in LIM guinea pigs. Metabonomic analysis revealed significant changes in 13 serum metabolites, with ZJP reversing the expression of 5 key metabolites. By integrating metabonomics with network pharmacology, we identified core targets of ZJP against myopia and constructed a compound-gene-disease-metabolite network. The expressions of LPCAT1 and CHRNA7 were found to decrease in the LIM group but increase with ZJP treatment, whereas NOS2 expression showed the opposite pattern.
This investigation provides the first evidence of ZJP's multifaceted effectiveness in managing myopia, highlighting its impact on multiple components, targets, and pathways, including the novel involvement of LPCAT1 and CHRNA7 in myopia pathogenesis.
本研究致力于揭示驻景丸(ZJP)减缓近视进展的机制。
我们采用生物测量分析来跟踪负透镜诱导近视(LIM)豚鼠的屈光度和眼轴长度变化。通过整合代谢组学和网络药理学,我们旨在预测ZJP的抗近视靶点和活性成分。随后的分析,包括实时荧光定量PCR(qPCR)和蛋白质免疫印迹法(WB),评估视网膜组织中CHRNA7、LPCAT1和NOS2的表达水平。
我们的研究结果表明,ZJP显著减轻了LIM豚鼠的屈光度增加和眼轴伸长。代谢组学分析显示13种血清代谢物有显著变化,ZJP逆转了5种关键代谢物的表达。通过将代谢组学与网络药理学相结合,我们确定了ZJP抗近视的核心靶点,并构建了一个化合物-基因-疾病-代谢物网络。发现LIM组中LPCAT1和CHRNA7的表达降低,但经ZJP治疗后增加,而NOS2的表达则呈现相反的模式。
本研究首次提供了ZJP在控制近视方面多方面有效性的证据,突出了其对多个组成部分、靶点和途径的影响,包括LPCAT1和CHRNA7在近视发病机制中的新参与。