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.
Abstract
Objective To investigate the mechanism of nerve growth factor β(NGF β)in diabetic peripheral neuropathy(DPN).Methods High glucose cell model was established and divided into control group,OE-NGFβ group and NC-NGFβ group.Diabetic neuropathy model was established and divided into rat control group,OE-NGFβ group and NC-NGFβ group.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-NGFβ group were significantly increased(P<0.001),while the mRNA and protein levels of ICAM-1 and TNF-α were 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-NGFβ group were sig-nificantly increased(P<0.001),and the mRNA and protein levels of ICAM-1 and TNF-α were 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-NGFβ group.Conclusion NGFβ may exert neuroprotective effects in DPN by regulating autophagy and antioxidant,suggesting that NGFβ may be a potential therapeutic target for DPN.
基金项目
新疆维吾尔自治区自然科学基金(2022D01C317)
国家科技期刊平台
NSTL
万方数据