瑞芬太尼调节JAK2/STAT3信号通路对小鼠视网膜缺血再灌注损伤的影响  

Effect of remifentanil on retinal ischemia-reperfusion injury in mice by regulating the JAK2/STAT3 signaling pathway

作　　者：张晓敏 李晓燕 高晓茹 ZHANG Xiao-min;LI Xiao-yan;GAO Xiao-ru(Department of Chiropractic,Zhangjiakou Fourth Hospital,Zhangjiakou,Hebei Province 075000,China)

机构地区：[1]张家口市第四医院手术麻醉科,河北张家口075000

出　　处：《解剖学研究》2024年第5期462-468,共7页Anatomy Research

基　　金：张家口市重点研发计划项目(2221147D)。

摘　　要：目的探讨瑞芬太尼(RFTN)调节JAK2/STAT3信号通路对小鼠视网膜缺血再灌注(RIRI)损伤的影响。方法将小鼠分为Sham组、Model组、RFTN低剂量组(RFTN-L)、RFTN高剂量组(RFTN-H)和RFTN-H+Colivelin组(JAK2激活剂)组。HE染色观察各组小鼠视网膜形态;TUNEL染色法检测视网膜组织细胞凋亡;ELISA法检测小鼠视网膜组织TNF-α、IL-10和IL-1β水平;商品化试剂盒检测小鼠视网膜组织SOD、MDA、CAT水平;Western blot检测视网膜组织中NLRP3、caspase-1、JAK2、STAT3、cleaved caspase-3蛋白表达水平。结果与Sham组相比,Model组小鼠视网膜组织有明显损伤,GCL厚度和RGC数量、视网膜组织细胞凋亡率、TNF-α和IL-1β水平、MDA含量、NLRP3、caspase-1、cleaved caspase-3、p-JAK2/JAK2、p-STAT3/STAT3蛋白表达水平显著升高,视网膜组织IL-10水平、SOD和CAT活性显著降低(P<0.05);与Model组相比,RFTN-L组和RFTN-H组小鼠视网膜组织损伤明显减轻,GCL厚度和RGC数量、视网膜组织细胞凋亡率、TNF-α和IL-1β水平、MDA含量、NLRP3、caspase-1、cleaved caspase-3、p-JAK2/JAK2、p-STAT3/STAT3蛋白表达水平显著降低,视网膜组织IL-10水平、SOD和CAT活性显著升高(P<0.05);Colivelin可减弱RFTN对RIRI小鼠的保护作用(P<0.05)。结论RFTN可降低RIRI小鼠炎症、氧化应激和视网膜组织细胞凋亡,减轻视网膜损伤,可能与抑制JAK2/STAT3信号通路有关。Objective To investigate the effect of remifentanil(RFTN)on retinal ischemia-reperfusion(RIRI)injury in mice by regulating the JAK2/STAT3 signaling pathway.Methods The mice were separated into Sham group,Model group,RFTN-L low-dose group,RFTN-H high-dose group,and RFTN-H+Colivelin group(JAK2 activator).HE staining was applied to observe the retinal morphology of mice in each group.TUNEL staining method was applied to detect apoptosis in retinal tissue cells.ELISA method was applied to detect the levels of TNF-α,IL-10,and IL-1β in mouse retinal tissue.The commercialized reagent kits were applied to detect the levels of SOD,MDA,and CAT in mouse retinal tissue.Western blot was applied to detect the expression levels of NLRP3,caspase-1,JAK2,STAT3,and cleaved caspase-3 proteins in retinal tissue.Results Compared with the Sham group,the retinal tissue of mice in the Model group showed obvious damage,the thickness of CCL,the number of RGCs,apoptosis rate of retinal tissue cells,levels of TNF-αand IL-1β,content of MDA,the expression levels of NLRP3,caspase-1,cleaved caspase-3,p-JAK2/JAK2,p-STAT3/STAT3 proteins were obviously increased,the level of IL-10,activities of SOD,and CAT in retinal tissue were obviously reduced(P<0.05).Compared with the Model group,the retinal tissue damage of mice in the RFTN-L and RFTN-H groups was obviously reduced,the thickness of GCL,the number of RGCs,apoptosis rate of retinal tissue cells,levels of TNF-α and IL-1β,content of MDA,the expression levels of NLRP3,caspase-1,cleaved caspase-3,p-JAK2/JAK2,p-STAT3/STAT3 proteins were obviously reduced,the level of IL-10,activities of SOD,and CAT in retinal tissue were obviously increased(P<0.05).Colivelin could weaken the protective effect of RFTN on RIRI mice(P<0.05).Conclusion RFTN can reduce inflammation,oxidative stress,and retinal tissue cell apoptosis in RIRI mice,alleviate retinal damage,and may be related to the inhibition of the JAK2/STAT3 signaling pathway.

关 键 词：瑞芬太尼 视网膜 缺血再灌注损伤 JAK2/STAT3信号通路 裂解半胱氨酸天冬氨酸蛋白酶-3 

分 类 号：R774.1[医药卫生—眼科]