摘要
目的:探讨Maresin1(MaR1)对糖尿病(DM)大鼠视网膜神经炎症的影响及其机制。方法:SD大鼠40只,随机分为4组:对照组(Con组)、糖尿病组(DM组)、Maresin1预处理组(MaR1组)和Maresin1+colivelin组(colivelin组)。腹腔注射链脲佐菌素(STZ)构建DM大鼠模型。DM造模成功后,MaR1组大鼠给与MaR1(4 ng/g)腹腔注射,2次/周;Con组和DM组给予等量PBS腹腔注射;Colivelin组在MaR1组给药的基础上,将大鼠麻醉后用微量进样器向玻璃体内一次性注射colivelin 5μL(10^(-4)μmoL/L)。12周后取材。HE染色观察视网膜组织病理改变;免疫组化检测视网膜胶质纤维酸性蛋白(GFAP)表达;ELISA测定视网膜IL-6、IL-1β、TNF-α水平;Western blot检测视网膜IL-6、IL-1β、TNF-α、JAK2/STAT3通路表达水平。结果:与Con组相比,DM组大鼠视网膜的神经节细胞数量明显减少,GFAP表达增多,IL-6、IL-1β、TNF-α、p-JAK2、p-STAT3表达增多(P<0.01)。与DM组相比,MaR1组大鼠视网膜RGC数量增多,GFAP表达减少,IL-6、IL-1β、TNF-α、p-JAK2、p-STAT3表达降低(P<0.01)。与MaR1组相比,colivelin组大鼠视网膜的神经节细胞数量明显减少,GFAP表达增多,IL-6、IL-1β、TNF-α、p-JAK2、p-STAT3表达增多(P<0.01)。结论:MaR1对糖尿病大鼠视网膜炎症具有一定的抑制作用,这可能与抑制JAK2/STAT3通路有关。
Objective:To investigate the effect of Maresin1(MaR1)on retinal neuroinflammation in diabetic(DM)rats and its mechanism.Mtehods:Forty SD rats were randomly divided into 4 groups:the control(Con)group,diabetes(DM)group,Maresin1(MaR1)group,and Maresin1+colivelin(Colivelin)group.Intraperitone-al injections of streptozocin(STZ)were given to establish the rat DM model.After model creation,the MaR1 group was given intraperitoneal injections of MaR1(4 ng/g)2 times per week,and the Con and DM groups were given equal volume injections of PBS.The Colivelin group rats,in addition to receiving the same injections as MaR1 group rats,were anesthetized then given an intravitreal injection of 5μL of colivelin(10^(-4)μmol L-1).Samples were collected after 12 weeks.HE staining was used to visualize histopathological changes in retinal tis-sue.Immunohistochemistry was used to evaluate the expression of glial fibrillary acidic protein(GFAP)in the retina.The levels of retinal IL-6,IL-1β,and TNF-αwere assessed by ELISA.The expression level of retinal IL-6,IL-1β,TNF-α,and JAK2/STAT3 signaling proteins were found by Western blot.Results:Compared to the Con group,the DM group showed a significantly decreased retinal ganglion cell(RGC)number,increased GFAP expression,and increased IL-6,IL-1β,TNF-α,p-JAK2,and p-STAT3 expression(P<0.01).Compared to the DM group,the MaR1 group showed an increased number of RGC,decreased GFAP expression,and de-creased IL-6,IL-1β,TNF-α,p-JAK2,and p-STAT3 expression(P<0.01).Compared to the MaR1 group,the Co-livelin group showed a decreased RGC number,increased GFP expression,and increased IL-6,IL-1β,TNF-α,p-JAK2,and p-STAT3 expression(P<0.01).The protective effect of MaR1 on the retina of DM rats was re-versed when colivelin,a JAK2/STAT3 pathway activator,was administered.Conclusion:MaR1 has a certain inhibitory effect on retinal inflammation in diabetes rats,which may be related to the inhibition of JAK2/STAT3 pathway.
作者
张博
李凤君
刘学政
左中夫
ZHANG Bo;LI Fengjun;LIU Xuezheng;ZUO Zhongfu(Department of Optometry and pediatric Ophthalmology,Jinzhou Aier Eye Hospital Co.,LTD.Ophthalmology,Liaoning Jinzhou 121000,China;Department of Cataract,Tangshan Eye Hospital,Heibei Tangshan,063000,China;Department of Anatomy,School of Basic Medical Sciences,Jinzhou Medical University,Liaoning Jinzhou 121000,China)
出处
《神经损伤与功能重建》
2023年第12期709-713,共5页
Neural Injury and Functional Reconstruction
基金
国家自然科学基金(No.81571383)
中国博士后科学基金项目(No.2017M612870)。
