Abstract
Objective To investigate the effect of wogonin(WOG)on retinal ganglion cell(RGC)damage in chron-ic glaucoma rats and its relationship with the regulation of the JAK2/STAT3 signaling pathway.Methods A chronic glau-coma rat model was established in SPF-grade healthy male SD rats(50 modeled successfully).Successfully modeled rats were randomly divided into 6 groups(n=10 per group).The model group received an equal volume of normal saline(once daily,10 mL·kg-1 by gavage and 1 mL·kg-1 by intraperitoneal injection).The low-dose WOG group(L-WOG),medium-dose WOG group(M-WOG),and high-dose WOG group(H-WOG)received WOG at 7 mg·kg-1,14 mg·kg-1,and 28 mg·kg-1 by gavage,respectively(once daily,gavage volume 10 mL·kg-1).The high-dose WOG+Colivelin group(H-WOG+Colivelin)received WOG by gavage(28 mg·kg-1,once daily,10 mL·kg-1)plus intraperitoneal injection of the JAK2/STAT3 pathway activator Colivelin(1 mg·kg-1,once daily,injection volume 1 mL·kg-1).An additional 10 normal rats served as the sham-operated control group(Control group),undergoing surgery to expose the superior episcleral vein without cauterization,and receiving normal saline postoperatively in the same manner as the model group.All treatments lasted for 8 weeks.Intraocular pressure was measured using a tonometer.Retinal morphological changes and RGC apopto-sis were assessed by hematoxylin-eosin(HE)staining and TUNEL staining,respectively.Superoxide dismutase(SOD)ac-tivity and malondialdehyde(MDA)content in retinal tissue were measured by ELISA.Protein expression changes in the JAK2/STAT3 signaling pathway in retinal tissue were detected by Western blot.Results Retinal structure was normal in the Control group,with clear layers and densely arranged cells.Compared to the Control group,the model group showed significantly thinner retinal tissue,disorganized structure,sparsely arranged cells,and vacuolation.Compared to the model group,the L-WOG,M-WOG,and H-WOG groups exhibited increased retinal thickness and more orderly cell arrangement.Compared to the H-WOG group,the H-WOG+Colivelin group showed relatively thinner retinal tissue and sparser cell ar-rangement.After intervention,the RGC apoptosis rate in the model group(7.32％±1.07％)was significantly higher than that in the Control group(0.61％±0.12％)(P＜0.05).The apoptosis rates in the L-WOG group(5.67％±0.63％),M-WOG group(3.34％±0.75％),and H-WOG group(1.12％±0.35％)were significantly lower than that in the model group(all P＜0.05),showing a dose-dependent decreasing trend.The apoptosis rate in the H-WOG+Colivelin group(6.83％±1.56％)was significantly higher than that in the H-WOG group(P＜0.05).Compared to the Control group,SOD activity in the retinal tissue of the model group was significantly decreased(P＜0.05),while MDA content was significantly increased(P＜0.05).Compared to the model group,SOD activity was significantly increased and MDA content was significantly de-creased in the L-WOG,M-WOG,and H-WOG groups(all P＜0.05),with this effect being dose-dependent(i.e.,H-WOG group＞M-WOG group＞L-WOG group).Compared to the H-WOG group,the H-WOG+Colivelin group showed signifi-cantly decreased SOD activity and significantly increased MDA content(P＜0.05).Compared to the Control group,the ra-tios of p-JAK2/JAK2 and p-STAT3/STAT3 expression in the retinal tissue of the model group were significantly upregulated(all P＜0.05).Compared to the model group,the ratios of p-JAK2/JAK2 and p-STAT3/STAT3 expression were significantly downregulated in the L-WOG,M-WOG,and H-WOG groups(all P＜0.05).Compared to the H-WOG group,the ratios of p-JAK2/JAK2 and p-STAT3/STAT3 expression were significantly upregulated in the H-WOG+Colivelin group(all P＜0.05).Conclusion WOG may alleviate retinal tissue damage in chronic glaucoma rats by inhibiting the JAK2/STAT3 signaling pathway,thereby reducing oxidative stress and RGC apoptosis.关键词
汉黄芩素/JAK2/STAT3信号通路/慢性青光眼/视网膜神经节细胞Key words
wogonin/JAK2/STAT3 signaling pathway/chronic glaucoma/retinal ganglion cells分类
临床医学
