摘要
目的研究同型半胱氨酸(homocysteinc,Hcy)对帕金森病(PD)模型动物的影响及其机制。方法将63只大鼠随机分成3组,即吡咯烷二硫代氨基甲酸盐(PDTC)组27只、生理盐水对照组27只、假手术组9只。分别在实验前1h腹腔注射PDTC或生理盐水,以后每天1次,连续注射7d,通过脑立体定向注射6-羟多巴胺(6- OHDA)建立大鼠PD模型,2h后同侧脑立体定向注射Hcy或生理盐水,采用TUNEL法、免疫组化技术,选择实验后1d、7d及14d为研究时点,观察黑质多巴胺神经元数量、形态改变,黑质细胞凋亡数,以及黑质细胞NF-κB p65的阳性细胞数的变化。结果(1)局部注射Hcy能明显增加6-OHDA引起的黑质多巴胺神经元变性;(2)局部注射Hcy能明显增加6-OHDA引起的黑质细胞凋亡;(3)局部注射Hcy能明显增加黑质细胞NF-κKB p65阳性细胞数;(4) PDTC可抑制Hcy和(或)6-OHDA引起的NF-κB p65活化,减少黑质细胞凋亡,增加多巴胺神经元数目。结论NF-κB p65的激活是Hcy促进6-OHDA引起的黑质多巴胺神经元变性及黑质细胞凋亡机制中的重要因素之一, PDTC可显著抑制NF-κB p65的活化,多巴胺神经元变性和黑质细胞凋亡。
Objective To study the effects and mechanism of homocysteine （Hey） on Parkinson＇s disease （PD） induced by 6-OHDA in Vivo. Methods 63 rats were divided into 3 groups. With or without a specific inhibitor of NF-κB,PDTC applied,6-OHDA was focally administrated to induce PD and 2h later Hey or 0. 9%NaCl was administrated in the ipsolateral suhstantia nigra. Immunohistochemieal technique was used to observe the number of TH-stained neurons,nigra apoptosis and the changes of the expression of NF-κB on the day 1,7 and 14 after injection. Results After treatment with Hey,the numbers of TH-stained neurons induced by 6-OHDA were decreased,and stantia nigral apoptosis and the expression of NF-κB showed significantly increasing. PDTC significantly inhibited NF-κB activating,decreased stantia nigral apoptosis and increased the TH-positive neurons in the SN compared with saline treatment group （ P〈0. 01）. Conclusion Focal infusion of Hey into the substantia nigra increased the vulnerability of the dopaminergic neurons to 6-OHDA-induced degeneration and apoptosis. The activation of NF-κB may be a crucial mechanism. PDTC attenuated the neurotoxieity of Hey and 6-OHDA.
出处
《中风与神经疾病杂志》
CAS
CSCD
北大核心
2007年第1期56-58,共3页
Journal of Apoplexy and Nervous Diseases
