黄芩苷抑制鱼藤酮帕金森病大鼠黑质铁积聚及作用机制

Inhibition on iron deposition in SN in PD rats by baicalin and its mechanism

目的研究PD大鼠中脑黑质多巴胺(DA)神经损伤、铁积聚、铁转运蛋白表达及氧应激水平改变之间的关系,探讨铁积聚在PD发生发展中的作用及黄芩苷保护DA能神经、抑制铁积聚的机制。方法实验采用鱼藤酮PD模型大鼠,观察黑质铁含量及TH、DMT1、FP1的表达,检测血清、肝脏铁含量以及大脑皮层GSH和MDA含量。结果鱼藤酮PD大鼠DA能神经元明显缺失,同步发生了脑内氧化应激水平增加、GSH降低;血清铁降低而肝铁增高;黑质铁大量积聚发生在DA能神经元大量脱失和铁转运蛋白DMT1、FP1表达改变之后;黄芩苷可调节DMT1、FP1表达,减少黑质铁积聚,降低脑内氧应激水平,增加GSH含量。结论研究证明铁转运蛋白DMT1表达增加和FP1表达降低参与了黑质铁积聚;铁积聚及过高的氧应激反应促进了黑质DA能神经细胞损伤的发展;黄芩苷对PD大鼠DA能神经细胞具有保护作用,机制与抑制铁积聚、调节铁转运蛋白DMT1、FP1表达、降低氧应激有关。

Aim To investigate the relationship between dopaminergic neuronal damage,iron accumulation,expression of iron transporters in SN,and oxidative stress in brain of PD rats to explore mechanism of protection on dopaminergic neurons and inhibition on iron deposition by baicalin.Methods Expressions of TH,DMT1 and FP1,iron content,glutathione（GSH） and malondialdehyde（MDA） in PD rats were detected.Results There was a massive loss of dopaminergic neurons in SN of PD rats,concomitant with increased oxidative stress level.Iron content was lower in serum while higher in liver.Extensive iron deposition in SN occurred after the loss of TH-positive cells and changes of DMT1 and FP1 expression.Baicalin regulated DMT1 and FP1 expression,lessened iron accumulation and oxidative stress level in brain.Conclusions Increased DMT1 and decreased FP1 are involved in iron deposition in SN.Iron accumulation and attendant exorbitant oxidative stress accelerate progression of dopaminergic neuronal damage.Baicalin has protective effect on dopaminergic neurons,and its mechanism is in connection with inhibition on iron deposition,regulation of DMT1 and FP1 expression,and decline in oxidative stress.