【摘要】：目的研究組織型纖溶酶原激活物(t-PA)對(duì)p75NTR、炎性反應(yīng)、免疫調(diào)節(jié)、氧化應(yīng)激的作用,以及對(duì)內(nèi)膜增生的影響。方法對(duì)糖尿病兔給予頸動(dòng)脈外膜剝除建立動(dòng)物模型,然后進(jìn)行血管損傷處理,同時(shí)給予t-PA控釋微球后,免疫熒光染色分別觀察對(duì)照組和處理組神經(jīng)重構(gòu)的變化情況,同時(shí)檢測(cè)給予t-PA控釋微球?qū)σ阴Ｄ憠A和去甲腎上腺素釋放的影響。RT-PCR檢測(cè)t-PA釋控微球?qū)植垦芙M織的炎癥、免疫反應(yīng)和氧化應(yīng)激的影響。采用交感神經(jīng)元與平滑肌細(xì)胞共培養(yǎng),之后給予乙二醛進(jìn)行處理作為動(dòng)脈粥樣硬化細(xì)胞模型,以t-PA處理組作為干預(yù)組,觀察t-PA對(duì)膽堿能神經(jīng)元數(shù)目,與平滑肌細(xì)胞之間的突觸連接數(shù)目、乙酰膽堿分泌的影響。RT-PCR檢測(cè)t-PA-MMP-p75NTR-NF-κB信號(hào)通路的改變。結(jié)果給予t-PA控釋微球能明顯增加膽堿能神經(jīng)元數(shù)目和神經(jīng)纖維(P0.05)而不影響去甲腎上腺素能神經(jīng)元數(shù)目和神經(jīng)纖維(P0.05),并且導(dǎo)致乙酰膽堿釋放增多(P0.05),最終抑制內(nèi)膜增生(P0.05)。離體交感神經(jīng)元與平滑肌細(xì)胞共培養(yǎng),之后給予乙二醛處理作為動(dòng)脈粥樣硬化細(xì)胞模型中t-PA促進(jìn)膽堿能神經(jīng)元增殖、增加乙酰膽堿的分泌和促進(jìn)膽堿能神經(jīng)纖維的數(shù)目增多(P0.05)。RT-PCR檢測(cè)發(fā)現(xiàn)t-PA能夠激活MMPs,抑制p75NTR-NF-κB信號(hào)通路(P0.05)。結(jié)論 t-PA激活MMPs反饋抑制p75NTR-NF-κB信號(hào)通路增加血管外膜自主神經(jīng)重構(gòu)延緩動(dòng)脈粥樣硬化疾病的發(fā)生發(fā)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，

本文編號(hào)：2512663