活血通络方调控PI3K/Akt信号通路改善大鼠糖尿病视网膜病变的作用机制研究  

Study on Action Mechanism of Huoxue Tongluo Prescription Regulating PI3K/Akt Signaling Pathway to Improve Diabetic Retinopathy in Rats

作　　者：李能[1] 来坚[1] 舒琼燕 张蕊[1] 朱琳 LI Neng;LAI Jian;SHU Qiongyan;ZHANG Rui;ZHU Lin

机构地区：[1]杭州市中医院眼科,浙江杭州310007

出　　处：《新中医》2022年第24期1-6,共6页New Chinese Medicine

基　　金：浙江省基础公益项目(LGF21H120001)。

摘　　要：目的:探讨活血通络方调控磷酸肌醇3激酶/蛋白激酶B (PI3K/Akt)信号通路改善大鼠糖尿病视网膜病变的作用机制。方法:选取清洁级健康雄性SD大鼠72只,采用随机数字表法分为对照组、模型组及药物组,每组24只。建模成功后,药物组大鼠给予活血通络方10 mL/(kg·d)灌胃,对照组与模型组大鼠给予等剂量0.9%氯化钠注射液灌胃。3组均连续灌胃3个月。比较3组血糖、血脂、氧化应激指标、炎症因子水平及伊文思蓝渗透量;比较3组大鼠视网膜组织紧密连接蛋白-1 (ZO-1)、闭合蛋白(Occludin)、血管内皮钙黏蛋白(VE-Cadherin)、磷酸化磷酸肌醇3激酶(p-PI3K)、磷酸化蛋白激酶B (p-Akt)表达水平;观察大鼠视网膜组织病理学改变。结果:与对照组比较,模型组空腹血糖(FBG)、糖化血红蛋白(HbA1c)、总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白(LDL)、活性氧簇(ROS)、丙二醛(MDA)、谷胱甘肽过氧化物酶(GSH-Px)、白细胞介素-6 (IL-6)、白细胞介素-1β (IL-1β)、肿瘤坏死因子-α (TNF-α)水平均升高(P<0.05),高密度脂蛋白(HDL)、超氧化物歧化酶(SOD)水平均降低(P<0.05),伊文思蓝渗透量增加(P<0.05);与模型组比较,药物组FBG、HbA1c、TC、TG、LDL、ROS、MDA、IL-6、IL-1β、TNF-α水平均降低(P<0.05),HDL、SOD、GSH-Px水平均升高(P<0.05),伊文思蓝渗透量减少(P<0.05)。与对照组比较,模型组大鼠视网膜组织ZO-1、Occludin、VE-Cadherin表达水平均降低(P<0.05),p-PI3K、p-Akt表达水平均升高(P<0.05);与模型组比较,药物组大鼠视网膜组织ZO-1、Occludin、VE-Cadherin表达水平均升高(P<0.05),p-PI3K、p-Akt表达水平均降低(P<0.05)。模型组大鼠视网膜组织细胞排列紊乱、疏松,色素上皮细胞增生,毛细血管明显扩张充血,外层出现新生血管;药物组大鼠视网膜组织较模型组细胞排列整齐、密度增加,视网膜病理学改变明显减轻。结论:活血通络方可能通过抑制PI3K/Akt信号通Objective:To investigate the action mechanism of Huoxue Tongluo Prescription regulating phosphoinositide 3-kinase/protein kinase B(PI3K/Akt) signaling pathway to improve diabetic retinopathy in rats. Methods:A total of 72 clean grade healthy male SD rats were selected and divided into the control group,the model group and the medication group according to the random number table method,with24 rats in each group. After successful modeling,the medication group was given 10 mL/(kg·d) of Huoxue Tongluo Prescription by gastric irrigation,and the control group and the model group were given the same dose of 0.9% sodium chloride injection by gastric irrigation. All the three groups were given continuous gastric irrigation for three months. The levels of blood glucose,blood lipid,oxidative stress indexes and inflammatory factors as well as the permeation quantity of Evans Blue in the three groups were compared;the expression levels of zonula occludens protein-1(ZO-1),occludin,vascular endothelium-cadherin(VEcadherin),phosphorylated phosphoinositide 3-kinase(p-PI3K) and phosphorylated protein kinase B(p-Akt)in retinal tissues of rats in the three groups were compared;the histopathological changes of retinal tissues in rats were observed. Results: When compared with those in the control group, the levels of fasting blood glucose(FBG),glycosylated hemoglobin(HbA1c),total cholesterol(TC),triglyceride(TG),low density lipoprotein(LDL), reactive oxygen species(ROS), malondialdehyde(MDA), glutathione peroxidase(GSHPx),interleukin-6(IL-6),interleukin-1β(IL-1β) and tumor necrosis factor-α(TNF-α) in the model group were raised(P<0.05),levels of high density lipoprotein(HDL) and superoxide dismutase(SOD) in the model group were reduced(P<0.05),and the permeation quantity of Evans Blue in the model group was increased(P<0.05). When compared with those in the model group,the levels of FBG,HbA1c,TC,TG,LDL,ROS,MDA,IL-6,IL-1β and TNF-α in the medication group were reduced(P<0.05),levels of HDL,SOD and GSH-Px in the medication grou

关 键 词：糖尿病视网膜病变 SD大鼠 活血通络方 血糖 血脂 氧化应激 炎症因子 磷酸肌醇3激酶/蛋白激酶B信号通路 

分 类 号：R285.5[医药卫生—中药学]