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作 者:陆春晖[1] 张敬敬 陶慧文 罗梅[1] 罗荔[1] Lu Chunhui;Zhang Jingjing;Tao Huiwen;Luo Mei;Luo Li(The Fifth Affiliated Hospital of Xinjiang Medical University,Urumqi 830000)
机构地区:[1]新疆医科大学第五附属医院,乌鲁木齐830000
出 处:《国际老年医学杂志》2024年第4期419-426,共8页International Journal of Geriatrics
基 金:新疆维吾尔自治区自然科学基金(2022D01C317)。
摘 要:目的 探讨神经生长因子β(NGFβ)在糖尿病周围神经病变(DPN)中的作用机制。方法 建立高糖细胞模型,并分为对照组、OE-NGFβ组、NC-NGFβ组;建立大鼠糖尿病神经病变模型,并分为大鼠对照组、大鼠OE-NGFβ组、大鼠NC-NGFβ组。利用RT-qPCR和Western blot检测细胞和大鼠坐骨神经中胰岛素样生长因子-1(IGF-1),细胞间黏附分子-1(ICAM-1)、肿瘤坏死因子-α(TNF-α)、自噬相关基因12(ATG12)、微管相关蛋白1A/1B轻链3B(LC3B)和P62的表达变化。利用ELISA检测DPN大鼠血液样本中丙二醛(MDA),一氧化氮(NO),活性氧(ROS)和超氧化物歧化酶(SOD)的水平。结果 与对照组比较OE-NGFβ组中IGF-1、ATG12、LC3B和P62的mRNA和蛋白水平显著升高(P<0.001),ICAM-1、TNF-α的mRNA和蛋白水平则显著下降(P<0.001)。与对照组比较大鼠OE-NGFβ组的坐骨神经中IGF-1、ATG12、LC3B和P62的mRNA和蛋白水平显著升高(P<0.001),ICAM-1、TNF-α的mRNA和蛋白水平显著降低(P<0.001)。此外,与对照组比较大鼠OE-NGFβ组中MDA、NO和ROS的水平显著降低(P<0.001),SOD的水平显著升高(P<0.001)。结论 NGFβ可能通过调节自噬和抗氧化在DPN中发挥神经保护作用,提示NGFβ可能是一个DPN的潜在治疗靶点。Objective To investigate the mechanism of nerve growth factorβ(NGFβ)in diabetic peripheral neuropathy(DPN).Methods High glucose cell model was established and divided into control group,OE-NGFβgroup and NC-NGFβgroup.Diabetic neuropathy model was established and divided into rat control group,OE-NGFβgroup and NC-NGFβgroup.RT-qPCR and Western blot were used to detect the expression changes of insulin-like growth factor-1(IGF-1),intercellular adhesion molecule-1(ICAM-1),tumor necrosis factor-α(TNF-α),autophagy-related gene 12(ATG12),microtubule-associated protein 1A/1B light chain 3B(LC3B)and P62 in cells and rat sciatic nerves.The levels of malondialdehyde(MDA),nitric oxide(NO),reactive oxygen species(ROS)and superoxide dismutase(SOD)in blood samples of DPN rats were detected by ELISA.Results Compared with control group,the mRNA and protein levels of IGF-1,ATG12,LC3B and P62 in the OE-NGFβgroup were significantly increased(P<0.001),while the mRNA and protein levels of ICAM-1 and TNF-αwere significantly decreased(P<0.001).Compared with control group,the mRNA and protein levels of IGF-1,ATG12,LC3B and P62 in the sciatic nerve of the rat OE-NGFβgroup were significantly increased(P<0.001),and the mRNA and protein levels of ICAM-1 and TNF-αwere significantly decreased(P<0.001).In addition,compared with control group,the levels of MDA,NO,and ROS were significantly decreased(P<0.001)and the levels of SOD were significantly increased(P<0.001)in the rat OE-NGFβgroup.Conclusion NGFβmay exert neuroprotective effects in DPN by regulating autophagy and antioxidant,suggesting that NGFβmay be a potential therapeutic target for DPN.
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