目的：探究原花青素通过AMPK/Wnt/β-catenin通路对形觉剥夺性近视豚鼠视网膜自噬与凋亡的调控作用。

方法：将50只豚鼠随机分为正常对照组、近视模型组、原花青素低、中、高剂量组(25、50、100 mg/kg)，采用带状光检影镜与A超测量右眼屈光度与眼轴长度，HE染色观察视网膜病理变化。免疫组化检测视网膜中p-AMPK、p-mTOR表达，免疫荧光检测视网膜中p62、LC3表达，TUNEL染色检测视网膜细胞凋亡情况，Western blot法检测视网膜中AMPK/Wnt/β-catenin通路、自噬相关蛋白(p62、Beclin1、LC3-II/LC3-I)、凋亡相关蛋白(Bax、Bcl-2、Cleaved-Caspase3、Caspase3)表达情况。

结果：与正常对照组相比，近视模型组屈光度显著降低，眼轴长度显著增加(均P<0.05)； 视网膜细胞排列稀疏且厚度变薄，视网膜中p-AMPK显著降低，p-mTOR显著增加(均P<0.05)，AMPK-Wnt/β-catenin通路被抑制； p62显著增加、LC3显著降低(均P<0.05)，自噬被抑制； Bax与Cleaved-Caspase3显著增加、Bcl-2显著降低，细胞凋亡显著增加(均P<0.05)。与近视模型组相比，原花青素各剂量组均可显著抑制屈光度降低与眼轴长度增加(均P<0.05)，恢复视网膜细胞排列与厚度，激活AMPK/Wnt/β-catenin通路，显著增加p-AMPK表达，抑制p-mTOR表达(均P<0.05)； 显著抑制p62表达，增加Beclin1与LC3-II/LC3-I表达(均P<0.05)，激活视网膜自噬； 显著抑制Bax与Cleaved-Caspase3表达，增加Bcl-2表达(均P<0.05)，抑制视网膜细胞凋亡。

结论：原花青素通过激活AMPK/Wnt/β-catenin通路增强视网膜自噬，抑制视网膜细胞凋亡，预防或缓解近视的发生。

METHODS:Fifty guinea pigs were randomly divided into a normal control group, a myopia model group, and low-dose, medium-dose, and high-dose proanthocyanidins groups(25, 50 and 100 mg/kg). Refractive power and axial length of right eye were measured using a retinoscope and A-scan ultrasound. Retinal pathological changes were observed via HE staining. Immunohistochemistry assessed p-AMPK and p-mTOR expression in the retina. Immunofluorescence detected p62 and LC3 expression. TUNEL staining evaluated retinal cell apoptosis. Western blot examined expression of proteins related to the AMPK/Wnt/β-catenin pathway and autophagy(p62, Beclin1, LC3-II/LC3-I), and apoptosis-related proteins(Bax, Bcl-2, Cleaved-Caspase3, Caspase3)in the retina.

RESULTS:Compared with the control group, the myopia model group showed significantly reduced refractive power and significantly increased axial length(both P<0.05); retinal cell arrangement became sparse and retinal thickness thinned. The p-AMPK levels in the retina were significantly reduced, while p-mTOR levels were significantly increased(both P<0.05), indicating suppression of the AMPK-Wnt/β-catenin pathway. The p62 levels were significantly elevated and LC3 levels were significantly reduced(both P<0.05), suggesting inhibition of autophagy. Bax and Cleaved-Caspase3 were significantly increased, while Bcl-2 was significantly decreased, indicating significantly increased apoptosis(both P<0.05). Compared with the myopia model group, all proanthocyanidins dose groups significantly inhibited refractive error reduction and axial length growth(both P<0.05), restored retinal cell alignment and thickness, activated the AMPK/Wnt/β-catenin pathway, significantly increased p-AMPK expression, and suppressed p-mTOR expression(all P<0.05); significantly suppressed p62 expression, increased Beclin1 and LC3-II/LC3-I expression(both P<0.05), and activated retinal autophagy; significantly suppressed Bax and Cleaved-Caspase3 expression, increased Bcl-2 expression(both P<0.05), and inhibited retinal cell apoptosis.

CONCLUSION:Proanthocyanidins enhance retinal autophagy by activating the AMPK/Wnt/β-catenin pathway, thereby inhibiting retinal apoptosis and preventing or alleviating the onset of myopia.