文章摘要
张博 ,李凤君 ,刘学政 ,左中夫.Maresin1通过抑制JAK2/STAT3信号通路减轻糖尿病大鼠视网膜神经炎症反应[J].神经损伤功能重建,2023,(12):709-713
Maresin1通过抑制JAK2/STAT3信号通路减轻糖尿病大鼠视网膜神经炎症反应
Maresin1 Improves Neuroinflammation of Muller Cells in Diabetic Rats by Inhibiting JAK2/STAT3 Signaling Pathway
  
DOI:
中文关键词: Maresin1  糖尿病视网膜病变  JAK2/STAT3  炎症反应
英文关键词: Maresin1  diabetic retinopathy  JAK2/STAT3  inflammation
基金项目:国家自然科学基金 (No. 81571383); 中国博士后科学基 金项目(No. 2017 M612870)
作者单位
张博1 ,李凤君2 ,刘学政3 ,左中夫3 1. 锦州爱尔眼科医 院有限公司眼科视 光 及 小 儿 眼 病 科 室 2. 唐山市眼科医院 白内障科 3. 锦州医科大学基 础医学院解剖学教 研室 
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中文摘要:
      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 5 μL(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。
英文摘要:
      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. Intraperitoneal 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 5 μL of colivelin (10 - 4 μmol L-1). Samples were collected after 12 weeks. HE staining was used to visualize histopathological changes in retinal tissue. 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-α were 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 decreased IL-6, IL-1β, TNF-α, p-JAK2, and p-STAT3 expression (P<0.01). Compared to the MaR1 group, the Colivelin 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 reversed 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.
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