摘要
[目的]探讨依那西普对糖尿病视网膜病变(DR)大鼠神经元细胞凋亡及Fas、caspase-8表达的影响.[方法]30只SPF级SD大鼠随机分为对照组、模型组、依那西普组,每组10只.依那西普组大鼠DR建模成功后在大腿前侧皮下注射0.4mg/kg依那西普溶液,1次/d,连续8周;对照组及模型组在同时间腹腔注射等量pH4.5的0.01 mol/L柠檬酸-柠檬酸钠缓冲溶液.药物干预结束后,原位末端标记(TUNEL)技术检测各组大鼠视网膜神经元细胞凋亡情况,并计算凋亡指数(AI);检测各组大鼠血清超氧化物歧化酶(SOD)活性及活性氧簇(ROS)、丙二醛(MDA)水平;免疫印迹法检测各组大鼠视网膜组织中Fas、半胱氨酸天冬氨酸蛋白酶-8(caspase-8)蛋白水平.[结果]模型组及依那西普组大鼠神经元细胞出现凋亡现象.与对照组比较,模型组、依那西普组大鼠神经元细胞AI、血清SOD活性及视网膜组织中Fas、caspase-8蛋白水平均升高(P<0.05),血清MDA、ROS水平均降低(P<0.05);依那西普组大鼠神经细胞AI、血清SOD活性、视网膜组织中Fas、caspase-8蛋白水平低于模型组(P<0.05),血清MDA、ROS水平高于模型组(P<0.05).[结论]依那西普可能通过抑制DR大鼠神经元细胞氧化应激反应,抑制Fas/caspase-8通路活化,进而抑制神经元细胞凋亡.
【Objective】To investigate the effect of etanercept on neuronal apoptosis and the expression of Fas and caspase-8 in diabetes retinopathy(DR)rats.【Methods】A total of 30 SPF SD rats were randomly divided into control group,model group and etanercept group with 10 rats in each group.After DR modeling of rats in the etanercept group was successful,0.4 mg/kg etanercept solution was subcutaneously injected into the front thigh once a day for 8 weeks;The control group and the model group were intraperitoneally injected with 0.01 mol/L citric acid sodium citrate buffer solution of the same pH 4.5 at the same time.After drug intervention,apoptosis of retinal neurons in each group was detected by in situ terminal labeling(TUNEL),and apoptosis index(AI)was calculated;The activity of superoxide dismutase(SOD)and the levels of reactive oxygen species(ROS)and malonaldehyde(MDA)in serum were measured;The levels of Fas and caspase-8 protein in the retina of rats in each group were detected by Western blot.【Results】Apoptosis appeared in neurons of the model group and the etanercept group.Compared with the control group,the activity of AI in neuron cells,the activity of SOD in serum,and the levels of Fas and caspase-8 protein in retina of rats in the model group and the etanercept group increased(P<0.05),while the levels of MDA and ROS in serum decreased(P<0.05);The AI of nerve cells,the activity of SOD in serum,the level of Fas and caspase-8 protein in retinal tissue of rats in the etanercept group were lower than those in the model group(P<0.05),and the levels of MDA and ROS in serum were higher than those in the model group(P<0.05).【Conclusion】Etanercept may inhibit the activation of Fas/caspase-8 pathway by inhibiting the oxidative stress response of neurons in DR rats,thereby inhibiting neuronal apoptosis.
作者
王昆
张丽华
甘雪峰
王晓丽
WANG Kun;ZHANG Li-hua;GAN Xue-feng(Department of Pharmacy,Shaanxi Hospital of Traditional Chinese Medicine,Xi'an Shaanxi 710030)
出处
《医学临床研究》
CAS
2023年第1期34-36,40,共4页
Journal of Clinical Research
