RU486通过Notch1/Hes-1信号通路对糖尿病大鼠视网膜神经节细胞的保护作用及机制研究  

Protective effect of RU486 on retinal ganglion cells in diabetic rats via Notch1/Hes-1 signaling pathway

作　　者：刘文强 刘学政 左中夫 LIU Wenqiang;LIU Xuezheng;ZUO Zhongfu(Department of Anatomy,School of Basic Medicine,Jinzhou Medical University,Jinzhou 121000)

机构地区：[1]锦州医科大学基础医学院解剖学教研室,锦州121001

出　　处：《陕西医学杂志》2020年第6期656-658,671,共4页Shaanxi Medical Journal

基　　金：国家自然科学基金资助项目(81571383);中国博士后科学基金资助项目(2017M612870);辽宁省自然科学基金资助项目(201602340)。

摘　　要：目的:探讨RU486对糖尿病大鼠视网膜神经节细胞(RGC)的保护作用及机制。方法:雄性SD大鼠40只,采用随机数字表法分成对照组(CON)、糖尿病组(DM)、RU486治疗组及RU486+DAPT(Notch1信号通路抑制剂)组。后三组大鼠采用单次腹腔注射链脲佐菌素(STZ,50 mg/kg)诱导糖尿病模型。模型诱导成功后,RU486组及RU486+DAPT组大鼠腹腔注射RU486[20 mg/(kg·d)],RU486+DAPT组给予DAPT 5μl(10μmol/L)玻璃体内注射给药。12周后,试剂盒检测大鼠血清糖皮质激素(GC)浓度,免疫荧光染色检测视网膜Notch1表达, Western印迹检测Notch1、Hes-1、GAP-43相对表达量,HE染色检测RGC密度。结果:与CON组相比,DM组及RU486+DAPT组GC浓度、GAP-43表达明显增加,Notch1、Hes-1表达、RGC密度明显降低(均P<0.05);而与DM组相比,RU486组RGC密度、Notch1、Hes-1及GAP-43表达均明显增加(均P<0.05),而DM组与RU486+DAPT组之间比较无统计学差异(P> 0.05)。结论:RU486对糖尿病状态下RGC损伤具有神经保护作用,其机制与激活Notch1/Hes-1信号通路有关。Objective:To explore the protective and mechanism of RU486 on retinal ganglion cells(RGC) in diabetic rats.Methods:Forty male SD rats were randomly divided into control group(CON group),diabetes group(DM group),RU486 treatment group and RU486+DAPT(Notch1 signal pathway inhibitor) group.In the last three groups,the DM model was induced by a single intraperitoneal(IP) injection of streptozotocin(STZ,50 mg/kg).After the model was induced successfully,rats in RU486 treatment group and RU486+DAPT group were intraperitoneally injected with RU486 [20 mg/(kg·d)],while rats in RU486+DAPT group were intravitreally injected with DAPT 5 μl(10 μmol/L).12 weeks later,the concentration of serum glucocorticoid(GC) was detected by kit,the expression of Notch1 in retina was detected by immunofluorescence staining,the relative expression of Notch1,Hes-1 and GAP-43 was detected by Western blot,and the density of RGC was detected by HE staining.Results:Compared with CON group,the concentration of GC and the expression of GAP-43 in DM group and RU486+DAPT group were significantly increased,while the expression of Notch1,Hes-1 and the density of RGC were significantly decreased(all P<0.05).Compared with DM group,the density of RGC,the expression of Notch1,Hes-1 and GAP-43 in RU486 treatment group were significantly increased(all P<0.05),but there was no significant difference between DM group and RU486+DAPT group(P>0.05).Conclusion:RU486 has neuroprotective effect on RGC injury in DM state,and its mechanism is related to the activation of Notch1/Hes-1 signaling pathway.

关 键 词：糖皮质激素 糖尿病视网膜病变 Notch1/Hes-1信号通路 生长相关蛋白-43 RU486 视网膜神经节细胞 大鼠 

分 类 号：R361[医药卫生—病理学]