夹竹桃麻素调节HMGB1/TLR4/NF-κB信号通路对糖尿病白内障大鼠的改善作用及机制研究  

The ameliorating effect and mechanism of apocynin on diabetic cataract rats by regulating HMGB1/TLR4/NF-κB signaling pathway

作　　者：李鹤一 刘厉严 王佳 Li Heyi;Liu Liyan;Wang Jia(Department of Ophthalmology,Jinqiu Hospital,Liaoning Province,Shenyang 110000,China)

机构地区：[1]辽宁省金秋医院眼科,沈阳110000

出　　处：《临床眼科杂志》2023年第5期459-463,共5页Journal of Clinical Ophthalmology

摘　　要：目的探讨夹竹桃麻素(APO)对糖尿病白内障大鼠的改善作用并分析其可能机制。方法实验研究。SPF级SD大鼠60只,随机分为对照组、模型组、APO低剂量组(10 mg/kg)、APO中剂量组(20 mg/kg)、APO高剂量组(40 mg/kg)和阳性组(100 mg/kg二甲双胍)。用一次性注射链脲菌素(STZ)法构建糖尿病白内障大鼠模型,建模成功后按组别给予不同药物处理。检测大鼠血糖值并测评晶状体混浊程度;HE染色观察晶状体病理学变化;酶联免疫吸附测定(ELISA)检测白细胞介素-6(IL-6)、白细胞介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)水平;试剂盒检测丙二醛(MDA)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)指标;Western Blot检测高迁移率族蛋白1(HMGB1)、Toll样受体4(TLR4)和核转录因子-κB(NF-κB)蛋白表达水平。结果模型组大鼠晶状体混浊,细胞肿胀、破裂、出现空泡,血糖值、MDA、IL-6、IL-1β、TNF-α、HGMB1、TLR4、NF-κB蛋白表达水平升高,SOD和GSH-Px水平降低;与模型组相比,APO各组及阳性组大鼠晶状体混浊程度降低,晶状体病理症状改善,血糖值、MDA、IL-6、IL-1β、TNF-α、HGMB1、TLR4、NF-κB蛋白表达水平有所下降,而SOD和GSH-Px水平则上升。结论APO可能通过抑制HMGB1/TLR4/NF-κB信号通路的激活,改善糖尿病白内障大鼠氧化应激损伤和炎症水平。Objective To investigate the ameliorating effect of apocynin(APO)on diabetic cataract rats and analyze its possible mechanism.Methods A prospective case-control study.Sixty SPF SD rats were randomly divided into control group,model group,APO low-dose group(10 mg/kg),APO medium-dose group(20 mg/kg),and APO high-dose group(40 mg/kg)and positive group(100 mg/kg metformin).A rat model of diabetic cataract was constructed by a one-time injection of streptozotocin(STZ)method,and after successful modeling,different drug treatments were given according to groups.The blood glucose levels in rats were measured and the degree of lens opacity was evaluated.Hematoxylin eosin(HE)staining was applied to observe the pathological changes of the lens.The levels of interleukin-6(IL-6),interleukin-1β(IL-1β)and tumor necrosis factor-α(TNF-α)were detected by enzyme-linked immunosorbent assay(ELISA).The kits were applied to detect malondialdehyde(MDA),superoxide dismutase(SOD),and glutathione peroxidase(GSH-Px)indicators.Western Blot was applied to detect the protein expression levels of high mobility group box 1(HMGB1),Toll-like receptor 4(TLR4)and nuclear transcription factor-κB(NF-κB).Results The lens of the rats in the model group was cloudy,the cells were swollen,ruptured,and with vacuoles,the blood glucose levels,MDA,IL-6,IL-1β,TNF-α,HGMB1,TLR4,NF-κB protein expression levels increased,while SOD and GSH-Px levels reduced.Compared with the model group,the degree of lens opacity of the rats in APO groups and the positive group decreased,the pathological symptoms of the lens ameliorated,the blood glucose levels,MDA,IL-6,IL-1β,TNF-α,HGMB1,TLR4,NF-κB protein expression levels decreased,while SOD and GSH-Px levels increased.Conclusions APO may ameliorate oxidative stress injury and inflammation in diabetic cataract rats by inhibiting the activation of HMGB1/TLR4/NF-κB signaling pathway.

关 键 词：夹竹桃麻素 糖尿病 白内障 氧化应激 炎症 HMGB1/TLR4/NF-κB通路 

分 类 号：R285.5[医药卫生—中药学]