雷帕霉素灌胃对糖尿病大鼠视网膜的保护作用及机制  

Protective effect of intragastric administration of rapamycin on retinas of diabetes rats and its mechanism

作　　者：哈利 王琴[2] 杨烨 HA Li;WANG Qin;YANG Ye(Department of Emergency Medicine,Longhua District Central Hospital,Shenzhen 518110,China;不详)

机构地区：[1]深圳市龙华区中心医院急诊内科,广东深圳518110 [2]新疆医科大学第二附属医院老年病科干部病房

出　　处：《山东医药》2023年第2期38-41,46,共5页Shandong Medical Journal

基　　金：新疆维吾尔自治区“青年科技人才—乡村振兴”项目(WJWY-XCZX202209);新疆维吾尔自治区自然科学基金(2020D01C192)。

摘　　要：目的观察雷帕霉素对糖尿病大鼠视网膜的保护作用,并探讨其作用机制与PI3K/AKT/mTOR信号通路的关系。方法将50只大鼠随机分为正常对照组10只和糖尿病组40只,糖尿病组采用高脂饮食及腹腔注射链脲佐菌的方式制作糖尿病模型,对照组给予普通饲料喂养。取造模成功的30只大鼠,随机分为模型对照组、阳性对照组和雷帕霉素组各10只,阳性对照组给予二甲双胍20 mg/(kg·d)灌胃,雷帕霉素组给予雷帕霉素1 mg/(kg·d)灌胃,模型对照组给予等体积纯净水灌胃。4周后大鼠取血检测空腹血糖;取视网膜组织,行HE染色后观察视网膜神经细胞数及视网膜病理组织形态变化;Western blotting法检测视网膜组织中PI3K、AKT、mTOR蛋白表达。结果与正常对照组比较,模型对照组、阳性对照组及雷帕霉素组空腹血糖均升高(P均<0.05);与模型对照组比较,阳性对照组和雷帕霉素组空腹血糖均降低(P均<0.05)。正常对照组视网膜形态无明显病理改变;与正常对照组比较,模型对照组视网膜形态改变,细胞水肿严重,细胞膜结构紊乱,视网膜厚度明显变薄,神经节细胞数量减少;与模型对照组比较,阳性对照组和雷帕霉素组视网膜虽同样出现病理改变程度减轻,神经节细胞计数增多;与阳性对照组相比,雷帕霉素组视网膜病理改变则更轻,神经节细胞计数增多。与正常对照组相比,模型对照组、阳性对照组及雷帕霉素组PI3K、AKT表达水平降低,mTOR表达水平升高;与模型对照组相比,阳性对照组与雷帕霉素组PI3K、AKT表达水平升高,mTOR表达水平降低;与阳性对照组相比,雷帕霉素组AKT表达水平升高,mTOR表达水平降低(P均<0.05)。结论雷帕霉素可有效改善糖尿病所致大鼠视网膜病理损伤,PI3K/AKT/mTOR表达水平可能是其中的机制之一。Objective To observe the protective effect of rapamycin on retinas in diabetes rats,and to explore the relationship between its mechanism and the expression level of PI3K/AKT/mTOR signaling pathway.Methods Fifty rats were randomly divided into the normal control group(10 rats)and diabetes group(40 rats).The rats in the diabetes group were treated with high-fat diet and intraperitoneal injection of streptozotocin to make the diabetic models,and the rats in the control group were fed with normal diet.Thirty rats of successful modeling were randomly divided into the model control group,positive control group,and rapamycin group.The rats in the positive control group were given metformin 20mg/(kg·d)by gavage,the rats in the rapamycin group were given rapamycin 1 mg/(kg·d)by gavage,and the rats in the model control group were given the equal volume of purified water by gavage.After 4 weeks,the rats were anesthetized,and the fasting blood glucose was measured.Retinal tissue was taken and HE staining was performed to observe the number of retinal nerve cells and morphological changes of retinal pathological tissues.Western blotting was used to detect PI3K/AKT/mTOR expression in the retinal tissues.Results Compared with the normal control group,the fasting blood glucose in the model control group,positive control group,and rapamycin group increased(all P<0.05).Compared with the model control group,the fasting blood glucose in the positive control group and rapamycin group decreased(both P<0.05).The retinal morphology of the normal control group did not significantly pathologically change.Compared with the normal control group,the retinal morphology of the model control group changed,with severe cell edema,disorganized cell membrane structure,significantly thinner retinal thickness and reduced number of ganglion cells;compared with the model control group,the retina of the positive control and rapamycin groups also showed reduced pathological alterations and increased ganglion cell count;compared with the positive contr

关 键 词：雷帕霉素 糖尿病视网膜病变 PI3K/AKT/mTOR信号通路 

分 类 号：R587.2[医药卫生—内分泌]