Wu Lingling, Gao Lijuan, Cao Yaohui, Chen Fengju, Sun Ting, Liu Yahong
Department of Gynaecology, Second Affiliated Hospital of Xingtai Medical College, Xingtai City 054000, China.
Department of Clinical Medicine, Xingtai Medical College, Xingtai City 054000, China.
Saudi J Biol Sci. 2019 Dec;26(8):2096-2101. doi: 10.1016/j.sjbs.2019.09.032. Epub 2019 Oct 16.
In order to study the protection mechanism of liraglutide on the infectious lesion of the retina of type I diabetes, in this experiment, a mouse model of type I diabetes was established by induction with streptozotocin (STZ) and feeding with high-fat and high-sugar diet. After observing the living conditions of the modeled mice and detecting their fasting blood glucose (FBG), it was found that the modeled mice exhibited clinically similar symptoms in patients with type I diabetes, and their FBG was larger than 16.7 mmol/L, indicating that the experimental mouse model was obtained. The mice were divided into groups. The control group was divided into negative control group (A), light positive control group (B), diabetic control group (C), and diabetes care group (D) according to different treatment methods, and the experimental group was divided into treatment group 1 (LR1), treatment group 2 (LR2) and treatment group 3 (LR3) according to different injection doses. The eyes of mice in each group were extracted and retinal tissue sections were made, and the sections were stained with HE. The retinal morphology was observed and it was found that compared with group A, the outer nucleus layer was significantly thinner in group B and C, and the group D was the thinnest. After treatment with liraglutide, the outer nuclear layer of LR1 group and LR2 group LR3 group recovered significantly, indicating that liraglutide had protective effect on type I diabetes and light-induced damage of mouse retinal photoreceptor cells. Immunohistochemistry was used to detect p-Erk1/2 and ASK1 protein contents in retina. It was found that compared with the negative control group and the light control group, p-Erk1/2 protein contents in LR1, LR2 and LR3 groups were significantly increased, showing statistical significance. Compared with the negative control group and the light control group, ASK1 protein content in LR1, LR2 and LR3 groups significantly decreased. This suggested that the protective mechanism of liraglutide on retinopathy was related to up-regulation of antioxidant protein p-Erk1/2 and down-regulation of apoptosis-related protein ASK1, that is to say, the action site of liraglutide may be related to this. Through real-time quantitative detection of the Trx gene expression level in diabetic and photodamaged mice, it was found that compared with the diabetic light group, the Trx expression level in mice treated with liraglutide showed a significant up-regulated trend, suggesting that the protective mechanism of liraglutide on retinopathy was related to the up-regulated expression of antioxidant protein Trx. Therefore, liraglutide has a certain protective effect on diabetic retinal injury, and its mechanism is related to the up-regulation of p-Erk1/2 and Trx antioxidant protein, and the down-regulation of apoptosis-related protein ASK1.
为研究利拉鲁肽对Ⅰ型糖尿病视网膜感染性病变的保护机制，本实验通过链脲佐菌素（STZ）诱导并高脂高糖饮食喂养建立Ⅰ型糖尿病小鼠模型。观察造模小鼠的生存状况并检测其空腹血糖（FBG），发现造模小鼠呈现出与Ⅰ型糖尿病患者临床上相似的症状，且其FBG大于16.7 mmol/L，表明获得了实验性小鼠模型。将小鼠分组。对照组根据不同治疗方法分为阴性对照组（A）、轻度阳性对照组（B）、糖尿病对照组（C）和糖尿病护理组（D），实验组根据不同注射剂量分为治疗组1（LR1）、治疗组2（LR2）和治疗组3（LR3）。提取各组小鼠的眼睛并制作视网膜组织切片，切片进行HE染色。观察视网膜形态，发现与A组相比，B组和C组的外核层明显变薄，D组最薄。利拉鲁肽治疗后，LR1组、LR2组和LR3组的外核层明显恢复，表明利拉鲁肽对Ⅰ型糖尿病及光诱导的小鼠视网膜光感受器细胞损伤具有保护作用。采用免疫组织化学法检测视网膜中p-Erk1/2和ASK1蛋白含量。发现与阴性对照组和轻度对照组相比，LR1、LR2和LR3组的p-Erk1/2蛋白含量显著增加，具有统计学意义。与阴性对照组和轻度对照组相比，LR1、LR2和LR3组的ASK1蛋白含量显著降低。这表明利拉鲁肽对视网膜病变的保护机制与抗氧化蛋白p-Erk1/2的上调和凋亡相关蛋白ASK1的下调有关，也就是说，利拉鲁肽的作用位点可能与此有关。通过实时定量检测糖尿病和光损伤小鼠中Trx基因表达水平，发现与糖尿病光照组相比，利拉鲁肽治疗小鼠中Trx表达水平呈显著上调趋势，表明利拉鲁肽对视网膜病变的保护机制与抗氧化蛋白Trx的表达上调有关。因此，利拉鲁肽对糖尿病视网膜损伤具有一定的保护作用，其机制与p-Erk1/2和Trx抗氧化蛋白的上调以及凋亡相关蛋白ASK1的下调有关。
