褪黑素调控STAT3/SOCS3/NF-κB信号通路对大鼠视网膜缺血-再灌注损伤的减轻作用OA
Alleviating effect of melatonin on retinal ischemia-reperfusion injury in rats by regulating the STAT3/SOCS3/NF-κB signaling pathway
目的 探讨褪黑素是否通过调控STAT3/SOCS3/NF-κB信号通路减轻大鼠视网膜缺血-再灌注损伤(RIRI)后的炎症反应与神经损伤.方法 将36只SPF级健康成年雄性SD大鼠随机分为假手术组(Sham组)、RIRI组以及RIRI+褪黑素干预组(RIRI+Mel组),每组12只.采用急性高眼压法建立RIRI模型,RIRI+Mel组大鼠于造模前、后30 min腹腔注射褪黑素(10 mg·kg-1).造模后24 h,进行HE染色观察视网膜组织形态改变;ELISA检测各组大鼠血清IL-1β和IL-10水平;Brn-3a免疫组织化学染色计数各组大鼠视网膜神经节细胞(RGCs);免疫荧光染色与Western blot检测各组大鼠视网膜组织p-STAT3、p-NF-κB及SOCS3蛋白表达.结果 与Sham组相比,RIRI组大鼠视网膜结构紊乱,组织水肿显著,RGCs数量减少,血清IL-1β水平和IL-10水平均升高,大鼠视网膜组织p-STAT3和p-NF-κB表达上调,SOCS3表达下调(均为P＜0.05).与RIRI组相比,褪黑素干预后RIRI+Mel组大鼠视网膜病理损伤减轻,RGCs数量回升,血清IL-1β水平下降、IL-10水平升高,大鼠视网膜组织p-STAT3和p-NF-κB表达降低,SOCS3表达升高(均为P＜0.05).在p-STAT3、SOCS3及p-NF-κB表达方面,Western blot结果与免疫荧光染色结果一致.结论 褪黑素可能通过调控STAT3/SOCS3/NF-κB信号通路,抑制促炎因子释放、促进抗炎因子表达,从而减轻RIRI后的视网膜炎症损伤,发挥神经保护作用.
Objective To investigate whether melatonin alleviates the inflammatory response and neural damage af-ter rat retinal ischemia-reperfusion injury(RIRI)by regulating the STAT3/SOCS3/NF-κB signaling pathway.Methods Thirty-six SPF-grade healthy adult male SD rats were randomly divided into a sham operation group(Sham group),an RIRI group,and an RIRI+melatonin intervention group(RIRI+Mel group),with 12 rats in each group.The RIRI model was es-tablished using the acute high intraocular pressure method.In the RIRI+Mel group,melatonin(10 mg·kg-1)was adminis-tered intraperitoneally to rats 30 minutes before and after model establishment.Twenty-four hours after model establish-ment,morphological changes in retinal tissues were observed using hematoxylin-eosin(HE)staining;serum interleukin(IL)-1β and IL-10 levels of rats in each group were detected by an enzyme-linked immunosorbent assay(ELISA);the num-ber of retinal ganglion cells(RGCs)in each group was counted using Brn-3a immunohistochemical staining;and p-STAT3,p-NF-κB,and SOCS3 protein expression in retinal tissues of rats in each group were detected using immunofluorescence staining and Western blot.Results Compared with the Sham group,rats in the RIRI group showed disordered retinal structure,significant tissue edema,reduced RGC count,elevated serum IL-1β and IL-10 levels,as well as upregulated expres-sion of p-STAT3 and p-NF-κB,and downregulated expression of SOCS3 in retinal tissues(all P＜0.05).Compared with the RIRI group,rats in the RIRI+Mel group showed reduced retinal pathological injury,increased RGC count,decreased serum IL-1β level,elevated IL-10 level,as well as downregulated expression of p-STAT3 and p-NF-κB,and upregulated expression of SOCS3 in retinal tissues after melatonin intervention(all P＜0.05).Western blot results for p-STAT3,SOCS3,and p-NF-κB expression were consistent with immunofluorescence staining results.Conclusion Melatonin may inhibit the release of pro-inflammatory factors and promote the expression of anti-inflammatory factors by regulating the STAT3/SOCS3/NF-κB signaling pathway,thereby alleviating retinal inflammatory injury after RIRI and exerting a neuroprotective effect.
徐晓漫;肖培伦;张丽军;刘中宝;王晓莉;赵岩松
261031 山东省潍坊市,山东第二医科大学附属医院眼科261053 山东省潍坊市,山东第二医科大学基础医学院解剖教研室261031 山东省潍坊市,山东第二医科大学附属医院眼科261031 山东省潍坊市,山东第二医科大学附属医院眼科261053 山东省潍坊市,山东第二医科大学医学影像学院261031 山东省潍坊市,山东第二医科大学附属医院眼科
医药卫生
褪黑素视网膜缺血-再灌注损伤STAT3/SOCS3/NF-κB通路炎症大鼠
melatoninretinal ischemia-reperfusion injurySTAT3/SOCS3/NF-κB pathwayinflammationrats
《眼科新进展》 2026 (5)
354-358,5
山东省自然科学基金资助项目(编号:ZR2021MH351)
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