t-PA负向调控p75NRT改变血管外膜自主神经重构参与动脉粥样硬化
发布时间：2019-07-10 14:39
【摘要】：目的研究组织型纤溶酶原激活物(t-PA)对p75NTR、炎性反应、免疫调节、氧化应激的作用,以及对内膜增生的影响。方法对糖尿病兔给予颈动脉外膜剥除建立动物模型,然后进行血管损伤处理,同时给予t-PA控释微球后,免疫荧光染色分别观察对照组和处理组神经重构的变化情况,同时检测给予t-PA控释微球对乙酰胆碱和去甲肾上腺素释放的影响。RT-PCR检测t-PA释控微球对局部血管组织的炎症、免疫反应和氧化应激的影响。采用交感神经元与平滑肌细胞共培养,之后给予乙二醛进行处理作为动脉粥样硬化细胞模型,以t-PA处理组作为干预组,观察t-PA对胆碱能神经元数目,与平滑肌细胞之间的突触连接数目、乙酰胆碱分泌的影响。RT-PCR检测t-PA-MMP-p75NTR-NF-κB信号通路的改变。结果给予t-PA控释微球能明显增加胆碱能神经元数目和神经纤维(P0.05)而不影响去甲肾上腺素能神经元数目和神经纤维(P0.05),并且导致乙酰胆碱释放增多(P0.05),最终抑制内膜增生(P0.05)。离体交感神经元与平滑肌细胞共培养,之后给予乙二醛处理作为动脉粥样硬化细胞模型中t-PA促进胆碱能神经元增殖、增加乙酰胆碱的分泌和促进胆碱能神经纤维的数目增多(P0.05)。RT-PCR检测发现t-PA能够激活MMPs,抑制p75NTR-NF-κB信号通路(P0.05)。结论 t-PA激活MMPs反馈抑制p75NTR-NF-κB信号通路增加血管外膜自主神经重构延缓动脉粥样硬化疾病的发生发展。
[Abstract]:Objective to study the effects of tissue type plasminogen activator (t-PA) on p75NTR, inflammatory response, immunomodulation, oxidative stress and intimal hyperplasia. Methods the animal model was established by carotid adventitia stripping in diabetic rabbits, and then the vascular injury was treated with t-PA controlled release microspheres. The changes of nerve remodeling in the control group and the treatment group were observed by immunofluorescence staining, and the effects of t-PA controlled release microspheres on acetylcholine and norepinephrine release were detected. RT-PCR was used to detect the inflammation of t-PA release microspheres on local vascular tissue. Effects of immune response and oxidative stress. Sympathetic neurons were co-cultured with smooth muscle cells and then treated with Glyoxal as atherogenic cell model. T-PA treatment group was used as intervention group to observe the effects of t-PA on the number of cholinergic neurons, the number of synaptic connections with smooth muscle cells and acetylcholine secretion. RT-PCR was used to detect the changes of t 鈮，
本文编号：2512663
[Abstract]:Objective to study the effects of tissue type plasminogen activator (t-PA) on p75NTR, inflammatory response, immunomodulation, oxidative stress and intimal hyperplasia. Methods the animal model was established by carotid adventitia stripping in diabetic rabbits, and then the vascular injury was treated with t-PA controlled release microspheres. The changes of nerve remodeling in the control group and the treatment group were observed by immunofluorescence staining, and the effects of t-PA controlled release microspheres on acetylcholine and norepinephrine release were detected. RT-PCR was used to detect the inflammation of t-PA release microspheres on local vascular tissue. Effects of immune response and oxidative stress. Sympathetic neurons were co-cultured with smooth muscle cells and then treated with Glyoxal as atherogenic cell model. T-PA treatment group was used as intervention group to observe the effects of t-PA on the number of cholinergic neurons, the number of synaptic connections with smooth muscle cells and acetylcholine secretion. RT-PCR was used to detect the changes of t 鈮，
本文编号：2512663
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